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微小RNA-1291靶向黏蛋白1,抑制食管鳞状细胞癌的细胞增殖和侵袭,促进细胞凋亡。

miR-1291 targets mucin 1 inhibiting cell proliferation and invasion to promote cell apoptosis in esophageal squamous cell carcinoma.

作者信息

Luo Hailan, Guo Wentao, Wang Fei, You Yanjie, Wang Jianguo, Chen Xudong, Wang Jihong, Wang Yuanyuan, Du Yuwen, Chen Xiaonan, Xue Changgui, Song Guohua, Wang Fuqing

机构信息

Department of Basic Medical Sciences, Luohe Medical College, Luohe, Henan 462002, P.R. China.

College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.

出版信息

Oncol Rep. 2015 Nov;34(5):2665-73. doi: 10.3892/or.2015.4206. Epub 2015 Aug 19.

Abstract

MicroRNAs (miRNAs) are well known as important regulators in various cancer development. In the present study, we focused on the expression and biological function of miR-1291 in esophageal squamous cell carcinoma (ESCC). Compared with adjacent non-tumorous tissue samples, qRT-PCR data showed significant downregulation of miR-1291 in 54 ESCC tissue samples (P<0.05), which was also significantly associated with lymph node metastases and clinical stage (P<0.05). Cell Counting Kit-8 (CCK-8), colony formation, Transwell and flow cytometric apoptosis assays were performed to detect the effect of miR-1291 upregulation, and the results showed inhibition of the proliferation, invasion and promotion of apoptosis in EC9706 and EC-1 cells. Using bioinformatic analyses, we found that mucin 1 (MUC1) was a potential target for miR-1291. Luciferase assays were performed to reveal that miR-1291 inhibited MUC1 expression by targeting the seed region of MUC1 3'-untranslated region (3'UTR). We also found that the expression of MUC1 lacking in 3'UTR abrogated the anti-invasion and pro-apoptosis function of miR-1291. Our results demonstrated the importance of miR-1291 in targeting MUC1 for the regulation of esophagus cancer growth, invasion and apoptosis, and may be helpful for developing new targets for early diagnosis or new therapeutic targets for ESCC.

摘要

微小RNA(miRNA)作为各种癌症发展中的重要调节因子而广为人知。在本研究中,我们聚焦于miR-1291在食管鳞状细胞癌(ESCC)中的表达及生物学功能。与相邻的非肿瘤组织样本相比,qRT-PCR数据显示,在54例ESCC组织样本中miR-1291显著下调(P<0.05),这也与淋巴结转移和临床分期显著相关(P<0.05)。进行细胞计数试剂盒-8(CCK-8)、集落形成、Transwell和流式细胞术凋亡检测以检测miR-1291上调的作用,结果显示其对EC9706和EC-1细胞的增殖、侵袭有抑制作用并促进凋亡。通过生物信息学分析,我们发现黏蛋白1(MUC1)是miR-1291的潜在靶点。进行荧光素酶检测以揭示miR-1291通过靶向MUC1 3'-非翻译区(3'UTR)的种子区域来抑制MUC1表达。我们还发现缺失3'UTR的MUC1的表达消除了miR-1291的抗侵袭和促凋亡功能。我们的结果证明了miR-1291靶向MUC1对调节食管癌生长、侵袭和凋亡的重要性,可能有助于开发早期诊断的新靶点或ESCC的新治疗靶点。

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