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微小RNA-23a/27a/24-2簇协同促进胃癌细胞增殖。

MicroRNA-23a/27a/24-2 cluster promotes gastric cancer cell proliferation synergistically.

作者信息

Hua Kate, Chen Yu-Ting, Chen Chian-Feng, Tang Ya-Syuan, Huang Tzu-Ting, Lin Yu-Cheng, Yeh Tien-Shun, Huang Kuo-Hung, Lee Hsin-Chen, Hsu Ming-Ta, Chi Chin-Wen, Wu Chew-Wun, Lin Chi-Hung, Ping Yueh-Hsin

机构信息

Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan, R.O.C.

VYM Genome Research Center, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan, R.O.C.

出版信息

Oncol Lett. 2018 Aug;16(2):2319-2325. doi: 10.3892/ol.2018.8924. Epub 2018 Jun 7.

Abstract

Previous studies have indicated that certain microRNAs (miRNAs/miRs) function as either tumor suppressors or oncogenes in human cancer. The present study identified the miR-23a/27a/24-2 cluster, containing miR-23, miR-27a and miR-24, as an oncogene in gastric cancer. The expression of the miR-23a/27a/24-2 cluster was upregulated in clinical gastric cancer tissues. Transfection with inhibitors of miR-23a, miR-27a, or miR-24, either independently or together, repressed colony formation and tumor formation. The miR23a/27a/24-2 cluster inhibitors repressed the growth of gastric cancer cells in a synergistic manner. In addition, treatment with lower doses of the miRNA inhibitor mixture induced the formation of apoptotic bodies. According to computational predictions using TargetScan, suppressor of cytokine-induced signaling 6 (SOCS6) was identified as one of the downstream target genes of the miR-23a/27a/24-2 cluster. The expression of SOCS6 was significantly lower in tumor tissues than in matched normal tissues (P<0.01) and was associated with poor survival (P<0.00001). Taken together, these results strongly suggested that the miR-23a/27a/24-2 cluster may mediate the progression of gastric cancer through the suppression of SOCS6 expression. The present study also provides a novel molecular target for the development of an anti-gastric cancer agent.

摘要

先前的研究表明,某些微小RNA(miRNA/miR)在人类癌症中发挥肿瘤抑制因子或癌基因的作用。本研究确定包含miR-23、miR-27a和miR-24的miR-23a/27a/24-2簇为胃癌中的一个癌基因。miR-23a/27a/24-2簇在临床胃癌组织中的表达上调。单独或一起转染miR-23a、miR-27a或miR-24的抑制剂,均可抑制集落形成和肿瘤形成。miR23a/27a/24-2簇抑制剂以协同方式抑制胃癌细胞的生长。此外,用较低剂量的miRNA抑制剂混合物处理可诱导凋亡小体的形成。根据使用TargetScan的计算预测,细胞因子诱导信号抑制因子6(SOCS6)被确定为miR-23a/27a/24-2簇的下游靶基因之一。SOCS6在肿瘤组织中的表达明显低于配对的正常组织(P<0.01),且与较差的生存率相关(P<0.00001)。综上所述,这些结果强烈表明miR-23a/27a/24-2簇可能通过抑制SOCS6表达来介导胃癌的进展。本研究还为开发抗胃癌药物提供了一个新的分子靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/217d/6036456/55aa6004657c/ol-16-02-2319-g00.jpg

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