Liang Hong, Zhao Qiuyan, Zhu Zhonglin, Zhang Chao, Zhang Hui
Department of Gastrointestinal Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, 450003, Henan, China.
Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Cancer Cell Int. 2021 Sep 8;21(1):477. doi: 10.1186/s12935-021-02188-0.
Long noncoding RNAs (lncRNAs) have been elucidated to participate in the development and progression of various cancers. In this study, we aimed to explore the underlying functions and mechanisms of LINC00958 in colorectal cancer.
LINC00958 expression in colorectal cancer tissues was examined by qRT-PCR. The correlations between LINC00958 expression and clinical characteristics and prognosis were evaluated. The biological functions of LINC00958 were detected by CCK-8, MTT, colony formation and flow cytometric analyses. RNA pulldown, RIP and luciferase reporter assays were used to confirm the regulatory effects of LINC00958 on miR-422a. Rescue experiments were performed to detect the effects of miR-422a on the roles of LINC00958.
LINC00958 was upregulated in colorectal cancer tissues and cell lines. High LINC00958 levels were positively associated with T stage and predicted poor prognosis. Cell experiments showed that LINC00958 promoted cell proliferation and suppressed apoptosis and sensitivity to radiotherapy in vitro and promoted tumor growth in vivo. Bioinformatics analysis predicted the binding site of miR-422a on LINC00958. Mechanistically, RNA pulldown, RIP and luciferase reporter assays demonstrated that LINC00958 specifically targeted miR-422a. In addition, we found that miR-422a suppressed MAPK1 expression by directly binding to the 3'-UTR of MAPK1, thereby inhibiting cell proliferation and enhancing cell apoptosis and radiosensitivity. Furthermore, miR-422a rescued the roles of LINC00958 in promoting MAPK1 expression and cell proliferation and decreasing cell apoptosis and radiosensitivity.
LINC00958 promoted MAPK1 expression and cell proliferation and suppressed cell apoptosis and radiosensitivity by targeting miR-422a, which suggests that it is a potential biomarker for the prognosis and treatment of colorectal cancer.
长链非编码RNA（lncRNAs）已被证实参与多种癌症的发生和发展。在本研究中，我们旨在探究LINC00958在结直肠癌中的潜在功能及机制。
采用qRT-PCR检测结直肠癌组织中LINC00958的表达。评估LINC00958表达与临床特征及预后的相关性。通过CCK-8、MTT、集落形成和流式细胞术分析检测LINC00958的生物学功能。采用RNA下拉、RIP和荧光素酶报告基因检测法确认LINC00958对miR-422a的调控作用。进行挽救实验以检测miR-422a对LINC00958作用的影响。
LINC00958在结直肠癌组织和细胞系中上调。LINC00958高水平与T分期呈正相关，并预示预后不良。细胞实验表明，LINC00958在体外促进细胞增殖、抑制凋亡及放疗敏感性，在体内促进肿瘤生长。生物信息学分析预测了miR-422a在LINC00958上的结合位点。机制上，RNA下拉、RIP和荧光素酶报告基因检测表明LINC00958特异性靶向miR-422a。此外，我们发现miR-422a通过直接结合MAPK1的3'-UTR抑制MAPK1表达，从而抑制细胞增殖并增强细胞凋亡和放射敏感性。此外，miR-422a挽救了LINC00958在促进MAPK1表达和细胞增殖以及降低细胞凋亡和放射敏感性方面的作用。
LINC00958通过靶向miR-422a促进MAPK1表达和细胞增殖，抑制细胞凋亡和放射敏感性，这表明它是结直肠癌预后和治疗的潜在生物标志物。
