SChLAP1 regulates the metastasis and apoptosis of prostate cancer partly via miR-101.

Abstract

Background: Prostate cancer (PC) remains one of the leading causes of cancer-related mortality, necessitating further research into novel prognostic biomarkers and therapeutic targets. Long noncoding RNA second chromosome locus-associated with prostate-1 (SChLAP1) plays a crucial role in the aggressiveness of PC; however, its precise mechanism remains unclear. This study aimed to investigate the role of SChLAP1 in PC metastasis and apoptosis, with a particular focus on its interaction with miR-101.

Methods: The expression levels of SChLAP1 were analyzed by quantitative polymerase chain reaction (qPCR) and fluorescence in situ hybridization (FISH) in 42 clinical specimens, including 21 PC tissues and their corresponding adjacent normal tissues, as well as in PC cell lines (PC-3, DU145, and LNCaP). Functional assays were performed using lentivirus-mediated knockdown and overexpression of SChLAP1 and miR-101-5p. Cell proliferation, invasion, apoptosis, and autophagy were assessed via Cell Counting Kit-8 assays, Transwell migration assays, flow cytometry, and Western blot analysis. Bioinformatics analysis and complementary expression experiments were used to validate the interaction between SChLAP1 and miR-101-5p. An in vivo xenograft model was established by subcutaneously implanting PC-3 cells into nude mice to evaluate tumor growth.

Results: SChLAP1 was significantly upregulated in PC tissues and was correlated with higher Gleason scores (P<0.05). Knockdown of SChLAP1 suppressed PC-3 cell proliferation, invasion, and cell cycle progression while promoting apoptosis through MMP-9/Bcl-2 downregulation and caspase-3 activation. SChLAP1 functioned as a cytoplasmic competing endogenous RNA (ceRNA) by directly binding to miR-101-5p. Overexpression of miR-101-5p inhibited metastasis and induced apoptosis but had no significant effect on autophagy. In vivo, both SChLAP1 knockdown and miR-101-5p overexpression significantly reduced tumor volume.

Conclusions: SChLAP1 promotes PC progression by regulating metastasis and apoptosis via the miR-101-5p axis. The SChLAP1/miR-101-5p signaling pathway represents a novel diagnostic and therapeutic target, with potential implications for improving prognostic assessment and treatment strategies for advanced PC. Further clinical studies are warranted to evaluate its therapeutic potential in clinical settings.