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微小RNA-142-5p通过靶向琥珀酸脱氢酶复合物亚基B并促进有氧糖酵解的产生来促进结直肠癌的发展。

miR-142-5p promotes development of colorectal cancer through targeting SDHB and facilitating generation of aerobic glycolysis.

作者信息

Liu Shaojun, Xiao Zhiming, Ai Feiyan, Liu Fen, Chen Xiong, Cao Ke, Ren Weiguo, Zhang Xuemei, Shu Peng, Zhang Decai

机构信息

Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha 410013 Hunan, China.

Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha 410013 Hunan, China; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha 410013 Hunan, China.

出版信息

Biomed Pharmacother. 2017 Aug;92:1119-1127. doi: 10.1016/j.biopha.2017.05.134. Epub 2017 Jun 12.

Abstract

Aberrant expression of miRNAs contributes to the development of human malignancies. A recent study revealed that miR-142-5p is increased in the serum of colorectal cancer (CRC) patients compared to health people. Using starBase v2.0, we found that succinate dehydrogenase-B (SDHB) is a potential target of miR-142-5p, while SDHB is negatively correlated to cancer development through regulating energetic metabolism. Based on these information, this study further examined the expression profiles of miR-142-5p and SDHB in CRC tissues and cell lines using PCR and Western blotting. Transfection experiment and luciferase assay were performed to identify relationship between miR-142-5p and SDHB. Oxygen intake, glucose consumption and production of lactic acid were used to evaluate the influence on energetic metabolism. CRC growth and proliferation were assessed by in vitro and in vivo studies. Results showed that miR-142-5p was up-regulated in CRC, but SDHB was down-regulated. SDHB was confirmed as a target of miR-142-5p, and decreased SDHB in CRC was result from the abnormal up-regulation of miR-142-5p. Lose of SDHB by miR-142-5p inhibited oxygen intake by CRC cells, but increased glucose consumption and lactate production. These suggest miR-142-5p up-regulation in CRC probably facilitates generation of aerobic glycolysis by reducing SDHB. miR-142-5p promoted proliferation and colony formation of CRC, but inhibited apoptosis. SDHB overexpression abrogated these effect of miR-142-5p, which indicates that SDHB depletion mediates tumor-promoting actions of miR-142-5p. This study added novel insight into the CRC development regulated by miR-142-5p. It may be a promising therapy target in the future molecular therapy.

摘要

微小RNA(miRNA)的异常表达有助于人类恶性肿瘤的发展。最近一项研究表明,与健康人相比,结直肠癌(CRC)患者血清中的miR-142-5p水平升高。使用starBase v2.0,我们发现琥珀酸脱氢酶-B(SDHB)是miR-142-5p的潜在靶标,而SDHB通过调节能量代谢与癌症发展呈负相关。基于这些信息,本研究进一步使用聚合酶链反应(PCR)和蛋白质免疫印迹法检测了CRC组织和细胞系中miR-142-5p和SDHB的表达谱。进行转染实验和荧光素酶测定以确定miR-142-5p与SDHB之间的关系。通过测量氧气摄取、葡萄糖消耗和乳酸生成来评估对能量代谢的影响。通过体外和体内研究评估CRC的生长和增殖。结果显示,CRC中miR-142-5p上调,但SDHB下调。SDHB被证实为miR-142-5p的靶标,CRC中SDHB的减少是miR-142-5p异常上调的结果。miR-142-5p导致的SDHB缺失抑制了CRC细胞的氧气摄取,但增加了葡萄糖消耗和乳酸生成。这些结果表明,CRC中miR-142-5p的上调可能通过降低SDHB促进有氧糖酵解的产生。miR-142-5p促进了CRC的增殖和集落形成,但抑制了细胞凋亡。SDHB的过表达消除了miR-142-5p的这些作用,这表明SDHB的缺失介导了miR-142-5p的促肿瘤作用。本研究为miR-142-5p调控的CRC发展增添了新的见解。它可能是未来分子治疗中有前景的治疗靶点。

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