Sun Feng, Wu Ke, Yao Zhixian, Mu Xingyu, Zheng Zhong, Sun Menghao, Wang Yong, Liu Zhihong, Zhu Yiyong
Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, People's Republic of China.
Onco Targets Ther. 2020 Jul 10;13:6755-6765. doi: 10.2147/OTT.S242441. eCollection 2020.
Metastatic disease caused by prostate cancer (PCa) is the principal cause of PCa-related mortality. Long non-protein-coding RNAs may possess significant cellular functions. Plasmacytoma variant translocation 1 (PVT1), a long non-coding RNA encoded by the human gene, is an oncogene, which can regulate several tumor-related genes. In PCa, the function and mechanism of PVT1 are unclear. NOP2 is being pursued as a prognostic marker for cancer aggressiveness, which promotes mouse fibroblast growth and tumor formation. Essentially, nothing is known about the specific interactions between the PVT1 and NOP2.
190 pairs of PCa tissues and adjacent normal tissues were collected and RNA sequencing was used to identify the differential lncRNAs. Real-time quantitative real-time PCR (RT-qPCR) confirmed these results and gene regulatory relationship. Lentiviral vectors were used to alter PVT1 and genes to analyze their effects on PCa progression. Transwell migration and invasion assays were performed to test the metastasis ability. Biofunction of PVT1 and NOP2 were confirmed in vitro and in vivo.
In this study, we reported that the long noncoding RNA-PVT1 was upregulated in PCa metastasis tissues and promoted migration of PCa cells in vitro and their metastasis in vivo. High levels of PVT1 significantly downregulated tumor suppressor microRNAs (miRNAs), such as miR-15b-5p, miR-27a-3p, miR-143-3p, and miR-627-5p, whose levels in metastasis tissues were low compared to those in non-metastasis tissues. In vitro and in vivo, PVT1 promotes PCa metastasis via targeting miRNAs. Furthermore, the expression level of PVT1 was positively associated with the expression of NOP2, a cancer metastasis-related protein. We demonstrated that NOP2 promoted invasion and migration of PCa. For specific mechanism, correlation analysis showed that PVT1 promoted metastasis by up-regulating NOP2.
Taken together, our results show that PVT1 acts as an inducer of PCa metastasis via targeting miRNAs, thereby promoting NOP2. This axis may have diagnostic and therapeutic potential for advanced PCa.
前列腺癌（PCa）引起的转移性疾病是PCa相关死亡的主要原因。长链非蛋白质编码RNA可能具有重要的细胞功能。浆细胞瘤变异易位1（PVT1）是一种由人类基因编码的长链非编码RNA，是一种癌基因，可调节多个肿瘤相关基因。在PCa中，PVT1的功能和机制尚不清楚。NOP2正被作为癌症侵袭性的预后标志物进行研究，它可促进小鼠成纤维细胞生长和肿瘤形成。本质上，关于PVT1和NOP2之间的具体相互作用一无所知。
收集190对PCa组织和相邻正常组织，采用RNA测序鉴定差异lncRNA。实时定量PCR（RT-qPCR）证实了这些结果及基因调控关系。使用慢病毒载体改变PVT1和相关基因，以分析它们对PCa进展的影响。进行Transwell迁移和侵袭试验以检测转移能力。在体外和体内证实了PVT1和NOP2的生物学功能。
在本研究中，我们报道长链非编码RNA-PVT1在PCa转移组织中上调，并在体外促进PCa细胞迁移及在体内促进其转移。高水平的PVT1显著下调肿瘤抑制性微小RNA（miRNA），如miR-15b-5p、miR-27a-3p、miR-143-3p和miR-627-5p，其在转移组织中的水平低于非转移组织。在体外和体内，PVT1通过靶向miRNA促进PCa转移。此外，PVT1的表达水平与癌症转移相关蛋白NOP2的表达呈正相关。我们证明NOP2促进PCa的侵袭和迁移。对于具体机制，相关性分析表明PVT1通过上调NOP2促进转移。
综上所述，我们的结果表明PVT1通过靶向miRNA作为PCa转移的诱导因子，从而促进NOP2。该轴可能对晚期PCa具有诊断和治疗潜力。
