Department of Urology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Department of Parasitology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
Biochem Biophys Res Commun. 2018 Sep 26;504(1):171-176. doi: 10.1016/j.bbrc.2018.08.150. Epub 2018 Sep 1.
An increasing number of studies have elucidated the essential roles of long noncoding RNAs (lncRNAs) in tumor development. LncRNAs are also closely associated with bladder cancer (BCa) progression. In the present study, we screened out a novel lncRNA CALML3-AS1 with increased expression value in BCa tissues. Particularly, we showed that CALML3-AS1 overexpression correlates with advanced staging and an unsatisfactory prognosis. Functional experiments illustrated that CALML3-AS1 knockdown suppressed BCa cell proliferation, arrested cell-cycle progression and impaired migration and invasion while promoting apoptosis. Mechanistic investigation revealed that CALML3-AS1 directly interacts with miR-4316 and inhibits its availability in BCa cells, leading to elevated expression of ZBTB2. Consequently, ZBTB2 promotes BCa tumorigenesis through repressing p21 and facilitating PDK4 transcription. In conclusion, our findings demonstrate a novel CALML3-AS1-mediated process involved in BCa progression and indicate it might be a promising therapeutic target.
越来越多的研究阐明了长非编码 RNA（lncRNA）在肿瘤发生中的重要作用。lncRNA 也与膀胱癌（BCa）的进展密切相关。在本研究中，我们筛选出一种新型 lncRNA CALML3-AS1，其在 BCa 组织中的表达值增加。特别地，我们表明 CALML3-AS1 的过表达与晚期分期和预后不良相关。功能实验表明，CALML3-AS1 的敲低抑制了 BCa 细胞的增殖，阻滞了细胞周期的进展，并损害了迁移和侵袭，同时促进了细胞凋亡。机制研究表明，CALML3-AS1 直接与 miR-4316 相互作用，抑制其在 BCa 细胞中的可用性，导致 ZBTB2 的表达升高。因此，ZBTB2 通过抑制 p21 和促进 PDK4 转录促进 BCa 肿瘤发生。总之，我们的研究结果表明了一种新的 CALML3-AS1 介导的参与 BCa 进展的过程，并表明它可能是一个有前途的治疗靶点。
