GABRD promotes the progression of breast cancer through CDK1-dependent cell cycle regulation
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Curated by eLife
eLife assessment
This study presents a useful finding on the role of GABRD and its downstream target CDK1 in the progression of breast cancer. The evidence supporting the claims of the authors is somewhat incomplete and the elaboration of the mechanistic details on GABARD/CDK1 regulation would have strengthened the study. The work will be of interest to clinicians and biologists working on breast cancer.
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- Evaluated articles (eLife)
- Cancer Biology (eLife)
Abstract
Y-aminobutyric acid (GABA) is an important inhibitory amino acid neurotransmitter that exerts its biological function by binding to GABA receptors, which not only play an important role in neuromodulation, but also involved in regulating the development of tumors. Gamma-aminobutyric acid type A receptor subunit delta ( GABRD ) encodes the δ subunit of GABA A receptor, its impact on breast cancer has not been clearly studied. This study is aiming to reveal the relationship between GABRD and breast cancer development.We performed a tissue microarray to quantify GABRD expression levels in tumor tissue and paracarcinoma tissue. The regulation of GABRD in the proliferation, migration, and apoptosis of breast cancer was examined by a loss-of-function study. A GeneChip microarray was used to probe GABRD for potential downstream molecules. The interaction between GABRD and CDK1 was verified by a set of functional tests and rescue experiments as well as coimmunoprecipitation. GABRD was expressed at significantly higher levels in tumor tissues and was associated with advanced tumor progression. Silencing GABRD resulted in a significant decrease in proliferation and migration and an increase in apoptosis of breast cancer. GABRD regulated the cell cycle by directly interacting with CDK1, which was identified as an important downstream target. GABRD is the breast cancer-related gene and highlights the importance of the GABRD–CDK1 axis in regulating breast cancer proliferation, which provides potential for the development of novel therapeutics.
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eLife assessment
This study presents a useful finding on the role of GABRD and its downstream target CDK1 in the progression of breast cancer. The evidence supporting the claims of the authors is somewhat incomplete and the elaboration of the mechanistic details on GABARD/CDK1 regulation would have strengthened the study. The work will be of interest to clinicians and biologists working on breast cancer.
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Reviewer #1 (Public Review):
Summary:
The paper titled "GABRD promotes the progression of breast cancer through CDK1-dependent cell cycle regulation" investigates the role of GABRD, a subunit of the GABAA receptor, in breast cancer progression and its potential association with CDK1-dependent cell cycle regulation. The study is commendable for shedding light on the role of GABRD in breast cancer, but a few areas can be further improved to enhance the significance and completeness of the research.Strengths:
The study presents valuable insights into the role of GABRD and its potential interaction with CDK1 in breast cancer progression.Recent literature suggests that the neurotransmitter GABA and its receptors play a vital role in regulating various tumors. The paper's innovation lies in revealing GABRD as the most relevant subunit …
Reviewer #1 (Public Review):
Summary:
The paper titled "GABRD promotes the progression of breast cancer through CDK1-dependent cell cycle regulation" investigates the role of GABRD, a subunit of the GABAA receptor, in breast cancer progression and its potential association with CDK1-dependent cell cycle regulation. The study is commendable for shedding light on the role of GABRD in breast cancer, but a few areas can be further improved to enhance the significance and completeness of the research.Strengths:
The study presents valuable insights into the role of GABRD and its potential interaction with CDK1 in breast cancer progression.Recent literature suggests that the neurotransmitter GABA and its receptors play a vital role in regulating various tumors. The paper's innovation lies in revealing GABRD as the most relevant subunit within the GABA receptor family concerning breast cancer and exploring its potential mechanisms in regulating breast cancer progression, including the proposed GABRD-CDK1 axis.
The methods in the study are sufficiently documented to allow replication studies and the quality of the figures and tables is very satisfactory.
In general, this manuscript is well-crafted and addresses a compelling and pertinent topic.
Weaknesses:
The following minor issues should be addressed:1. While the study demonstrates the impact of GABRD expression on patient overall survival, it would be beneficial to supplement this with additional survival indicators. Analyzing other survival metrics, such as disease-free survival or progression-free survival, could provide a more comprehensive understanding of GABRD's clinical relevance in breast cancer.
2. The manuscript alludes to GABRD's regulation of the cell cycle through its interaction with CDK1. Elaborating on the specific binding mechanisms and molecular interactions involved in this regulation would provide a more detailed insight into the proposed GABRD-CDK1 axis.
3. The criteria for high and low expression of GABRD In Table 1 and Fig. 1D should be clearly defined.
4. It would be helpful to explain the reason for classifying the tumor size with 3cm (not 2 or 5cm) in Table 2. It would also be helpful to explain whether the differences in GABRD expression in breast cancer subtypes with different HR and HER-2 expression statuses were analyzed.
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Reviewer #2 (Public Review):
Summary:
The study demonstrated that GABRD was significantly overexpressed in breast cancer tissues and had correlations with disease progression and patient survival rates. When GABRD was downregulated in breast cancer cells, it resulted in reduced cell growth, increased apoptosis, and hindered cell migration and invasion. The study has identified CDK1 as a downstream target of GABRD in mediating its effects on breast cancer. These findings suggest that GABRD is a promising target for therapies related to cell cycle regulation in breast cancer, potentially enhancing the effectiveness of CDK1 inhibitors.Strengths:
The study identifies GABRD as a potential target in breast cancer and provides a new direction for developing breast cancer treatments. The study presents strong clinical correlations of GABARD …Reviewer #2 (Public Review):
Summary:
The study demonstrated that GABRD was significantly overexpressed in breast cancer tissues and had correlations with disease progression and patient survival rates. When GABRD was downregulated in breast cancer cells, it resulted in reduced cell growth, increased apoptosis, and hindered cell migration and invasion. The study has identified CDK1 as a downstream target of GABRD in mediating its effects on breast cancer. These findings suggest that GABRD is a promising target for therapies related to cell cycle regulation in breast cancer, potentially enhancing the effectiveness of CDK1 inhibitors.Strengths:
The study identifies GABRD as a potential target in breast cancer and provides a new direction for developing breast cancer treatments. The study presents strong clinical correlations of GABARD and the functional studies show that CDK1 is a downstream target of GABARD. The in-vivo studies highlight its therapeutic potential for breast cancer.Weaknesses:
The data heavily relies on cell lines and the results lack the mechanistic details on GABARD/CDK1 regulation. -
