miR-142-5p promotes development of colorectal cancer through targeting SDHB and facilitating generation of aerobic glycolysis
miR-142-5p promotes development of colorectal cancer through targeting SDHB and facilitating generation of aerobic glycolysis
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miR-142-5p通过靶向SDHB并促进有氧糖酵解的产生促进结直肠癌的发展
DOI：
10.1016/j.biopha.2017.05.134
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发表时间：
2017-08-01
影响因子：
7.5
通讯作者：
Zhang, Decai
中科院分区：
文献类型：
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作者：
Liu, Shaojun;Xiao, Zhiming;Zhang, Decai
miRNA 的异常表达有助于人类恶性肿瘤的发展。最近的一项研究表明，与健康人相比，结直肠癌 (CRC) 患者血清中的 miR-142-5p 有所增加。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，本研究进一步利用PCR和Western blotting检测了CRC组织和细胞系中miR-1425p和SDHB的表达谱。进行转染实验和荧光素酶测定来鉴定miR-142-5p和SDHB之间的关系。使用氧摄入量、葡萄糖消耗量和乳酸产生量来评估对能量代谢的影响。通过体外和体内研究评估结直肠癌的生长和增殖。结果显示，miR-142-5p 在 CRC 中上调，但 SDHB 下调。 SDHB 被证实是 miR-142-5p 的靶标，CRC 中 SDHB 的降低是由于 miR142-5p 的异常上调所致。 miR-142-5p 导致的 SDHB 缺失抑制了 CRC 细胞的氧气摄入，但增加了葡萄糖消耗和乳酸产生。这些表明 CRC 中 miR-142-5p 的上调可能通过减少 SDHB 促进有氧糖酵解的产生。 miR-142-5p促进CRC的增殖和集落形成，但抑制细胞凋亡。 SDHB 过表达消除了 miR-142-5p 的这些作用，这表明 SDHB 耗竭介导 miR-142-5p 的肿瘤促进作用。这项研究为 miR-142-5p 调节的 CRC 发展提供了新的见解。它可能是未来分子治疗中一个有前途的治疗靶点。(C) 2017 Elsevier Masson SAS。版权所有。
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-1425p 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 miR142- 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.(C) 2017 Elsevier Masson SAS. All rights reserved.