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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
MicroRNA-492 overexpression involves in cell proliferation, migration, and radiotherapy response of cervical squamous
Mei Liu1, Jusheng An2, Manni Huang2
1Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P. R. China.
Abstract:
MicroRNAs (miRNAs) are small non-coding RNA that target protein-coding mRNAs at the post-transcriptional level. The aim of this study was to define the role of miR-492 in cervical squamous cell carcinomas. After microRNA profiling and comparison, we firstly detected miR-492 expression in 104 tumor tissues biopsies derived from advanced staged (FIGO IIB-IIIB) cervical squamous cell carcinoma patients before receiving concomitant chemoradiotherapy and found miR-492 expression was significantly higher in the specimens that were sensitive to concomitant chemoradiotherapy, as compared with insensitive cancer specimens (P < 0.05). Moreover, higher expression of miR-492 was associated with pelvic lymph node metastasis (LNM) (P < 0.05). Further studies illustrated ectopic miR-492 overexpression in SiHa cells promoted cell proliferation, migration, and enhanced the sensitivity of cervical cancer cells to irradiation by promoting apoptosis. In addition, we identified TIMP2 as a direct miR-492 target, which has been shown to be critical in modulating cancer cell migration and invasion. We also confirmed that miR-492 expression levels in positive pelvic LNM were much higher than negative LNM and miR-492 played a vital role in pelvic lymph node metastasis via regulating miR-492/TIMP2/MMP10 axis. In particular, miR-492 was correlated with prognosis in the subgroup of patients with negative pelvic LNM (P < 0.05) and had a promising value in predicting treatment response in the subgroup of patients with positive pelvic LNM (an AUC of 85%, 75.00% specificity, and 95.24% sensitivity). Taken together, the results suggested that miR-492 may serve as a potential biomarker for cervical cancer treatment and prognosis.
Insights
MicroRNA 492 (miR-492) is upregulated in cervical cancer, correlating with treatment sensitivity and lymph node metastasis. It enhances cell proliferation and radiation sensitivity, potentially serving as a biomarker for cervical cancer prognosis and treatment response.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- MicroRNAs (miRNAs) are key post-transcriptional regulators.
- Cervical squamous cell carcinoma (CSCC) presents treatment challenges.
- Understanding miRNA roles is crucial for targeted therapies.
Purpose of the Study:
- To investigate the role of miR-492 in CSCC.
- To assess miR-492 expression in relation to treatment response and metastasis.
- To explore the functional impact of miR-492 in cervical cancer cells.
Main Methods:
- MicroRNA profiling of 104 advanced CSCC patient biopsies.
- Analysis of miR-492 expression in relation to chemoradiotherapy sensitivity and lymph node metastasis (LNM).
- In vitro studies involving ectopic miR-492 overexpression in SiHa cells; target validation (TIMP2).
Main Results:
- miR-492 was significantly higher in chemoradiotherapy-sensitive tumors and associated with pelvic LNM.
- Overexpression of miR-492 promoted cell proliferation, migration, and enhanced radiosensitivity.
- miR-492 directly targets TIMP2, regulating the miR-492/TIMP2/MMP10 axis in pelvic LNM.
- miR-492 showed correlation with prognosis in negative LNM and predictive value for treatment response in positive LNM.
Conclusions:
- miR-492 is upregulated in CSCC and linked to treatment response and metastasis.
- miR-492 influences cervical cancer cell behavior and radiosensitivity.
- miR-492 serves as a potential biomarker for predicting treatment outcomes and prognosis in CSCC.
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