miR-193b-3p suppresses lung cancer cell migration and invasion through PRNP targeting

作者：Hsiang‐Ling Ho, Shin-Chih Lin, Chao‐Wei Chiang, Ching‐Yu Lin, Che-Wei Liu, Yi‐Chen Yeh, Mei‐Yu Chen, Teh-Ying Chou · 发表于：Journal of Biomedical Science · 年份：2025 · DOI：10.1186/s12929-025-01121-1 · 被引用次数：12 · 研究领域：Prion Diseases and Protein Misfolding、Hedgehog Signaling Pathway Studies、RNA Research and Splicing

BACKGROUND: Tumor metastasis is responsible for approximately 90% of mortality in lung cancer. Understanding the molecular mechanisms of lung cancer metastasis is crucial for developing new treatment strategies. Cellular prion protein (PrPc), encoded by PRNP gene, was previously found to enhance lung cancer invasiveness. However, research on the post-transcriptional regulation of PRNP remains limited. METHODS: Dual-luciferase reporter assays identified miRNAs targeting the PRNP 3'-UTR, and RNA immunoprecipitation (RIP) confirmed the interaction between miR-193b-3p and PRNP mRNA. Promoter deletions and chromatin immunoprecipitation (ChIP) assays established c-Jun as a transcriptional repressor of miR-193b-3p. Functional validation of the c-Jun-miR-193b-3p-PrPc axis was conducted using transwell assays, LNA-in situ hybridization, RT-PCR, Western blot, and immunohistochemistry. Subcutaneous mouse xenograft models assessed the anti-tumor effects of miR-193b-3p in vivo. RESULTS: We demonstrated that miR-193b-3p downregulates PrPc expression by directly targeting the 3'-UTR of PRNP. Overexpression of miR-193b-3p significantly suppressed PRNP expression at both mRNA and protein levels, and reduced lung cancer cell migration, invasion and proliferation, which was reversed by PrPc overexpression. Conversely, miR-193b-3p silencing enhanced PRNP expression as well as those oncogenic properties, which were mitigated by PRNP knockdown. Spearman correlation analysis revealed a significant ...