Zheng Zhixiong, Qiu Kaiyan, Huang Weiwen
Urology Department, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian 362000, People's Republic of China.
Cancer Manag Res. 2021 Feb 2;13:913-923. doi: 10.2147/CMAR.S270144. eCollection 2021.
Studies have confirmed that parts of the non-coding genes in the human genome play an important role in the pathogenesis and metastasis of prostate cancer. Among them, long non-coding RNAs (lncRNAs) are vitally involved in the biological regulation of prostate cancer. In addition, lncRNAs are closely associated with the recurrence, metastasis and prognosis of prostate cancer. However, the molecular pathogenesis of lncRNAs in regulating cell growth and metastasis of prostate cancer remains unclear. Therefore, this study was designed to explore the function and mechanism of lncRNA RAMS11 in cell growth and metastasis of prostate cancer.
Prostate cancer and para-carcinoma tissue samples were obtained from 42 patients who were diagnosed from March 2013 to September 2014 at Quanzhou First Hospital Affiliated to Fujian Medical University. Microarray experiments and real-time polymerase chain reaction (PCR) measured the expression of lncRNA. RWPE-2, LNCap, PC3 and DU145 cells were used for an in vitro model.
The expression of lncRNA RAMS11 was up-regulated in prostate cancer tissue samples. LncRNA RAMS11 promoted cell growth and metastasis of prostate cancer cells. Down-regulation of lncRNA RAMS11 attenuated cell growth and metastasis of prostate cancer cells. We also demonstrated that lncRNA RAMS11 bound to CBX4 to activate expression of Top2α. LncRNA RAMS11 promoted tumor growth of prostate cancer in the mouse model. The inhibition of CBX4 attenuated the pro-cancer effects of lncRNA AMS11 in prostate cancer cells, while the activation of Top2α attenuated the anti-cancer effects of si-lncRNA RAMS11 in prostate cancer cells.
Our results indicated that lncRNA RAMS11 promoted cell growth and metastasis of prostate cancer by CBX4 complex via binding to Top2α, and might be developed for the treatment of prostate cancer.
研究证实,人类基因组中的部分非编码基因在前列腺癌的发病机制和转移过程中发挥着重要作用。其中,长链非编码RNA(lncRNAs)在前列腺癌的生物学调控中至关重要。此外,lncRNAs与前列腺癌的复发、转移及预后密切相关。然而,lncRNAs在调节前列腺癌细胞生长和转移中的分子发病机制仍不清楚。因此,本研究旨在探讨lncRNA RAMS11在前列腺癌细胞生长和转移中的功能及机制。
从2013年3月至2014年9月在福建医科大学附属泉州第一医院确诊的42例患者中获取前列腺癌及癌旁组织样本。通过微阵列实验和实时聚合酶链反应(PCR)检测lncRNA的表达。使用RWPE-2、LNCap、PC3和DU145细胞建立体外模型。
lncRNA RAMS11在前列腺癌组织样本中的表达上调。lncRNA RAMS11促进前列腺癌细胞的生长和转移。lncRNA RAMS11表达下调可减弱前列腺癌细胞的生长和转移。我们还证明lncRNA RAMS11与CBX4结合以激活Top2α的表达。lncRNA RAMS11在小鼠模型中促进前列腺癌的肿瘤生长。抑制CBX4可减弱lncRNA AMS11在前列腺癌细胞中的促癌作用,而激活Top2α可减弱si-lncRNA RAMS11在前列腺癌细胞中的抗癌作用。
我们的结果表明,lncRNA RAMS11通过与Top2α结合的CBX4复合物促进前列腺癌细胞的生长和转移,可能可用于前列腺癌的治疗。