Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of Prostate Cancer via Targeting miR-198 and Promoting the MAPK1 Pathway

Abstract

Prostate cancer has become the most commonly diagnosed and the second leading cause of cancer-related deaths in males. The long noncoding RNA second chromosome locus associated with prostate-1 (SChLAP1) has been found to be overexpressed in a subset of prostate cancer. However, the significance and mechanism of SChLAP1 in prostate cancer are not well known. In this study, we explored the role of SChLAP1 in prostate cancer tissues, cell lines, and mouse models. The effect of SChLAP1 on miR-198 and MAPK1 was specifically examined. We found that SChLAP1 expression was significantly increased in prostate cancer cells and tissues. Knockdown of SChLAP1 promoted apoptosis and inhibited cell proliferation and invasion in vitro and in vivo. In addition, a potential bonding site between miR-198 and SChLAP1 was predicted, and a low expression of miR-198 was found in prostate cancer tissues and cells. Knockdown of SChLAP1 significantly increased the expression of miR-198, and SChLAP1 overexpression markedly decreased it, indicating that SChLAP1 acted as a negative regulator in the expression of miR-198. Furthermore, our results showed that SChLAP1 interacted with miR-198 and subsequently modulated the MAPK1 signaling pathway in prostate cancer. In conclusion, our study has identified a novel pathway through which SChLAP1 exerts its oncogenic role in prostate cancer at the level of miRNAs and provided a molecular basis for potential applications of SChLAP1 in the prognosis and treatment of prostate cancer.

Development of an autophagy-related gene expression signature for prognosis prediction in prostate cancer patients

“…Previous research has shown that ULK2 and ATG4D were hub autophagy genes, which are necessary for maximal androgen-mediated autophagy and cell proliferation and also associated with poor prognosis in PCa [14]. Li et al demonstrated that MAPK1 plays an important role in regulating cancer cell invasion and metastasis in vitro and in vivo [20]. Forkhead box transcription factor-1 (FOXO1) is a tumor suppressor that is downregulated in human prostate cancer, which acts as a repression target of EZH2 and an essential mediator of EZH2 inhibition-induced cell death [21].…”

A novel long noncoding RNA LINC00844 regulates prostate cancer cell migration and invasion through androgen receptor signaling

“…4c, we did not observe any significant increase in cell proliferation after LINC00844 depletion. While many reported lncRNAs in prostate cancer are known to affect cell proliferation and migration [26,31], our results show LINC00844 affects exclusively prostate cancer cell migration and invasion, without affecting cell proliferation. Collectively, these results suggest that LINC00844 (i) is critical for preventing a metastatic phenotype in prostate cancer cells and (ii) mediates its effects through the AR signaling pathway.…”

MicroRNA181c inhibits prostate cancer cell growth and invasion by targeting multiple ERK signaling pathway components

“…For example, it has been reported that miR543, miR217, and miR20b served as tumor suppresser miRNAs by targeting ERK2 in cancers of breast, colon/rectum, or thyroid. The microRNAs miR198, miR329‐3p, and miR634 also target ERK2, suppressing tumor cell proliferation, migration, and invasion, or restoring drug sensitivity in prostate, uterine cervical, and ovarian cancers. RSK2 is a target of miR375 and miR634 .…”