Wu Huijuan, Tian Xin, Zhu Chaoyang
Department of Telemedicine and Internet Medical Center, The Huaihe Hospital of Henan University, No. 115 Ximen Avenue, Kaifeng, 475000 Henan China.
Department of Urology Surgery, The Huaihe Hospital of Henan University, Kaifeng, Henan China.
Cancer Cell Int. 2020 Jul 2;20:283. doi: 10.1186/s12935-020-01363-z. eCollection 2020.
Prostate cancer (PCa) greatly threatens men's lives, with high incidence and mortality. Recently, the research of long non-coding RNAs (lncRNAs) has made breakthroughs in the development of human cancers. This study aimed to figure out the role and action mechanism of lncRNA PVT1 (PVT1) in PCa.
The expression of PVT1, microRNA-15a-5p (miR-15a-5p) and kinesin family member 23 (KIF23) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis, migration and invasion were assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2--tetrazolium bromide (MTT), flow cytometry and transwell assays, respectively. The protein levels of KIF23 and proliferation, apoptosis, and epithelial-mesenchymal transition (EMT)-related markers were quantified by western blot. The relationship between miR-15a-5p and PVT1 or KIF23 was predicted by starBase v2.0 and verified by dual-luciferase reporter assay. Xenograft assay was conducted to determine the role of PVT1 in vivo.
The expression of PVT1 and KIF23 was enhanced, while miR-15a-5p expression was reduced in PCa tissues and cells. PVT1 interference inhibited proliferation, migration and invasion but promoted apoptosis of PCa cells. MiR-15a-5p was a target of PVT1, and KIF23 was a target of miR-15a-5p. The inhibition of miR-15a-5p reversed the effects of PVT1 interference and suppressed the roles of KIF23 knockdown. KIF23 expression was regulated by PVT1 through miR-15a-5p. PVT1 interference blocked PCa progression in vivo.
PVT1 knockdown had effects on the progression of PCa by inhibiting the expression of KIF23 via enriching miR-15a-5p in vitro and in vivo, suggesting that PVT1 might be a novel biomarker for the treatment of PCa.
前列腺癌（PCa）严重威胁男性生命，其发病率和死亡率都很高。近年来，长链非编码RNA（lncRNAs）的研究在人类癌症的发展方面取得了突破。本研究旨在明确lncRNA PVT1（PVT1）在PCa中的作用及作用机制。
采用定量实时聚合酶链反应（qRT-PCR）检测PVT1、微小RNA-15a-5p（miR-15a-5p）和驱动蛋白家族成员23（KIF23）的表达。分别通过3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2-溴化四氮唑（MTT）、流式细胞术和Transwell实验评估细胞增殖、凋亡、迁移和侵袭情况。通过蛋白质印迹法定量检测KIF23的蛋白水平以及增殖、凋亡和上皮-间质转化（EMT）相关标志物。利用starBase v2.0预测miR-15a-5p与PVT1或KIF23之间的关系，并通过双荧光素酶报告基因实验进行验证。进行异种移植实验以确定PVT1在体内的作用。
在PCa组织和细胞中，PVT1和KIF23的表达增强，而miR-15a-5p的表达降低。干扰PVT1可抑制PCa细胞的增殖、迁移和侵袭，但促进其凋亡。miR-15a-5p是PVT1的靶标，KIF23是miR-15a-5p的靶标。抑制miR-15a-5p可逆转PVT1干扰的作用，并抑制KIF23敲低的作用。PVT1通过miR-15a-5p调节KIF23的表达。干扰PVT1可在体内阻断PCa的进展。
在体外和体内，敲低PVT1通过富集miR-15a-5p抑制KIF23的表达，从而对PCa的进展产生影响，提示PVT1可能是PCa治疗的一种新型生物标志物。
