The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
Biomed Pharmacother. 2018 Nov;107:382-389. doi: 10.1016/j.biopha.2018.07.118. Epub 2018 Aug 9.
Long non-coding RNAs (lncRNAs) regulate diverse cellular processes, and their anomalous expression exert an essential role in the progression of many kinds of cancers, including colorectal carcinoma (CRC). The objective of this study was to investigate the role of lncRNA kcna3 and its underlying mechanism in CRC progression. The expression of lncRNA kcna3 in human CRC tissues and the adjacent non-tumor tissues was evaluated by RT-PCR. The correlations between lncRNA kcna3 expression levels and the overall survival (OS), as well as the clinicopathological features of CRC patients were analyzed. Gain-of-function and loss-of-function experiments were used to evaluate the effects of lncRNA kcna3 on the proliferation, apoptosis, migration, invasion and tumorigenesis of colon cancer SW620 cells. We found that lncRNA kcna3 was lowly expressed in CRC tissues, and its low expression was closely associated with patients' higher TNM grade and the higher occurrence rate of lymphatic metastasis and distant metastasis, as well as shorter OS. Enhanced expression of lncRNA kcna3 inhibited SW620 cells' proliferation, migration and invasion, and induced cell apoptosis in vitro, and repressed CRC tumor growth in vivo. Whereas knockdown of lncRNA kcna3 showed the opposite results. Mechanistically, up-regulation of lncRNA kcna3 decreased YAP1 protein expression and accelerated its degradation. The effects of lncRNA kcna3 overexpression on cell growth and tumorigenesis inhibition and apoptosis promotion were weakened when the expression of YAP1 was up-regulated. In conclusion, this study revealed that lncRNA kcna3 exerts a tumor-inhibit role in CRC progression through down-regulating YAP1 expression, indicating that lncRNA kcna3/YAP1 might be served as a new prognostic biomarker and therapeutic target for CRC.
长链非编码 RNA（lncRNA）调节多种细胞过程，其异常表达在包括结直肠癌（CRC）在内的许多癌症的进展中起着重要作用。本研究旨在探讨 lncRNA kcna3 的作用及其在 CRC 进展中的潜在机制。通过 RT-PCR 评估 lncRNA kcna3 在人 CRC 组织和相邻非肿瘤组织中的表达。分析 lncRNA kcna3 表达水平与 CRC 患者总生存期（OS）以及临床病理特征之间的相关性。通过功能获得和功能丧失实验评估 lncRNA kcna3 对结肠癌细胞 SW620 增殖、凋亡、迁移、侵袭和致瘤性的影响。我们发现 lncRNA kcna3 在 CRC 组织中低表达，其低表达与患者较高的 TNM 分级、较高的淋巴转移和远处转移发生率以及较短的 OS 密切相关。lncRNA kcna3 的表达增强抑制了 SW620 细胞的增殖、迁移和侵袭，并在体外诱导细胞凋亡，体内抑制 CRC 肿瘤生长。而 lncRNA kcna3 的敲低则表现出相反的结果。机制上，lncRNA kcna3 的上调降低了 YAP1 蛋白的表达并加速了其降解。当 YAP1 的表达上调时，lncRNA kcna3 过表达对细胞生长和肿瘤抑制、促进凋亡的作用减弱。综上所述，本研究揭示了 lncRNA kcna3 通过下调 YAP1 表达在 CRC 进展中发挥肿瘤抑制作用，表明 lncRNA kcna3/YAP1 可能作为 CRC 的一个新的预后生物标志物和治疗靶点。
