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

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. <i>FKBP5</i> was identified as a common target, with its expression significantly reduced upon double‑transfection with miR‑100‑5p and miR‑203a‑3p. <i>FKBP5</i> downregulation reduced tumor aggressiveness in KYSE70 cells, and clinical samples showed significantly worse survival rates in patients with high <i>FKBP5</i> 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 <i>FKBP5</i>, highlighting <i>FKBP5</i> as a potential therapeutic target in ESCC.