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MiR-125a regulates ovarian cancer proliferation and invasion by repressing GALNT14 expression
Juan Yang1, Guiyuan Li2, Keqiang Zhang1
1Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central south University, Changsha 410078, Hunan, PR China.
Abstract:
Increasing evidence has suggested that dysregulation of microRNAs (miRNAs) could contribute to tumor progression. The miR-125a was downregulated in several types of cancer, however, the molecular mechanism of miR-125a in the ovarian cancer remains unclear. The aim of the paper was to reveal the mechanism of miR-125a regulating cell proliferation and metastasis in ovarian cancer. In this study, western blotting, immunohistochemistry and serum-ELISA assay revealed that polypeptide N-acetylgalactosaminyl transferase 14 (GALNT14) expression was upregulated and correlated with the cancer stage in ovarian cancer. The expression levels of miR-125a were downregulated and negatively related to GALNT14 expression in clinical ovarian cancer tissues. Moreover, luciferase reporter assay identified polypeptide N-acetylgalactosaminyl transferase 14 (GALNT14) as a direct target of miR-125a, and overexpression of miR-125a markedly reduced the expression of GALNT14 in ovarian cancer. Functional characterization of miR-125a was accomplished by reconstitution of miR-125a and silencing GALNT14 expression in ovarian cancer cells to determine changes in proliferation and invasion. The MTT assay and transwell assay revealed that miR-125a transfectant significantly inhibits cell proliferation and invasion, by repressing GALNT14 expression. Furthermore, the gelatin zymography assay miR-125a mimics and GALNT14 siRNA suppressed the activity of MMP2 and MMP9. Taken together, our findings show that miR-125a functions as tumor suppressor in ovarian cancer by targeting GALNT14, and miR-125a may therefore serve as a biomarker for diagnosis and therapeutics in ovarian cancer.
Insights
MicroRNA-125a (miR-125a) acts as a tumor suppressor in ovarian cancer by targeting GALNT14. Restoring miR-125a inhibits cancer cell proliferation and metastasis, suggesting its potential as a diagnostic and therapeutic biomarker.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- MicroRNAs (miRNAs) play a role in cancer progression.
- miR-125a is downregulated in various cancers, but its mechanism in ovarian cancer is unclear.
- Ovarian cancer progression involves complex molecular dysregulations.
Purpose of the Study:
- To elucidate the mechanism of miR-125a in regulating ovarian cancer cell proliferation and metastasis.
- To identify the molecular targets of miR-125a in ovarian cancer.
- To evaluate the potential of miR-125a as a biomarker for ovarian cancer.
Main Methods:
- Western blotting, immunohistochemistry, and ELISA to assess GALNT14 expression.
- Luciferase reporter assay to confirm direct targeting of GALNT14 by miR-125a.
- MTT, Transwell, and gelatin zymography assays to evaluate functional effects of miR-125a and GALNT14 on cell proliferation, invasion, and MMP activity.
Main Results:
- GALNT14 expression is upregulated and correlates with ovarian cancer stage.
- miR-125a is downregulated and inversely related to GALNT14 expression in ovarian cancer tissues.
- Overexpression of miR-125a suppresses ovarian cancer cell proliferation and invasion by repressing GALNT14.
- miR-125a and GALNT14 modulation affects MMP2 and MMP9 activity.
Conclusions:
- miR-125a functions as a tumor suppressor in ovarian cancer by targeting GALNT14.
- miR-125a inhibits ovarian cancer cell proliferation and metastasis.
- miR-125a holds potential as a diagnostic and therapeutic biomarker for ovarian cancer.
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