Combined targeting of TCF7L1/2, PTEN, CDK6, and BCCIP by microRNA miR‐29c‐3p is associated with reduced invasion and proliferation of endometriotic cells

TL;DR

This study shows that the microRNA miR-29c-3p reduces the growth and spread of endometriotic cells by targeting several key genes.

Contribution

The paper identifies multiple molecular targets of miR-29c-3p involved in endometriosis progression.

Findings

miR-29c-3p reduced cell viability and S-phase progression in endometriotic cells.

miR-29c-3p inhibited 12Z cell invasion and altered expression of CDK6, PTEN, TCF7L1/2, and BCCIP.

Dysregulation of these targets was confirmed in endometriotic lesions using the EndometDB database.

Abstract

Endometriosis is a chronic gynecological disorder associated with pain symptoms and infertility. The expression of microRNA miR‐29c‐3p is dysregulated in endometriosis. We aimed to identify novel molecular targets of miR‐29c‐3p functionally linked to proliferation and invasive growth in endometriosis.

The epithelial endometriotic cell line 12Z and primary endometriotic stromal cells (PESC) were transfected with control miRNA or pre‐miR‐29c‐3p, and subjected to cell cycle analysis, cell viability, wound healing, and Matrigel invasion assays. Expression of bioinformatically predicted miR‐29c‐3p targets was analyzed by qPCR and western blot. Target gene expression in endometriotic lesions and healthy endometrium was studied in the EndometDB endometriosis database.

miR‐29c‐3p decreased 12Z and PESC cell viability and the proportion of PESC in the S‐phase. 12Z cell invasion, but not migration, was decreased after miR‐29c‐3p upregulation. miR‐29c‐3p decreased the mRNA expression of CDK6, BCCIP, TCF7L1, TCF7L2, PTEN, COL4A1, E‐Cadherin, and N‐Cadherin. A decrease of CDK6 and PTEN and an increase of p21 were confirmed at the protein level. EndometDB database analysis demonstrated dysregulated expression of the selected targets in both deep endometriosis and ovarian endometriosis.

miR‐29c‐3p effectively curbs endometriotic cell proliferation and invasion by combined inhibition of cell cycle regulators and transcription factors, unveiling a promising therapeutic strategy.

miR‐29c, a microRNA dysregulated in endometriosis, is targeting several cell cycle and transcriptional regulators, which are significantly dysregulated in endometriosis. In a cell culture model, miR‐29c induced changes in cell viability, cell cycle progression and invasive growth, which are cellular properties regulated by the newly identified molecular targets.

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