Mir-142-5p Suppresses Ovarian Cancer Metastasis by Inhibiting the Epithelial-Mesenchymal Transition via DNMT1

Aim/Background

Ovarian Cancer (OC) accounts for the highest number of deaths among gynecological cancers. Our research is focused on investigating the therapeutic potential and the fundamental mechanism by which miR-142-5p exerts its effects in the treatment of OC.

Materials and Methods

The GSE53829 and GSE83693 data sets were collected for targeted miRNA identification. RT-qPCR was conducted to evaluate the expression levels of miRNA, N-cadherin, ZO-1, Claudin-1, E-cadherin, and DNMT1 mRNA expressions. Additionally, the protein expressions of these mentioned molecules were quantified using western blot analysis. The invasion and migratory abilities of OC cells were assessed through transwell and wound healing assays. Additionally, the possible interaction between miR-142-5p and DNMT1 was identified and confirmed using the Targetscan database in conjunction with a luciferase assay.

Results

The mRNA levels of miR-142-5p showed a notable reduction in both OC cell lines and metastatic tumors, as compared to their counterparts of normal ovarian cancer cells and non-metastatic tumors, respectively. Besides, the inhibition or overexpression of miR-142-5p had a significant impact on the migration, invasion ability, and Epithelial-Mesenchymal Transition (EMT) process of OC cells. The levels of DNMT1 were significantly increased in metastatic tumors and were notably affected by the expression of miR-142-5p. Moreover, interaction between DNMT1 mRNA and miR-142-5p was confirmed, and the knockdown of DNMT1 effectively counteracted the significant reversal in OC cell migration, invasion, and EMT caused by miR-142-5p suppression.

Conclusion

The role of miR-142-5p on OC metastasis is attributed to its ability to suppress EMT through DNMT1, indicating the promising therapeutic potential of miR-142-5p in the treatment of OC.