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MiR-127-3p inhibits proliferation of ovarian cancer in rats through down-regulating MAPK4
1Department of Obstetrics and Gynecology, Jinan City People's Hospital, Jinan, China. 851256@qq.com.
Objective:
To reveal the anti-tumor effect of micro ribonucleic acid (miR)-127-3p on epithelial ovarian cancer (EOC).
Patients And Methods:
The expression of miR-127-3p in 7 kinds of EOC cell lines and 10 cases of clinical samples of EOC patients was detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). OVCAR-3 and Caov-3 cell lines were transfected with lentiviruses to overexpress endogenous miR-127-3p. Then, the anti-tumor effect of miR-127-3p on EOC cells was explored through the in vitro cell proliferation assay, bufalin sensitivity assay, wound healing assay, and invasion assay. In addition, whether the mitogen-activated protein kinase 4 (MAPK4) gene is a downstream target of miR-127-3p in EOC was verified via Dual-Luciferase reporter assay and qRT-PCR. The involvement of MAPK4 in regulating phenotypes of OVCAR-3 and Caov-3 cells was finally explored.
Results:
MiR-127-3p was downregulated in both EOC cell lines and EOC tissues (p<0.05). After lentivirus-mediated overexpression of miR-127-3p, in vitro proliferation and invasion of EOC cells were inhibited, and the sensitivity to bufalin was enhanced (p<0.05). MiR-127-3p directly regulated MAPK4 gene in EOC. Moreover, the upregulation of MAPK4 inhibited the anti-tumor effect of miR-127-3p on EOC, manifested as the remarkably enhanced cell proliferation and migration (p<0.05), and the weakened sensitivity to bufalin (p<0.01).
Conclusions:
MiR-127-3p exerts an inhibitory effect on EOC cells via regulating MAPK4 level.
Insights
Micro ribonucleic acid (miR)-127-3p inhibits epithelial ovarian cancer (EOC) by downregulating MAPK4. This discovery offers new therapeutic targets for EOC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Epithelial ovarian cancer (EOC) remains a leading cause of cancer-related mortality in women.
- Identifying novel molecular targets for EOC therapy is crucial for improving patient outcomes.
- MicroRNAs (miRNAs) have emerged as critical regulators of cancer development and progression.
Purpose of the Study:
- To investigate the anti-tumor role of micro ribonucleic acid (miR)-127-3p in epithelial ovarian cancer (EOC).
- To elucidate the molecular mechanism underlying the action of miR-127-3p in EOC.
- To explore the potential of miR-127-3p as a therapeutic agent for EOC.
Main Methods:
- Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) to detect miR-127-3p expression in EOC cell lines and tissues.
- Lentiviral transfection to overexpress miR-127-3p in EOC cells (OVCAR-3 and Caov-3).
- In vitro assays including proliferation, bufalin sensitivity, wound healing, and invasion assays to assess anti-tumor effects.
- Dual-Luciferase reporter assay and qRT-PCR to validate MAPK4 as a direct target of miR-127-3p.
- Functional studies to explore the role of MAPK4 in EOC cell phenotypes.
Main Results:
- MiR-127-3p was significantly downregulated in EOC cell lines and clinical samples.
- Overexpression of miR-127-3p inhibited EOC cell proliferation and invasion, and enhanced sensitivity to bufalin.
- MiR-127-3p directly targets and regulates the expression of the mitogen-activated protein kinase 4 (MAPK4) gene in EOC.
- Upregulation of MAPK4 counteracted the anti-tumor effects of miR-127-3p, promoting proliferation and migration while reducing bufalin sensitivity.
Conclusions:
- MiR-127-3p functions as a tumor suppressor in EOC.
- The anti-tumor activity of miR-127-3p is mediated through the direct regulation of MAPK4 expression.
- Targeting the miR-127-3p/MAPK4 axis presents a promising therapeutic strategy for epithelial ovarian cancer.
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