Department of Urology, Ningbo No. 2 Hospital, Ningbo, China.
J Cell Mol Med. 2019 Feb;23(2):865-876. doi: 10.1111/jcmm.13986. Epub 2018 Nov 5.
Long noncoding RNAs (lncRNAs) have been proved to play important roles in carcinogenesis and development of numerous cancers, but their biological functions in bladder cancer remain largely unknown. In this study, a novel lncRNA termed GAS6-AS2 were primary identified, and its roles as well as mechanisms in regulating proliferation and metastasis of bladder cancer cells were investigated. Clinically, GAS6-AS2 was significantly up-regulated in bladder cancer tissues and positively correlated with tumour stages and poor prognosis. Moreover, expression of GAS6-AS2 was also increased in bladder cancer cells compared with normal bladder cells. Further investigating the roles of GAS6-AS2, we found GAS6-AS2 regulated proliferation and proliferative activity of bladder cancer cells via inducing G1 phase arrest. What's more, we found that GAS6-AS2 contributed to metastatic abilities of cells. In mechanism, GAS6-AS2 could function as a competitive endogenous RNA (ceRNA) via direct sponging miR-298, which further regulating the expression of CDK9. Finally, we also proved that GAS6-AS2 knockdown suppressed tumour growth and metastasis in vivo. In conclusion, our study proved that GAS6-AS2 could function as a ceRNA and promote the proliferation and metastasis of bladder cancer cells, which provided a novel prognostic marker for bladder cancer patients in clinic.
长链非编码 RNA（lncRNAs）已被证明在许多癌症的发生和发展中发挥重要作用，但它们在膀胱癌中的生物学功能仍知之甚少。在这项研究中，我们初步鉴定了一个新型的 lncRNA 称为 GAS6-AS2，并研究了其在调节膀胱癌细胞增殖和转移中的作用和机制。临床上，GAS6-AS2 在膀胱癌组织中明显上调，并与肿瘤分期和预后不良呈正相关。此外，与正常膀胱细胞相比，膀胱癌细胞中的 GAS6-AS2 表达也增加。进一步研究 GAS6-AS2 的作用，我们发现 GAS6-AS2 通过诱导 G1 期阻滞来调节膀胱癌细胞的增殖和增殖活性。更重要的是，我们发现 GAS6-AS2 有助于细胞的转移能力。在机制上，GAS6-AS2 可以作为竞争性内源性 RNA（ceRNA）通过直接海绵 miR-298 来发挥作用，从而进一步调节 CDK9 的表达。最后，我们还证明了 GAS6-AS2 敲低抑制了体内肿瘤的生长和转移。总之，我们的研究证明 GAS6-AS2 可以作为 ceRNA 促进膀胱癌细胞的增殖和转移，为临床膀胱癌患者提供了一个新的预后标志物。
