FHL1 Inhibition by Mir-1301-3p Promotes Uterine Corpus Endometrial Carcinoma Cell Proliferation and Migration: A Prognostic Insight.

Abstract

Background: The impact of microRNA-1301-3p (miR-1301-3p) on various cancer subtypes is noteworthy. However, its specific role within the framework of uterine corpus endometrial carcinoma (UCEC) is yet to be clearly defined.

Objective: The objective of this research was to investigate and clarify the function of miR-1301-3p in relation to UCEC.

Methods: Sample data for our study were sourced from The Cancer Genome Atlas (TCGA). Using various statistical techniques, we assessed the potential of miR-1301-3p as a diagnostic and prognostic indicator, as well as its association with clinical characteristics. Additionally, we conducted an analysis of the genes targeted by miR-1301-3p. The expression levels of miR-1301-3p in uterine corpus endometrial carcinoma (UCEC) cell lines were determined by quantitative real-time PCR (qRT-PCR). Cellular viability and migratory capacity were measured using the CCK8 assay and Transwell migration assays, respectively. Moreover, the expression levels of genes and proteins targeted by miR-1301-3p were identified through dual-luciferase reporter gene assays and Western blot analysis.

Results: Expression patterns of miR-1301-3p varied across cancer subtypes, which were significantly linked to specific histological classifications, achieving statistical significance (p < 0.001). In UCEC, higher miR-1301-3p levels correlated with reduced overall survival (p = 0.012) and progression-free survival (p = 0.016), and it emerged as an independent prognostic marker for UCEC. A comparative analysis revealed significantly higher miR-1301-3p levels in UCEC cell lines compared to normal endometrial epithelial cells. Four and a half LIM domains 1 (FHL1) exhibited a negative correlation with miR-1301-3p levels within UCEC tissue samples. miR-1301-3p was shown to promote UCEC cell proliferation and migration through its binding to the 3'-untranslated region (UTR) of the FHL1 gene, thereby repressing FHL1 expression. Additionally, augmenting FHL1 levels was observed to counteract the enhancing impact of miR-1301-3p on UCEC cells.

Conclusion: miR-1301-3p regulates the proliferation and migration of UCEC cells by interacting with the FHL1 gene. miR-1301-3p may serve as a promising prognostic biomarker in UCEC.