LncRNA HNF1A-AS1 promotes prostate cancer progression via the miR-138-5p/KDM6B axis

Abstract

Prostate cancer (PCa) is a widespread malignancy with poor prognosis in advanced stages. However, the role of long non-coding RNA (lncRNA) HNF1A-AS1 in PCa progression and its underlying mechanisms remain largely unclear. This study aims to explore the expression trends and clinical associations of HNF1A-AS1 in PCa, and to reveal the potential functional networks by which it regulates the malignant progression of PCa. Expression of HNF1A-AS1 was detected in 113 pairs of PCa and adjacent tissues by quantitative real-time PCR (qRT-PCR). Cell Counting Kit-8 (CCK-8), Transwell, Western blot, and Fe²⁺ concentration assays were performed to assess cell proliferation, migration, invasion, and ferroptosis. Dual-luciferase reporter assays validated targeting relationships. HNF1A-AS1 was markedly upregulated in PCa tissues and cells. High expression of HNF1A-AS1 correlated with advanced tumor progression, poor differentiation, higher Gleason grade, and reduced recurrence-free survival. Silencing of HNF1A-AS1 suppressed PCa cell proliferation, migration, and invasion, and triggered biochemical events consistent with ferroptosis. Mechanistically, HNF1A-AS1 directly sponged miR-138-5p, which in turn targeted KDM6B. Rescue experiments confirmed that the HNF1A-AS1/miR-138-5p/KDM6B axis regulates malignant phenotypes and ferroptosis in PCa cells. HNF1A-AS1 represents a potential independent prognostic factor for PCa. HNF1A-AS1 drives PCa progression through suppression of ferroptosis via the miR-138-5p/KDM6B axis, representing a promising therapeutic candidate.