Department of Integrated Traditional and Western Medicine, Tumor Hospital of Jilin Province, Changchun, Jilin 130012, P.R. China.
Department of Emergency, Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, Jilin 130000, P.R. China.
Mol Med Rep. 2018 Aug;18(2):2269-2276. doi: 10.3892/mmr.2018.9191. Epub 2018 Jun 19.
Previous studies have indicated that overexpression of long noncoding RNA cancer susceptibility 15 (CASC15) may promote tumor development and progression in gastric cancer and hepatocellular carcinoma. However, the function of CASC15 in colon cancer remains unknown. In the present study, the expression of CASC15 was upregulated in colon cancer tissues and its expression was correlated with clinical Tumor‑Node‑Metastasis stage and tumor metastasis. In addition, knockdown of CASC15 significantly inhibited the proliferation, migration and invasion of colon cancer cells in vitro and in vivo. Following mechanistic experiments, CASC15 was observed to act as a sponge to suppress microRNA (miR)‑4310 that targeted LGR5. Through the inhibition of miR‑4310, CASC15 promoted leucine‑rich repeat‑containing G‑protein coupled receptor 5 (LGR5) expression and consequently activated the Wnt/β‑catenin signaling pathway. The results revealed that the inhibition of the Wnt/β‑catenin signaling pathway in CASC15‑overexpressing colon cancer cells suppressed cellular proliferation, migration and invasion. Collectively, these results demonstrated that CASC15 promoted colon cancer growth and metastasis through the activation of the Wnt/β‑catenin signaling pathway in a miR‑4310/LGR5 dependent manner. Thus, the present study suggested that CASC15 may be a therapeutic target for colon cancer treatment.
先前的研究表明,长链非编码 RNA 癌症易感性 15(CASC15)的过表达可能促进胃癌和肝细胞癌的肿瘤发展和进展。然而,CASC15 在结肠癌中的功能尚不清楚。在本研究中,CASC15 在结肠癌组织中上调表达,其表达与临床肿瘤-淋巴结-转移分期和肿瘤转移相关。此外,CASC15 的敲低显著抑制了结肠癌细胞在体外和体内的增殖、迁移和侵袭。通过机制实验,观察到 CASC15 作为海绵抑制靶向 LGR5 的 microRNA(miR)-4310。通过抑制 miR-4310,CASC15 促进富含亮氨酸重复的 G 蛋白偶联受体 5(LGR5)的表达,并进而激活 Wnt/β-连环蛋白信号通路。结果表明,抑制 CASC15 过表达结肠癌细胞中的 Wnt/β-连环蛋白信号通路抑制了细胞增殖、迁移和侵袭。综上所述,这些结果表明 CASC15 通过依赖于 miR-4310/LGR5 的方式激活 Wnt/β-连环蛋白信号通路促进结肠癌的生长和转移。因此,本研究表明 CASC15 可能是结肠癌治疗的一个有前途的治疗靶点。