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MiR-143 targets CTGF and exerts tumor-suppressing functions in epithelial ovarian cancer
Lufei Wang1, Jin He2, Hongmei Xu2
1Department of Ophthalmology, The Second Hospital of Jilin University Changchun 130041, Jilin Province, P.R. China.
Abstract:
A series of recent studies suggested that miR-143 might involve in the tumorigenesis and metastasis of various cancer types. However, the biological function and underlying mechanisms of miR-143 in human epithelial ovarian carcinoma (EOC) remain unknown. Therefore, this study aimed to investigate the miR-143 expression and its clinical diagnosis significance in patients suffering EOC and to analyze its role and underlying molecular mechanism in EOC. Our result showed that the expression levels of miR-143 were downregulated in EOC tissues and cell lines, was associated with International Federation of Gynaecology and Obstetrics (FIGO) stage, pathological grade and lymph node metastasis (all P < 0.01) . Overexpression of miR-143 significantly inhibited EOC cell proliferation, migration, and invasion. Furthermore, computational algorithm combined with luciferase reporter assays identified connective tissue growth factor (CTGF) as the direct target of miR-143 in EOC cells. The expression level of CTGF was significantly increased in EOC tissues, was inversely correlated with miR-143 expression in clinical EOC tissues. Knockdown of CTGF mimicked the suppression effect induced by miR-143 overexpression. Restoration of CTGF expression partially reversed the suppression effect induced by miR-143 overexpression. These results suggested that miR-143 inhibited EOC cell proliferation, migration, and invasion, at least in part, via suppressing CTGF expression.
Insights
MicroRNA-143 (miR-143) is downregulated in epithelial ovarian carcinoma (EOC), inhibiting tumor growth and metastasis by targeting connective tissue growth factor (CTGF). This suggests miR-143 as a potential biomarker and therapeutic target for EOC.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- MicroRNA-143 (miR-143) has been implicated in various cancers, but its role in epithelial ovarian carcinoma (EOC) is unclear.
- Understanding miR-143's function and mechanisms in EOC is crucial for developing new diagnostic and therapeutic strategies.
Purpose of the Study:
- To investigate miR-143 expression and its clinical significance in EOC.
- To elucidate the biological role and molecular mechanisms of miR-143 in EOC progression.
Main Methods:
- Quantitative real-time PCR to assess miR-143 expression in EOC tissues and cell lines.
- Cell proliferation, migration, and invasion assays to evaluate miR-143's functional role.
- Bioinformatic analysis and luciferase reporter assays to identify miR-143 targets.
- Western blotting and rescue experiments to validate the miR-143/CTGF interaction.
Main Results:
- miR-143 expression was significantly downregulated in EOC tissues and cell lines.
- Low miR-143 levels correlated with advanced FIGO stage, poor pathological grade, and lymph node metastasis.
- Overexpression of miR-143 suppressed EOC cell proliferation, migration, and invasion.
- Connective tissue growth factor (CTGF) was identified as a direct target of miR-143.
- CTGF expression was upregulated in EOC and inversely correlated with miR-143 levels.
- CTGF knockdown mimicked miR-143's suppressive effects, while CTGF restoration partially reversed them.
Conclusions:
- miR-143 acts as a tumor suppressor in EOC by inhibiting proliferation, migration, and invasion.
- The tumor-suppressive function of miR-143 is mediated, at least partly, through the downregulation of CTGF.
- miR-143 may serve as a potential diagnostic biomarker and therapeutic target for EOC.
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