Wang Xiaoqing, Meng Ran, Hu Qing-Mei
Department of Operation Room, Shangqiu First People's Hospital of Henan, Shangqiu, China.
Department of Urology, Shangqiu First People's Hospital of Henan, Shangqiu, China.
Front Genet. 2020 Mar 3;11:180. doi: 10.3389/fgene.2020.00180. eCollection 2020.
Recent studies suggested that microRNA-3127 (miR-3127) was dysregulated in multiple tumor types and has important roles in tumorigenesis and cancer progression. However, its biological roles and the mechanisms that regulate its expression in bladder cancer (BCA) remain to be determined. The expression level of miR-3127 was measured in BCA tissues and its cellular functions were examined using both and experiments. The interaction between miR-3127 and long non-coding RNA (lncRNA) LINC00319 was explored using RNA immunoprecipitation assay and luciferase reporter assays. We showed that miR-3127 expression was significantly downregulated in human BCA tissues and BCA cell lines. Lower miR-3127 levels were associated with worse survival in BCA patients. The overexpression of miR-3127 impaired BCA cell proliferation and invasion, and the knockdown of miR-3127 enhanced BCA cell proliferation and invasion Importantly, miR-3127 was able to suppress cell growth . We demonstrated that miR-3127 repressed the proliferation and invasion of BCA cells though directly targeted the 3'-UTR of , which served as a novel oncogene in BCA cells. The suppression of cell proliferation and invasion caused by miR-3127 overexpression could be partially abrogated by ectopic expression of RAP2A. Furthermore, high expression of LINC00319 was correlated with adverse survival in BCA patients. LINC00319 could bind directly with miR-3127 and inhibited its expression, and the tumor-promoting effects of LINC00319 could be reversed by re-expression of miR-3127 in BCA cells. Our findings indicated that lncRNA LINC00319-mediated miR-3127 repression promotes BCA progression through the upregulation of RAP2A. The re-introduction of miR-3127 or inhibition of LINC00319 might represent a promising therapeutic strategy for BCA treatment.
近期研究表明，微小RNA-3127（miR-3127）在多种肿瘤类型中表达失调，在肿瘤发生和癌症进展中发挥重要作用。然而，其在膀胱癌（BCA）中的生物学作用及调控其表达的机制仍有待确定。检测了BCA组织中miR-3127的表达水平，并通过体外和体内实验研究了其细胞功能。利用RNA免疫沉淀实验和荧光素酶报告基因实验探究了miR-3127与长链非编码RNA（lncRNA）LINC00319之间的相互作用。我们发现，miR-3127在人BCA组织和BCA细胞系中的表达显著下调。BCA患者中，miR-3127水平较低与较差的生存率相关。miR-3127的过表达会损害BCA细胞的增殖和侵袭能力，而敲低miR-3127则会增强BCA细胞的增殖和侵袭能力。重要的是，miR-3127能够抑制细胞生长。我们证明，miR-3127通过直接靶向RAP2A的3'-UTR抑制BCA细胞的增殖和侵袭，RAP2A在BCA细胞中作为一种新型癌基因发挥作用。异位表达RAP2A可部分消除miR-3127过表达引起的细胞增殖和侵袭抑制。此外，LINC00319的高表达与BCA患者的不良生存率相关。LINC00319可直接与miR-3127结合并抑制其表达，在BCA细胞中重新表达miR-3127可逆转LINC00319的促肿瘤作用。我们的研究结果表明，lncRNA LINC00319介导的miR-3127抑制通过上调RAP2A促进BCA进展。重新引入miR-3127或抑制LINC00319可能是一种有前景的BCA治疗策略。
