miR-100-5p and miR-203a-3p suppress esophageal squamous cell carcinoma progression by targeting FKBP5

TL;DR

This study shows that miR-100-5p and miR-203a-3p reduce the spread of esophageal cancer by targeting FKBP5, a protein linked to worse outcomes.

Contribution

Identifies miR-100-5p and miR-203a-3p as tumor suppressors targeting FKBP5 in poorly differentiated esophageal cancer.

Findings

miR-100-5p and miR-203a-3p are downregulated in poorly differentiated ESCC and linked to worse survival.

Overexpression of these miRNAs reduces cancer cell migration and invasion.

FKBP5 is a common target, and its high expression correlates with poor patient outcomes.

Abstract

Poorly differentiated cancers, including esophageal squamous cell carcinoma (ESCC), exhibit higher malignant potential and worse prognoses than well-differentiated types. The present study aimed to identify microRNAs (miRNAs or miRs) involved in ESCC progression and their target mRNAs, focusing on tumor differentiation. miRNA candidates were selected using a miRNA array-based approach and GEO datasets, comparing expression levels between poorly and non-poorly differentiated ESCC. Clinical samples (n=61) and cell lines were analyzed to determine the significance and function of the selected miRNAs and their target mRNA. miR-100-5p and miR-203a-3p were significantly downregulated in poorly differentiated ESCC, with lower expression strongly associated with poorer overall survival (OS) (miR-100-5p: P=0.02; miR-203a-3p: P=0.05) and relapse-free survival (RFS) (miR-100-5p: P=0.04; miR-203a-3p: P=0.12). Overexpression of these miRNAs suppressed cell migration and invasion. FKBP5 was identified as a common target, with its expression significantly reduced upon double-transfection with miR-100-5p and miR-203a-3p. FKBP5 downregulation reduced tumor aggressiveness in KYSE70 cells, and clinical samples showed significantly worse survival rates in patients with high FKBP5 expression (OS: P=0.02; RFS: P=0.04). These findings suggest that miR-100-5p and miR-203a-3p act as tumor suppressors by targeting FKBP5, highlighting FKBP5 as a potential therapeutic target in ESCC.

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