Ma Huanxin, Wang Huihan, Tian Fei, Zhong Yuan, Liu Zhuogang, Liao Aijun
Department of Hematology, Shengjing Hospital of China Medical University, Shenyang, China.
Front Oncol. 2020 Apr 15;10:438. doi: 10.3389/fonc.2020.00438. eCollection 2020.
PIWI-interacting RNA (piRNA) is a kind of non-coding single stranded RNA which plays major roles in epigenetic expressions, genome rearrangement, and regulation of gene and protein. Because piRNAs are abnormally expressed in various cancers, they can be used as novel biomarkers and therapeutic targets. However, the roles of piRNAs in cancer cell growth and survival are not well-known. Here, we are the first to provide evidence that PIWI-interacting RNA-004800 (piR-004800) is overexpressed in both exosomes from multiple myeloma (MM) patients' bone marrow supernatant and primary MM cells. The expression level of piR-004800 is positively correlated with the stages of MM, according to the international staging system (ISS). In MM cell lines, downregulation of piR-004800 induced apoptosis and autophagic cell death. This was accompanied by and inhibition of cell proliferation. Our previous study shows that sphingosine-1-phosphate receptor (S1PR) signaling pathway plays a crucial part in MM cell proliferation. In this study, we find that S1PR signaling pathway can regulate the PI3K/Akt/mTOR pathway through control of piR-004800 expressions. Taken together our data supports an oncogenic role for piR-004800 in MM, which sheds insight into a new mechanism that may lead to therapeutic targets in MM, an incurable plasma cell neoplasm.
PIWI相互作用RNA（piRNA）是一种非编码单链RNA，在表观遗传表达、基因组重排以及基因和蛋白质调控中发挥着重要作用。由于piRNA在各种癌症中异常表达，它们可作为新型生物标志物和治疗靶点。然而，piRNA在癌细胞生长和存活中的作用尚不清楚。在此，我们首次提供证据表明，PIWI相互作用RNA - 004800（piR - 004800）在多发性骨髓瘤（MM）患者骨髓上清液的外泌体和原发性MM细胞中均过表达。根据国际分期系统（ISS），piR - 004800的表达水平与MM的分期呈正相关。在MM细胞系中，piR - 004800的下调诱导细胞凋亡和自噬性细胞死亡。这伴随着细胞增殖的抑制。我们之前的研究表明，鞘氨醇-1-磷酸受体（S1PR）信号通路在MM细胞增殖中起关键作用。在本研究中，我们发现S1PR信号通路可通过控制piR - 004800的表达来调节PI3K/Akt/mTOR通路。综合我们的数据支持piR - 004800在MM中具有致癌作用，这为一种可能导致MM（一种无法治愈的浆细胞肿瘤）治疗靶点的新机制提供了见解。
