Hypoxia induced microRNA-301b-3p overexpression promotes proliferation, migration and invasion of prostate cancer cells by targeting LRP1B

Abstract

Prostate cancer is a high burden on society worldwide due to its high morbidity and mortality. Growing evidence has implicated microRNAs (miRNAs or miRs) in the occurrence and progression of prostate cancer. The present study was conducted with main emphasis put on the possible effect of hypoxia-induced miR-301b-3p on prostate cancer by targeting low-density lipoprotein receptor-related protein 1B (LRP1B). Firstly, the differentially expressed genes were identified by conducting microarray-based gene expression profiling of prostate cancer. Next, the expression of miR-301b-3p in prostate cancer cells was examined in cells treated with 1% oxygen or dimethyloxalylglycine (DMOG), and the cell line with the highest miR-301b-3p expression was selected for subsequent experiments. Subsequently, the target relationship between miR-301b-3p and LRP1B was identified. The effect of miR-301b-3p and LRP1B on cell proliferation, migration and invasion as well as tumorigenicity of transfected cells was examined using the gain- and loss-of-function approaches. Hypoxia induced miR-301b-3p was highly expressed while LRP1B was poorly expressed in prostate cancer. Moreover, miR-301b-3p could down-regulate LRP1B by interacting with LRP1B, which acted to promote the proliferation, migration and invasion abilities of prostate cancer cells in addition to tumor growth in vivo. In addition, up-regulation of LRP1B can reverse the promoting effect of miR-301b-3p on the aforementioned factors. Collectively, up-regulation of miR-301b-3p induced by hypoxia could potentially accelerate proliferation, migration and invasion of prostate cancer cells via the inhibitory effect on LRP1B expression, highlighting that miR-301b-3p may be instrumental for the therapeutic targeting of prostate cancer.