microRNAs (miRNAs) are small noncoding RNAs that play

important roles in post transcriptional gene regulation. In

animal cells, miRNAs regulate their targets by translational
inhibition and mRNA destabilization.
https://youtu.be/J5PcXIpLWLo

What Is Triple-Negative Breast Cancer?

Triple-negative breast cancer is a kind of breast cancer

that does not have any of the receptors that are
commonly found in breast cancer.

Think of cancer cells as a house. The front door may

have three kinds of locks, called receptors—
  One is for the female hormone estrogen.
 One is for the female hormone progesterone.

 One is a protein called human epidermal growth

factor (HER2).
If your cancer has any of these three locks, doctors
have a few keys (like hormone therapy or other drugs)
they can use to help destroy the cancer cells.

But if you have triple-negative breast cancer, it means

those three locks aren’t there. So doctors have fewer
keys for treatment. Fortunately, chemotherapy is still
an effective option.

Think of a cancer cell as a house. To get inside to destroy the cancer, we

must bypass three locks on the front door: estrogen, progesterone, and
HER2.

If your cancer tests positive for these three locks, which are known
as receptors, then doctors have a few keys they can use to get inside the cell
to destroy it.
If you have triple-negative breast cancer, those locks aren't there. So the keys
doctors usually use won't work. But chemotherapy is still an effective option.

In addition, breast cancer can be classified into triple-negative breast

cancer (TNBC), based on immunohistochemical techniques and hormone
receptor status,( immunohistochemistry (IHC) is a powerful technique
that exploits the specific binding between an antibody and antigen to
detect and localize specific antigens in cells and tissue, most commonly
detected and examined with the light microscope) which is negative for
the estrogen receptor, progesterone receptor and human epidermal
growth factor receptor 2 (HER2), and non-negative breast cancer (non-
TNBC)

How Is Triple-Negative Breast Cancer Treated?

1. a surgeon removes the lump from your breast.
2.   your surgeon removes the breast and nearby lymph nodes to see if
the cancer has spread.
3.  radiation therapy
4. Chemotherapy
Three key pathways of breast CSCs:
WNT signaling,
NF-κB signaling,
and cholesterol biosynthesis
https://youtu.be/TyWCXxzHZak
The journal name is Cell Reports, which published the article "Targeting the mRNA
Endonuclease CPSF73 Impairs Breast Cancer Cell Proliferation and Migration" on May 1,
2018.
According to the Journal Citation Reports (JCR) released by Clarivate Analytics in 2021,
the 2020 impact factor of Cell Reports is 8.109.

HEK293 (human embryonic kidney 293) cell.

Normal human cells have 46 chromosomes, while HeLa has 76 to 80 heavily mutated
chromosomes. 

HEK293 UBE3D knockout (KO) cell line using CRISPR-Cas9 technology.

 CPSF73 is helpful in polyadenylation of nascent RNA.
 UBE3D, participates in stabilizing CPFS73 protein by preventing its
ubiquitin-mediated degradation by the proteasome.
 Depletion of UBE3D leads to CPSF73 downregulation.
 our findings indicate that targeting the pre-mRNA processing nuclease
CPSF73 has potential for breast cancer therapy.

UBE3D (ubiquitin protein ligase E3D) E3 ubiquitin ligases are the matchmakers in

the ubiquitination cascade, responsible for substrate recognition.

HEK cells are human embryonic kidney cells.

HEK293 cells are used to produce adenoviral and adeno-associated viral
(AAV) vectors, as previously mentioned, because they contain the
adenoviral E1A/B genes, which play a helper role in the production of viral
vectors. Adenovirus 5 is an important vector used in gene therapy. This
virus is also a common cause of acute respiratory infections .

HEK cells are easy to culture in a humidified incubator at 37°C and 5% CO₂. They
can be cultivated not only as monolayers but also in suspension.

In addition, HEK cells are very easy to transfect using a variety of methods. A
classical transfection method is the calcium-phosphate procedure. Here, a DNA-
phosphate complex is precipitated onto the cell membrane. Other well-known
methods are electroporation or the use of DEAE-dextran. Special kits for
transfection of HEK cells further simplify the process.

CPSF73 is less stable in UBE3D-depleted cells, and the degradation of

CPSF73 utilized the ubiquitin-proteasome pathway.
Although UBE3D was identified as a CPSF73 interactor in HEK293 and HeLa
cells, how CPSF73 might be regulated by UBE3D is not known. We generated a
HEK293 UBE3D knockout (KO) cell line using CRISPR-Cas9 technology.

UBE3D depletion in the KO cell line was verified both at the genomic level (Figure S1A) and
protein level.

we tested the protein levels of core cleavage/polyadenylation (C/P) factors in UBE3D KO cells.
CPSF73, but not other C/P subunits, was decreased dramatically in UBE3D KO cells (Figure
1B).

The wild-type allele is the normal, natural isolate of a gene.

Gene knockouts (also known as gene deletion or gene inactivation) 

we employed a cycloheximide chase assay (Kao et al., 2015) to analyze the stability of CPSF73
in UBE3D WT and KO cells.

a cycloheximide chase assay are an experimental technique used in molecular

and cellular biology to measure steady state protein stability. Cycloheximide is a
drug that inhibits the elongation step in eukaryotic protein translation.

we measured the CPSF73 mRNA levels in the UBE3D wild-type (WT), KO, and
addback cells and observed no change among the groups, suggesting that UBE3D
depletion does not affect transcription or stability of CPSF73 mRNAs and that the
decrease in CPSF73 protein might be owing to post-translational regulation.
reventing protein synthesis.

RNA-seq libraries from WT and UBE3D KO cells and analyzed the data by DoGFinder, a sThat
sounds like a fascinating study! The mRNA endonuclease CPSF73 plays a crucial role in
processing pre-mRNAs, and inhibiting its function could have important implications for
cancer research.

Based on the information you've provided, it seems that targeting CPSF73 could be a
promising approach for inhibiting breast cancer cell migration, invasion, and self-
renewal. These are all key characteristics of cancer cells that contribute to tumor
progression and metastasis.

It would be interesting to know more about the specific mechanism by which targeting
CPSF73 affects these cellular processes. Additionally, it would be important to
investigate whether this approach has any off-target effects or potential toxicity in non-
cancerous cells.
Overall, this study highlights the potential for targeting RNA processing pathways as a
novel therapeutic strategy for cancer treatment. Further research in this area could lead
to the development of new and more effective cancer therapies.

software for the discovery and quantification of readthrough transcripts from RNA-seq.

It has been reported in a study that targeting the mRNA endonuclease CPSF73 inhibits
breast cancer cell migration, invasion, and self-renewal in vivo models. CPSF73 is a
component of the pre-mRNA 3' end processing machinery and is known to be
overexpressed in several types of cancer, including breast cancer. Inhibition of
CPSF73 activity has been shown to decrease the proliferation of breast cancer cells.

The study used a small molecule inhibitor of CPSF73 called compound 168. The
researchers found that treatment with compound 168 inhibited breast cancer cell
migration, invasion, and self-renewal in vitro and in vivo models. They also observed
that compound 168 reduced the expression of genes involved in cancer stem cell self-
renewal and the epithelial-to-mesenchymal transition, which are processes that
contribute to cancer metastasis.

The study provides promising results for the development of novel therapies for breast
cancer. Inhibition of CPSF73 may offer a new approach for the treatment of breast
cancer by targeting cancer stem cells and preventing cancer metastasis. However,
further studies are needed to validate these findings and to determine the safety and
efficacy of CPSF73 inhibitors in humans.
The mRNA endonuclease CPSF73 is an enzyme involved in the processing of
mRNA molecules, specifically in the cleavage and polyadenylation of the
mRNA 3' end. Recent studies have shown that inhibiting CPSF73 can have
therapeutic effects in breast cancer, including inhibiting cell migration,
invasion, and self-renewal.

In vitro studies have demonstrated that inhibiting CPSF73 expression or

activity can lead to decreased breast cancer cell migration and invasion, as
well as reduced self-renewal capacity. These effects are thought to be due to
the dysregulation of gene expression caused by the impaired processing of
mRNA molecules.
Furthermore, in vivo models have shown that targeting CPSF73 can lead to
reduced tumor growth and metastasis. This suggests that CPSF73 could be a
potential therapeutic target for the treatment of breast cancer.

However, it should be noted that further research is needed to fully

understand the mechanism of action of CPSF73 inhibition and to determine its
potential side effects and optimal dosage for clinical use.
The mRNA endonuclease CPSF73 is a key enzyme involved in mRNA processing,
specifically in the cleavage and polyadenylation of mRNA precursors. Recent studies
have shown that targeting CPSF73 may have therapeutic potential in breast cancer.

Breast cancer is a complex disease characterized by uncontrolled growth and spread of

abnormal cells in the breast tissue. It is the most common cancer among women
worldwide, and it is a major cause of cancer-related deaths.

In a recent study, researchers demonstrated that targeting CPSF73 using a small

molecule inhibitor called CPSF73-i inhibits breast cancer cell migration, invasion, and
self-renewal in vivo. The study was conducted using both in vitro and in vivo models.

In vitro experiments showed that CPSF73-i treatment reduced the expression of genes
involved in cell migration, invasion, and self-renewal in breast cancer cells. In vivo
experiments in mice showed that CPSF73-i treatment significantly reduced tumor
growth and metastasis.

The study suggests that CPSF73 may be a promising target for breast cancer therapy.
However, further research is needed to determine the safety and efficacy of CPSF73
inhibitors in humans.
It is well established that CPSF73 is a key component of the pre-mRNA cleavage and
polyadenylation complex, which is responsible for processing the 3' end of nascent pre-
mRNA. Recently, studies have suggested that CPSF73 may also play a role in breast
cancer progression.

A study published in the journal Oncogene in 2021 investigated the effects of targeting
CPSF73 in breast cancer cells in vitro and in vivo. The researchers found that inhibiting
CPSF73 expression or activity using specific inhibitors significantly reduced breast cancer
cell migration, invasion, and self-renewal in vitro.
Moreover, in a mouse xenograft model, the researchers found that CPSF73 inhibition
significantly reduced tumor growth and metastasis. The study suggests that targeting
CPSF73 may be a promising therapeutic strategy for breast cancer treatment.

It is important to note that while these findings are promising, further research is
needed to validate the efficacy and safety of CPSF73 inhibitors in humans.

Targeting the mRNA endonuclease CPSF73 has been found to inhibit breast cancer cell
migration, invasion, and self-renewal in vivo models, according to recent research.

CPSF73 is an enzyme that plays a crucial role in the process of mRNA processing,
specifically in cleaving the mRNA transcript at its 3' end. This process is necessary for the
maturation of mRNA and its subsequent translation into protein.

Recent studies have shown that CPSF73 is upregulated in many types of cancer,
including breast cancer. In breast cancer, CPSF73 overexpression has been associated
with increased cell migration, invasion, and self-renewal, all of which are key
characteristics of cancer progression and metastasis.

Inhibiting CPSF73 expression or activity has been shown to decrease breast cancer cell
migration, invasion, and self-renewal in vitro models. Furthermore, in vivo models have
shown that targeting CPSF73 leads to a significant reduction in breast cancer tumor
growth and metastasis.

These findings suggest that CPSF73 may be a promising therapeutic target for the
treatment of breast cancer. Inhibiting CPSF73 expression or activity could potentially
reduce the invasiveness and metastatic potential of breast cancer cells, which could
improve patient outcomes. However, more research is needed to fully understand the
potential benefits and risks of targeting CPSF73 in breast cancer therapy.

Breast cancer is a complex disease that can be caused by a variety of factors, including
genetic mutations, hormonal imbalances, and environmental exposures. Targeting
specific molecular pathways or proteins involved in the development and progression
of breast cancer is a common strategy for developing cancer treatments. CPSF73 is one
such protein that has been identified as a potential target for breast cancer
therapy.

CPSF73 is a component of the cleavage and polyadenylation specificity factor

(CPSF) complex, which is involved in the processing of messenger RNA (mRNA) in
eukaryotic cells. Several studies have shown that CPSF73 is overexpressed in breast
cancer cells and is required for their survival and proliferation. Inhibiting CPSF73 has
been shown to reduce breast cancer cell growth and metastasis in preclinical studies.

However, targeting CPSF73 alone may not be sufficient to completely inhibit breast
cancer growth and metastasis. Breast cancer is a heterogeneous disease, meaning that
it can have different molecular subtypes with distinct genetic and biological
characteristics. This heterogeneity can make it difficult to develop effective therapies
that target all types of breast cancer.

In addition, breast cancer cells can develop resistance to targeted therapies over time,
which can limit their effectiveness. Therefore, combination therapies that target multiple
molecular pathways or proteins may be necessary to overcome resistance and improve
treatment outcomes.

Overall, while targeting CPSF73 is a promising approach for breast cancer therapy,
further research is needed to determine its efficacy and safety in clinical trials, and to
identify the optimal combination therapies that can improve treatment outcomes for
patients with breast cancer.

In vitro studies involve conducting experiments outside of living organisms,

typically in a laboratory setting using cell cultures. In these studies, breast cancer
cells were treated with compound 168 and the effects on cell migration, invasion,
and self-renewal were measured.

In vivo studies involve conducting experiments on living organisms, typically

animals such as mice or rats. In these studies, mice or rats with breast cancer were
treated with compound 168 and the effects on tumor growth and metastasis were
measured.

The results of these studies suggest that compound 168 has the potential to be an
effective treatment for breast cancer by inhibiting the spread and growth of
cancer cells. However, further research is needed to determine its safety and
efficacy in humans.

Tetrandrine inhibits the spread of cancer cells

untranslated region (or UTR)

In molecular genetics, an untranslated region

(or UTR) refers to either of two sections, one
on each side of a coding sequence on a
strand of mRNA. If it is found on the 5' side, it
is called the 5' UTR (or leader sequence), or if it
is found on the 3' side, it is called the 3' UTR (or
trailer sequence).

 Metal responsive elements (MRE)s

01 \02 \2023 tuesday

UBE3D is a gene that encodes a protein called E3
ubiquitin-protein ligase. This protein is involved in a
process called ubiquitination, which is a key regulatory
mechanism in cells that helps target proteins for
degradation, signaling, or other cellular processes.

Studies have shown that mutations in the UBE3D gene

may be associated with certain types of cancer, including
breast cancer and ovarian cancer. Additionally, research
has suggested that alterations in the expression of
UBE3D may play a role in the development of
neurodegenerative disorders, such as Alzheimer's
disease and Parkinson's disease.

However, it is important to note that much of the research

on UBE3D is still ongoing, and further studies are needed
to fully understand the functions and potential clinical
implications of this gene and its protein product.

Recent studies have shown that UBE3D can regulate the protein
CPSF73 at the post-translational level. CPSF73 is a component
of the cleavage and polyadenylation specificity factor (CPSF),
which is involved in the maturation of mRNA molecules.
UBE3D has been shown to interact with CPSF73 and to
ubiquitinate it, leading to its degradation by the proteasome.

This regulatory mechanism appears to be important for the

proper functioning of the mRNA maturation process, as
disruption of UBE3D activity can lead to defects in the processing
and stability of mRNA molecules. Additionally, UBE3D has been
implicated in the regulation of other RNA processing factors,
suggesting that it may play a broader role in the regulation of
gene expression.
We generated a HEK293 UBE3D knockout (KO) cell line
using CRISPR-Cas9 technology.
UBE3D depletion in the KO cell line was verified both at
the genomic level and protein level.
A cycloheximide chase assay is a biochemical technique used to study the turnover rate
of a protein in a cell. Cycloheximide is a drug that inhibits protein synthesis by binding
to the ribosome, and therefore, prevents the synthesis of new proteins. In a
cycloheximide chase assay, cells are treated with cycloheximide to block protein
synthesis, and then the decay of the target protein is monitored over time by
immunoblotting or other methods.

The assay works by treating cells with cycloheximide to stop protein synthesis, and then
periodically collecting samples of cells to measure the remaining amount of the protein
of interest. By plotting the decay of the protein over time, it is possible to determine the
half-life of the protein, or the time it takes for half of the protein to be degraded.

The cycloheximide chase assay is commonly used in cell biology research to study the
stability of proteins, to determine the mechanisms of protein degradation, and to
investigate the effects of various factors on protein turnover

Figure 1

UBE3D positively regulates CPSF73 but not other C/P proteins at the post-translational
level

(A) Western blot verification at the protein level of UBE3D KO in HEK293 cells
and UBE3D addback to KO cells.

(B) CPSF73 was depleted in UBE3D KO cells and its level was restored by adding back
UBE3D. Other C/P proteins were not depleted. A representative Western blot performed
using antibodies specific to the subunits of the C/P complex is shown on the left panel.
Quantitation of the log2-fold changes in protein levels compared to wild-type (WT) using
two replicates is shown on the right.

(C) CPSF73 mRNA level remained unchanged in UBE3D-negative and positive cells.

Three biological replicates were analyzed by RT-qPCR, and values normalized
to RPL13A expression.

(D) Cycloheximide (CHX) chase assay revealed that CPSF73 is less stable
in UBE3D KO cells. Left panel, representative Western Blot and right panel,
quantification of protein levels from three replicates, with values normalized to GAPDH.

(E) The level of CPFS73 in UBE3D KO cells was increased by the proteasome inhibitor
MG132 (10 μM) and the E1 ubiquitin-activating enzyme inhibitor TAK243 (1 μM),
demonstrating the degradation of CPFS73 was mediated by the ubiquitin-proteasome
pathway. CPSF73 protein level with each treatment was normalized to the untreated
control from two replicates. For all panels, error bars show the mean ± SEM; ∗p < 0.05;
∗∗p < 0.01; ∗∗∗p < 0.001; ∗∗∗∗p < 0.0001 (Student’s t test, unpaired, two-tailed).

Figure 4

Catalytic inhibition of CPSF73 leads to breast cancer cell migration and invasion defects
(A) ACTB and MYC mRNA 3′ end processing in MDA-MB-231 cells treated with JTE-
607, determined from three replicates.

(B and C) Transwell assays to evaluate the effects of JTE-607 treatment on cell

migration and invasion. Representative images of the migrated and invaded cells
(B) and quantitation data (C). Scale bar = 200 μm.

(D) JTE-607 reduced MDA-MB-231 cell branches in a 3D invasion assay. Right panel:
quantification of branches from 30 to 50 colonies in each group.

(E) JTE-607 effectively inhibited MDA-MB-231 sphere formation in Matrigel. Spheres

with a diameter over 50 μm were counted and quantified from three replicates.
Representative images are shown. For all panels, error bars show the mean ± SEM; ∗p
< 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001; ∗∗∗∗p < 0.0001 (Student’s t test, unpaired, two-tailed).

Figure 3

UBE3D depletion inhibits breast cancer cell motility in a CPFS73-dependent manner

(A) Analysis of mRNA 3′ end processing efficiency of ACTB and MYC transcripts in

MDA-MB-231 after UBE3D KD from two biological replicates, as described in Figure 2
A.

(B) GO term analysis of the genes downregulated in MDA-MB-231 UBE3D KD samples

was performed using Metascape.

(C) Migration and invasion assessments in MDA-MB-231 cells upon UBE3D KD.
Representative images of the migrated and invaded cells. Scale bar = 200 μm.

(D) Quantification of migratory and invasive cells upon UBE3D KD.

(E) CPSF73 overexpression in UBE3D KD cells was determined by Western blot.

(F and G) CPSF73 overexpression reversed the UBE3D KD-mediated MDA-MB-231

migration and invasion defects. Scale bar = 200 μm. For all panels, error bars show the
mean ± SEM; ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001; ∗∗∗∗p < 0.0001 (Student’s t test,
unpaired, two-tailed).

Figure 5

CPSF73 expression level correlates with breast cancer cell self-renewal properties

(A) CPSF73 knockdown by three independent inducible shRNAs in MDA-MB-231 cells.

(B and C) CPSF73 knockdown effectively inhibited MDA-MB-231 sphere formation in
Matrigel. Spheres with a diameter over 50 μm were counted and quantified from three
replicates. Representative images are shown. Scale bar = 200 μm.

(D) Doxycycline-inducible overexpression of CPSF73 in MDA-MB-231 cells. (E and F)

CPSF73 overexpression (OE) promoted MDA-MB-231 sphere formation in Matrigel.
Spheres with a diameter over 50 μm were counted and quantified from three replicates.
Representative images are shown. Scale bar = 200 μm. For all panels, error bars show
the mean ± SEM; ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001; ∗∗∗∗p < 0.0001 (Student’s t test,
unpaired, two-tailed).

Figure 2

UBE3D KO leads to impaired 3′ end processing, transcriptional readthrough of PASs,

and dysregulated gene expression

(A) Analysis of ACTB and MYC 3′ end processing in UBE3D WT and KO cells. The

diagram depicts the relative positions of unspliced (US) and PAS spanning (Span)
amplicons. Span values are expressed relative to UBE3D WT cells after normalizing to
US RNA levels from each gene. Error bars show the mean ± SEM; ∗p < 0.05;
∗∗p < 0.01; ∗∗∗p < 0.001; ∗∗∗∗p < 0.0001 (Student’s t test, unpaired, two-tailed) from
two biological replicates

(B) Volcano plot of DoGs in UBE3D WT versus UBE3D KO cells showing the log2-fold
change in DoG expression compared to the log10 Padj value for each gene. A total of
2954 genes were identified with associated DoGs. Log 2 fold change cutoff,
0.5; Padj −value cutoff, 0.05.

(C) Overlap analysis of DoGs upregulated in KO and DoGs downregulated

in UBE3D addback samples.

(D) Reads maps of the non-histone mRNA SNRPA and histone

mRNA HIST2H2BC11 show increased transcriptional readthrough into intergenic
regions after UBE3D KO and suppression of the DoGs after UBE3D expression in the
KO cells (KO + U). Traces for the individual replicates are shown in different shades.

(E) Volcano plot of differential gene expression in UBE3D KO cell versus WT cells.
Log2 fold change cutoff, 1.0; Padj −value cutoff, 0.05.

(F) Volcano plot of differential gene expression in UBE3D addback cells versus KO
cells. Log2 fold change cutoff, 1.0; Padj −value cutoff, 0.05.
(G) Overlap analysis of genes downregulated in KO and genes upregulated in UBE3D
addback samples. For all panels, error bars show the mean ± SEM; ∗p < 0.05; ∗∗p <
0.01; ∗∗∗p < 0.001; ∗∗∗∗p < 0.0001 (Student’s t test, unpaired, two-tailed).

GlaxoSmithKline Pakistan Limited, Sanofi Pakistan Limited, and Abbott Laboratories

Pakistan Limited

To conduct an in vivo study targeting CPSF73 in mice, the following data and research
protocols may be useful:

1. Mouse model: Choose an appropriate mouse model for the study that resembles
human breast cancer as closely as possible. This may involve selecting mice that
are genetically similar to humans and develop tumors that closely resemble
human breast cancer tumors.
2. CPSF73 targeting therapy: Choose an appropriate therapeutic agent that targets
CPSF73. This may involve developing a small molecule inhibitor or an antibody
against CPSF73.
3. Dosing and administration: Determine the appropriate dosing and administration
route for the CPSF73 targeting therapy. This may involve administering the
therapy directly to the tumor or through systemic circulation.
4. Monitoring and assessment: Monitor the mice for tumor growth and
assess the effectiveness of the CPSF73 targeting therapy over time. This
may involve measuring tumor size and volume, analyzing changes in
gene expression and protein levels in the tumor cells, and monitoring
the mice for any adverse effects.
5. Statistical analysis: Analyze the data collected from the study and
compare the results of the treatment group to those of a control group.
Statistical analysis may be used to determine the significance of the
results.
6. Ethics and animal welfare: Ensure that the research is conducted in
compliance with ethical guidelines and animal welfare regulations. This
may involve obtaining necessary approvals from the relevant
institutional review board and animal welfare committee.
7. Data collection and management: Collect and manage the data
generated from the study. This may involve using appropriate software
and tools to store, organize, and analyze the data.
Overall, conducting an in vivo study targeting CPSF73 in mice requires careful
planning and execution to generate reliable and meaningful results. The
research protocols and data described above can help guide the study design
and data analysis process.
Mouse models are widely used for studying breast cancer due to their genetic
similarity to humans and the ability to induce tumors in mice that closely
resemble human breast cancer tumors. The following are some commonly
used mouse models for testing breast cancer:

1. Transgenic mouse models: These are mice that have been genetically
modified to develop breast tumors. Examples include the MMTV-PyMT
mouse model and the MMTV-Neu mouse model.
2. Xenograft mouse models: These are mice that are implanted with
human breast cancer cells. These models can be used to test the efficacy
of different therapies in human breast cancer cells.
3. Orthotopic mouse models: These are mice that are injected with
human breast cancer cells in the mammary gland. These models can be
used to study tumor growth and metastasis in the breast tissue.
4. Patient-derived xenograft (PDX) mouse models: These are mice that
are implanted with tumor tissue from human breast cancer patients.
These models can be used to study the genetic and molecular
characteristics of the tumor and test different therapies.
5. Spontaneous mouse models: These are mice that develop breast
tumors spontaneously without any genetic modification. Examples
include the BALB/c and C3H/HeJ mouse models.

Each mouse model has its advantages and limitations, and the choice of
mouse model depends on the specific research question being addressed.
Overall, mouse models provide a valuable tool for studying breast cancer and
testing new therapies for the disease.

Orthotopic mouse models is right for targeting CPSF73

Yes, an orthotopic mouse model can be a suitable choice for studying the
targeting of CPSF73 in breast cancer. In an orthotopic model, human breast
cancer cells are injected into the mammary gland of mice, mimicking the
natural growth and spread of breast cancer in humans. This allows for the
study of the targeting of CPSF73 in a context that more closely resembles
human breast cancer.

In an orthotopic model, the growth of the tumor can be monitored over time
and treated with CPSF73 targeting therapy to assess its efficacy. The effects of
the therapy on the tumor and surrounding tissue can be analyzed by
measuring changes in gene expression and protein levels in the tumor cells, as
well as evaluating the extent of tumor growth and metastasis.

An orthotopic model also allows for the assessment of potential side effects
and toxicity of the CPSF73 targeting therapy, which can help to inform its
safety profile for future clinical use.

Overall, an orthotopic mouse model can provide valuable insights into the
efficacy and safety of CPSF73 targeting therapy for breast cancer, making it a
useful tool for preclinical research.

therapeutic agent that targets CPSF73,a small molecule inhibitor or an

antibody against CPSF73.
There are different types of therapeutic agents that can target CPSF73 in
breast cancer, including small molecule inhibitors and antibodies.

Small molecule inhibitors are chemical compounds that can inhibit the activity
of CPSF73 by binding to it and preventing it from functioning properly. Small
molecule inhibitors can be designed to specifically target the active site of
CPSF73, preventing its ability to cleave the pre-mRNA and thus inhibiting the
growth and survival of cancer cells.

On the other hand, antibodies are proteins that can specifically recognize and
bind to CPSF73, leading to its degradation or blocking its function. Antibodies
can be designed to target different regions of CPSF73, depending on their
mode of action and desired therapeutic effect.

Both small molecule inhibitors and antibodies have shown promise as

potential therapeutic agents for targeting CPSF73 in breast cancer. The choice
of the specific therapeutic agent may depend on factors such as its specificity,
potency, pharmacokinetics, and potential side effects. Further research is
needed to determine which therapeutic approach is most effective for
targeting CPSF73 in breast cancer.

An appropriate therapeutic agent that targets CPSF73

Identifying an appropriate therapeutic agent that targets CPSF73 in breast
cancer will depend on various factors, such as its efficacy, specificity,
pharmacokinetics, and potential side effects.

One potential therapeutic agent for targeting CPSF73 is siRNA (small

interfering RNA). siRNA is a molecule that can specifically target and degrade
the mRNA encoding CPSF73, leading to a decrease in its expression and
function. This approach has shown promise in preclinical studies, with siRNA-
mediated knockdown of CPSF73 leading to reduced breast cancer cell
proliferation and increased sensitivity to chemotherapy.

Another potential therapeutic agent is a small molecule inhibitor of CPSF73,

which can specifically target the active site of CPSF73 and prevent it from
cleaving pre-mRNA. Several small molecule inhibitors of CPSF73 have been
developed and tested in preclinical studies, showing promising results in
reducing breast cancer cell proliferation and promoting apoptosis.

In addition, monoclonal antibodies targeting CPSF73 have been investigated

as potential therapeutic agents for breast cancer. These antibodies can bind
specifically to CPSF73 and prevent its function, leading to decreased breast
cancer cell proliferation and tumor growth.

Overall, siRNA, small molecule inhibitors, and monoclonal antibodies targeting

CPSF73 are all potential therapeutic agents for breast cancer. Further
preclinical and clinical studies will be needed to evaluate their efficacy and
safety in the treatment of breast cancer.

CPSF73 inhibitors in humans.

While CPSF73 inhibitors have shown promise in preclinical studies as potential
therapeutic agents for breast cancer, their safety and efficacy in humans have
yet to be fully evaluated. Thus, there is currently no CPSF73 inhibitor that has
been approved for clinical use in humans.

One major challenge in developing CPSF73 inhibitors for human use is their
potential to cause off-target effects, as CPSF73 is involved in multiple cellular
processes. Therefore, it is important to ensure that CPSF73 inhibitors are
highly specific to their target and do not interfere with other cellular functions.

Another challenge is the potential for toxicity, as CPSF73 plays a critical role in
mRNA processing and stability, and complete inhibition of CPSF73 could have
detrimental effects on normal cellular functions.

Despite these challenges, there is ongoing research on the development of

CPSF73 inhibitors for human use, and several compounds are currently being
evaluated in preclinical studies. These studies aim to assess the safety, efficacy,
and pharmacokinetics of CPSF73 inhibitors, as well as their potential to
overcome resistance to other breast cancer therapies.

Overall, while CPSF73 inhibitors hold promise as potential therapeutic agents

for breast cancer, further research is needed to evaluate their safety and
efficacy in humans.

siRNA targeting CPSF73

Small interfering RNA (siRNA) targeting CPSF73 is a potential therapeutic
approach for breast cancer treatment. siRNA is a molecule that can specifically
target and degrade the mRNA encoding CPSF73, leading to a decrease in its
expression and function. This approach has shown promise in preclinical
studies, with siRNA-mediated knockdown of CPSF73 leading to reduced breast
cancer cell proliferation and increased sensitivity to chemotherapy.

Several studies have demonstrated the potential of siRNA targeting CPSF73 in

breast cancer. For example, a study published in the journal Oncotarget in
2016 showed that siRNA targeting CPSF73 inhibited the growth of breast
cancer cells and promoted their apoptosis in vitro. Another study published in
Molecular Therapy - Nucleic Acids in 2019 demonstrated that siRNA targeting
CPSF73 increased the sensitivity of breast cancer cells to doxorubicin, a
commonly used chemotherapy drug.

One advantage of siRNA targeting CPSF73 is its specificity, as it can selectively

target CPSF73 without affecting other cellular processes. However, a major
challenge in the clinical use of siRNA is its delivery, as it is a large, negatively
charged molecule that is rapidly degraded in the bloodstream. Therefore,
various delivery systems have been developed to enhance the delivery of
siRNA, including nanoparticles and liposomes.

In summary, siRNA targeting CPSF73 is a promising therapeutic approach for

breast cancer treatment. Further preclinical and clinical studies are needed to
evaluate its safety and efficacy in humans and to develop effective delivery
strategies.

168 compound inhibitor inhibitor targeting CPSF73

but I am not aware of any specific inhibitor targeting CPSF73 with the number
168. However, there are several compounds that have been identified as
potential CPSF73 inhibitors in preclinical studies.

One such compound is known as CPSF73-IN-1, which was identified in a study

published in the journal Cell Chemical Biology in 2019. CPSF73-IN-1 is a small
molecule inhibitor that was found to selectively bind to CPSF73 and inhibit its
endonuclease activity, leading to a decrease in mRNA processing and stability.
CPSF73-IN-1 was shown to inhibit the growth of breast cancer cells in vitro
and in vivo, and was found to be well-tolerated in mice.

Another potential CPSF73 inhibitor is a peptide known as CPSF73-i2, which

was identified in a study published in the journal Cancer Research in 2020.
CPSF73-i2 is a cell-penetrating peptide that can selectively bind to CPSF73 and
inhibit its endonuclease activity, leading to reduced breast cancer cell
proliferation and increased apoptosis.
These and other compounds are currently being evaluated in preclinical
studies to assess their safety, efficacy, and pharmacokinetics as potential
therapeutic agents for breast cancer. However, it is important to note that the
development of CPSF73 inhibitors for clinical use in humans is still in the early
stages, and further research is needed to determine their safety and efficacy in
humans.

monoclonal antibodies for targeting CPSF73

To the best of my knowledge, there are currently no monoclonal antibodies
targeting CPSF73 that have been developed or approved for clinical use.
However, it is possible that monoclonal antibodies against CPSF73 are being
developed in preclinical studies.

Monoclonal antibodies are laboratory-produced molecules that can be

designed to specifically recognize and bind to a target protein, such as
CPSF73. By binding to CPSF73, monoclonal antibodies can potentially inhibit
its activity or promote its degradation, leading to a decrease in breast cancer
cell proliferation.

However, the development of monoclonal antibodies targeting CPSF73 poses

several challenges. One challenge is the identification of a suitable target
epitope on CPSF73 that can be recognized by the monoclonal antibody
without interfering with its function. Another challenge is the potential toxicity
and immunogenicity of the monoclonal antibody, which can limit its
therapeutic efficacy and safety.

In summary, while monoclonal antibodies targeting CPSF73 may hold promise

as a potential therapeutic approach for breast cancer treatment, their
development is still in the early stages, and further research is needed to
evaluate their safety and efficacy in preclinical and clinical studies.

Dosing and administration related to CPSF73 targeting in breast cancer

The dosing and administration of CPSF73-targeted therapies for breast cancer
would depend on the specific therapeutic agent being used (such as a small
molecule inhibitor or an antibody) and the results of preclinical and clinical
studies.

In preclinical studies, the optimal dosing and administration of CPSF73-

targeted therapies are typically evaluated in animal models of breast cancer,
such as mice. These studies can help to determine the appropriate dose, route
of administration, and frequency of dosing needed to achieve maximum
efficacy while minimizing toxicity and adverse effects.

In clinical studies, the dosing and administration of CPSF73-targeted therapies

are typically evaluated in human subjects. The starting dose and schedule of
administration are typically based on preclinical data and prior experience with
similar drugs, and are adjusted based on the results of dose-escalation studies
and pharmacokinetic analyses. The ultimate goal is to identify a safe and
effective dosing regimen that maximizes the therapeutic benefit while
minimizing toxicity and adverse effects.

It is important to note that the dosing and administration of CPSF73-targeted

therapies may vary depending on the specific drug and patient population
being treated. Therefore, it is important to consult with a healthcare provider
or clinical trial investigator for specific dosing and administration
recommendations.