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长链非编码 RNA MINCR 通过激活 Wnt/β-catenin 信号促进口腔鳞状细胞癌中的细胞增殖和迁移。

LncRNA MINCR activates Wnt/β-catenin signals to promote cell proliferation and migration in oral squamous cell carcinoma.

机构信息

Department of Pathology, Nanjing First Hospital, Nanjing Medical University, Changle Road 68, Nanjing 210006, Jiangsu, China.

Department of Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Chengdu, Sichuan 610000, China.

出版信息

Pathol Res Pract. 2019 May;215(5):924-930. doi: 10.1016/j.prp.2019.01.041. Epub 2019 Jan 30.

DOI:10.1016/j.prp.2019.01.041
PMID:30777615
Abstract

Oral squamous cell carcinoma (OSCC) is a common type of malignant oral cancer with high recurrence. MYC-induced long non-coding RNA (MINCR) has been reported as a tumor suppressor in liver cancer and lung cancer. Whereas, it is unknown whether MINCR exerted function in OSCC progression. This study focused on its function and mechanism in OSCC. At first, the expression level of MINCR in OSCC tissues and cell lines as well as corresponding normal controls was evaluated by qRT-PCR assay. The relative high level of MINCR was observed in OSCC tissues and cell lines. The overall survival rate of OSCC patients with high or low level of MINCR was analyzed by using Kaplan-Meier method. In addition, functional assay revealed that MINCR knockdown significantly suppressed OSCC cell proliferation and invasion. Importantly, the effect of MINCR knockdown on Wnt/β-catenin signaling pathway was detected by luciferase reporter and western blot assays. It was found that MINCR knockdown obviously decreased the activity of Wnt/β-catenin pathway. Rescue assays were further used to validate the role of Wnt/β-catenin pathway in MINCR-mediated OSCC progression. The effects of MINCR knockdown on OSCC cell proliferation and migration were partly reversed by the activator of Wnt/β-catenin pathway (LiCl). Overall, our findings revealed that MINCR may be an oncogene in OSCC via modulation of Wnt/β-catenin pathway.

摘要

口腔鳞状细胞癌 (OSCC) 是一种常见的恶性口腔癌,具有较高的复发率。MYC 诱导的长非编码 RNA (MINCR) 已被报道在肝癌和肺癌中作为肿瘤抑制因子。然而,MINCR 是否在 OSCC 进展中发挥作用尚不清楚。本研究重点研究了 MINCR 在 OSCC 中的功能和机制。首先,通过 qRT-PCR 检测 MINCR 在 OSCC 组织和细胞系以及相应的正常对照中的表达水平。结果观察到 MINCR 在 OSCC 组织和细胞系中的相对高水平。采用 Kaplan-Meier 法分析 OSCC 患者 MINCR 高表达或低表达的总生存率。此外,功能测定显示 MINCR 敲低显著抑制 OSCC 细胞的增殖和侵袭。重要的是,通过荧光素酶报告和 Western blot 检测检测到 MINCR 敲低对 Wnt/β-catenin 信号通路的影响。结果发现 MINCR 敲低明显降低了 Wnt/β-catenin 通路的活性。进一步进行挽救实验以验证 Wnt/β-catenin 通路在 MINCR 介导的 OSCC 进展中的作用。Wnt/β-catenin 通路的激活剂 (LiCl) 部分逆转了 MINCR 敲低对 OSCC 细胞增殖和迁移的影响。总体而言,我们的研究结果表明,MINCR 可能通过调节 Wnt/β-catenin 通路成为 OSCC 的癌基因。

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