Central Laboratory of the First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
The Nanfang Hospital, Guangzhou 510515, China.
Exp Cell Res. 2018 Dec 15;373(1-2):171-179. doi: 10.1016/j.yexcr.2018.10.010. Epub 2018 Oct 19.
MicroRNA (miR) is important regulators of gene expression, and aberrant miR expression has been linked to oncogenesis; however, little is understood about their contribution to colorectal cancer (CRC). Here, we determined that miR-23a is overexpressed in human colorectal cancer cell lines and tissues compared with that of normal cells. The stable over-expression of miR-23a in CRC cells was sufficient to promote cell proliferation in vitro and in vivo. Further studies showed that miR-23a can directly bind to the 3'untranslated region (3'UTR) of PDK4 mRNA and subsequently repress both the mRNA and protein expressions of PDK4. PDK4 negatively regulate CRC proliferation via suppressing PDH activity. Ectopic expression of PDK4 by transiently transfected with PDK4 vector encoding the entire coding sequence could reverse the effects of miR-23a on CRC proliferation. By this way, miR-23a promotes PDH activation and oxidative phosphorylation to generate sufficient ATP for cell proliferation. Our results illustrated that the up-regulation of miR-23a played an important role in CRC cell proliferation through direct repressing PDK4, suggesting a potential application of miR-23a in prognosis prediction and therapeutic application in CRC.
MicroRNA (miR) 是基因表达的重要调控因子，异常的 miR 表达与肿瘤发生有关；然而，人们对它们在结直肠癌（CRC）中的作用知之甚少。在这里，我们确定 miR-23a 在人结直肠癌细胞系和组织中的表达高于正常细胞。CRC 细胞中 miR-23a 的稳定过表达足以促进体外和体内的细胞增殖。进一步的研究表明，miR-23a 可以直接结合 PDK4 mRNA 的 3'非翻译区（3'UTR），随后抑制 PDK4 的 mRNA 和蛋白表达。PDK4 通过抑制 PDH 活性负调节 CRC 增殖。通过瞬时转染 PDK4 载体（编码整个编码序列）表达 PDK4，可以逆转 miR-23a 对 CRC 增殖的影响。通过这种方式，miR-23a 促进 PDH 激活和氧化磷酸化，为细胞增殖产生足够的 ATP。我们的结果表明，miR-23a 的上调通过直接抑制 PDK4 在 CRC 细胞增殖中发挥重要作用，这表明 miR-23a 在 CRC 的预后预测和治疗应用中具有潜在的应用价值。
