LINC00992 exerts oncogenic activities in prostate cancer via regulation of SOX4

The critical role of long non-coding RNAs (lncRNAs) has been implicated in prostate cancer (PCa). As one of them, LINC00992 (LNC992) has been revealed by bioinformatics prediction to be significantly overexpressed in PCa. However, the underlying mechanism of LNC992 in PCa has not been well investigated. First, gene expression microarrays of prostate adenocarcinoma (PRAD) were downloaded from the GEO database, and differentially expressed genes were analyzed. Subsequently, we assessed the LNC992 expression in PCa patients. PCa cells with overexpression or low expression of LNC992 were generated, followed by the examination of proliferation, invasion and migration in vitro and in vivo. The differentially expressed genes were analyzed by microarrays after altering LNC992 expression in PCa cells, and the downstream regulatory mechanisms of LNC992 were analyzed by bioinformatics analysis and validated by RIP and RNA pull-down assays. LNC992 was highly expressed in the PRAD database and in cancer tissues from PCa patients, serving as a poor prognostic factor for PCa patients. Knockdown of LNC992 significantly inhibited PCa cell growth, metastasis, and angiogenesis in vitro and in vivo. Moreover, we found that knockdown of LNC992 significantly suppressed SOX4 expression in cells and that LNC992 could bind to EIF4A3 and promote the translation of SOX4. Inhibition of either EIF4A3 or SOX4 significantly suppressed the growth and metastasis of PCa cells. LNC992 elevates SOX4 expression by binding to SOX4 mRNA and recruiting translation initiation factor EIF4A3, thereby promoting the growth and metastasis of PCa cells in vitro and in vivo.