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BRD7-Mediated miR-3148 Inhibits Progression of Cervical Cancer by Targeting Wnt3a/β-Catenin Pathway
1Department of Gynaecology, Qinghai University Affiliated Hospital, Xining, 810001, Qinghai, China.
Abstract:
Abnormal expression of miRNAs is closely related to the occurrence and development of tumors, and thus has become the most concerned biomolecule in the field of tumors. But so far, miRNAs that are truly recognized and studied for their function are only a small part, and their mechanism in tumors needs to be further studied. In this study, we identify that miR-3148 is downregulated in the development of cervical cancer. In cervical cancer cells, upregulated miR-3148 inhibits cell proliferation and promotes apoptosis, suggesting that miR-3148 acts as a tumor suppressor gene. Furthermore, we explored the mechanism of miR-3148 in cervical cancer cells from both transcriptional and post-transcriptional levels. Our research reveals that on the one hand, bromodomain containing 7 (BRD7) acts as a transcription factor to up-regulate the expression of miR-3148 at the transcriptional level; on the other hand, miR-3148 targets the 3'UTR of Wnt3a mRNA to inhibit Wnt3a expression at the post-transcriptional level, thereby suppressing Wnt3a/β-catenin signaling pathway and exerting its tumor suppressor role in cervical cancer. In conclusion, our study elucidates the mechanism of BRD7/miR-3148/Wnt3a/β-catenin pathway in cervical cancer and provides a new research direction for targeted therapy of cervical cancer.
Insights
MicroRNA-3148 (miR-3148) acts as a tumor suppressor in cervical cancer by inhibiting cell proliferation and promoting apoptosis. Its expression is regulated by bromodomain containing 7 (BRD7) and it targets Wnt3a, impacting the Wnt3a/β-catenin pathway.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) play crucial roles in tumor development, but their specific functions and mechanisms in many cancers, including cervical cancer, remain incompletely understood.
- Identifying novel miRNAs and elucidating their regulatory pathways are essential for advancing cancer diagnostics and therapeutics.
Purpose of the Study:
- To investigate the role and mechanism of miR-3148 in cervical cancer.
- To identify upstream regulators and downstream targets of miR-3148 in cervical cancer cells.
Main Methods:
- Quantitative real-time PCR to assess miR-3148 expression.
- Cell proliferation assays and apoptosis assays to evaluate the functional role of miR-3148.
- Western blotting and luciferase reporter assays to explore the regulatory mechanism at transcriptional and post-transcriptional levels.
Main Results:
- miR-3148 was found to be downregulated in cervical cancer.
- Upregulation of miR-3148 inhibited cervical cancer cell proliferation and induced apoptosis, confirming its tumor suppressor function.
- Bromodomain containing 7 (BRD7) was identified as a transcriptional activator of miR-3148.
- miR-3148 directly targets Wnt3a mRNA, inhibiting Wnt3a expression and subsequently suppressing the Wnt3a/β-catenin signaling pathway.
Conclusions:
- miR-3148 functions as a tumor suppressor in cervical cancer.
- The BRD7/miR-3148/Wnt3a/β-catenin axis represents a critical regulatory pathway in cervical cancer progression.
- This pathway offers a potential target for novel therapeutic strategies in cervical cancer treatment.
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