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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
MiR-142 inhibits the development of cervical cancer by targeting HMGB1
Daqiong Jiang1, Huiyan Wang2, Zhuyan Li1
1Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan 430071, Hubei, P.R. China.
Abstract:
It has been reported that miRNAs is deregulated in diverse human cancers, involving human cervical cancer. However, the clinical significances and potential mechanisms of miR-142 in the development and progression of cervical cancer were not elucidated completely till now. In this study, we found that the expression of miR- 142 was obviously down-regulated in human cervical cancer tissues and a panel of cell lines. According to statistics, the expression of miR-142 was negatively related to advanced FIGO stage and lymphatic metastasis (p < 0.001). Furthermore, our functional analysis revealed the overexpression of miR-142 affected cell proliferation and invasiveness, and enhanced cell apoptosis in representative SiHa and HeLa cells. Based on the molecular level, our findings showed the 3' untranslated region (3'-UTR) of high-mobility group box 1 protein (HMGB1) was a direct target of miR-142, and determined an inverse correlation with the expression of miR-142. Ectopic expression of HMGB1 could attenuate the inhibitory impact of miR-142 on the proliferation and invasiveness of cervical cancer cells. In conclusion, the present work suggested that miR-142 affects cervical cancer cell proliferation and invasiveness, and enhances cell apoptosis via directly targeting the expression of HMGB1, and these findings may lay a novel foundation for the promising therapy target of cervical cancer.
Insights
MicroRNA-142 (miR-142) is downregulated in cervical cancer, correlating with advanced stages and metastasis. Restoring miR-142 inhibits cancer cell growth and invasion by targeting HMGB1, suggesting miR-142 as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are implicated in various human cancers, including cervical cancer.
- The precise roles and mechanisms of miR-142 in cervical cancer progression remain unclear.
Purpose of the Study:
- To investigate the clinical significance and molecular mechanisms of miR-142 in human cervical cancer.
- To determine if miR-142 functions as a tumor suppressor in cervical cancer.
Main Methods:
- Quantitative real-time PCR to assess miR-142 expression in cervical cancer tissues and cell lines.
- Correlation analysis between miR-142 expression and clinical parameters (FIGO stage, lymphatic metastasis).
- Functional assays (proliferation, invasion, apoptosis) in SiHa and HeLa cells with miR-142 overexpression.
- Luciferase reporter assays and Western blotting to identify and validate HMGB1 as a direct target of miR-142.
Main Results:
- miR-142 expression was significantly downregulated in cervical cancer tissues and cell lines.
- Lower miR-142 levels correlated with advanced FIGO stage and lymphatic metastasis.
- Overexpression of miR-142 suppressed cell proliferation and invasion, while enhancing apoptosis in cervical cancer cells.
- High-mobility group box 1 protein (HMGB1) was identified as a direct target of miR-142, with inverse expression correlation.
- Ectopic HMGB1 expression counteracted the tumor-suppressive effects of miR-142.
Conclusions:
- miR-142 acts as a tumor suppressor in cervical cancer by inhibiting cell proliferation and invasion and promoting apoptosis.
- These effects are mediated through the direct targeting of HMGB1.
- miR-142-HMGB1 axis represents a potential therapeutic strategy for cervical cancer.
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