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Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
Published on: June 15, 2016
MicroRNA-124 suppresses growth of human hepatocellular carcinoma by targeting STAT3
Yanxin Lu1, Xupeng Yue, Yuanyuan Cui
1Department of Neurobiology, Neuroscience Research Institute, Peking University Health Science Center, Beijing 100191, China; Biomedical Research Institute, Shenzhen-PKU-HKUST Medical Center, Guangdong Province, Shenzhen 518036, China.
Abstract:
The aberrant expression of microRNAs is associated with development and progression of cancers. Down-regulation of miR-124 has been demonstrated in the hepatocellular carcinoma (HCC), but the underlying mechanism by which miR-124 suppresses tumorigenesis in HCC remains elusive. In this study, we found that miR-124 suppresses the tumor growth of HCC through targeting the signal transducers and activators of transcription 3 (STAT3). Overexpression of miR-124 suppressed proliferation and induced apoptosis in HepG-2 cells. Luciferase assay confirmed that miR-124 binding to the 3'-UTR region of STAT3 inhibited the expression of STAT3 and phosphorylated STAT3 proteins in HepG-2 cells. Knockdown of STAT3 by siRNA in HepG-2 cells mimicked the effect induced by miR-124. Overexpression of STAT3 in miR-124-transfected HepG-2 cells effectively rescued the inhibition of cell proliferation caused by miR-124. Furthermore, miR-124 suppressed xenograft tumor growth in nude mice implanted with HepG-2 cells by reducing STAT3 expression. Taken together, our findings show that miR-124 functions as tumor suppressor in HCC by targeting STAT3, and miR-124 may therefore serve as a biomarker for diagnosis and therapeutics in HCC.
Insights
MicroRNA-124 (miR-124) suppresses hepatocellular carcinoma (HCC) growth by targeting STAT3. This study reveals miR-124 as a potential biomarker for HCC diagnosis and therapy.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Aberrant microRNA expression is linked to cancer development and progression.
- Down-regulation of miR-124 is observed in hepatocellular carcinoma (HCC).
- The precise mechanism of miR-124's tumor-suppressive role in HCC is not fully understood.
Purpose of the Study:
- To elucidate the mechanism by which miR-124 suppresses tumorigenesis in HCC.
- To investigate the role of miR-124 in regulating hepatocellular carcinoma cell growth and apoptosis.
- To identify the molecular targets of miR-124 in HCC.
Main Methods:
- Overexpression of miR-124 in HepG-2 cells to assess proliferation and apoptosis.
- Luciferase assays to confirm direct binding of miR-124 to the 3'-UTR of STAT3.
- STAT3 knockdown using siRNA and STAT3 overexpression to validate miR-124's mechanism.
- Xenograft tumor models in nude mice to evaluate miR-124's effect on tumor growth in vivo.
Main Results:
- Overexpression of miR-124 inhibited HepG-2 cell proliferation and induced apoptosis.
- miR-124 directly targets STAT3, reducing both STAT3 and phosphorylated STAT3 expression.
- STAT3 knockdown mimicked miR-124's tumor-suppressive effects, while STAT3 overexpression rescued these effects.
- In vivo, miR-124 suppressed xenograft tumor growth by down-regulating STAT3.
Conclusions:
- miR-124 functions as a tumor suppressor in HCC by targeting STAT3.
- miR-124's mechanism involves the inhibition of STAT3 signaling pathway.
- miR-124 holds potential as a diagnostic biomarker and therapeutic target for HCC.
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