Neoplasma. 2017;64(2):244-252. doi: 10.4149/neo_2017_211.
MicroRNAs (miRNAs) are differentially expressed in various cancers and act as oncogenes or tumor suppressors. MiR-383 has been characterized as a cancer suppressor in several cancers. However, the exact expression patterns of miR-383 and the precise molecular mechanisms underlying its role in ovarian cancer have not been investigated thoroughly. In this study, we found that the expression of miR-383 was significantly downregulated in ovarian cancer tissues and ovarian cancer cell lines. Ectopic expression of miR-383 remarkably suppressed the ovarian cancer cell proliferation by enhancing cell apoptosis and significantly inhibited the invasion of ovarian cancer cells, while low expression of miR-383 exhibited the opposite effect. Bioinformatics analysis suggested LDHA as a novel target of miR-383, and miR-383 suppressed the expression level of LDHA mRNA by direct binding to its 3'-untranslated region (3'UTR). Expression of miR-383 was negatively correlated with LDHA in ovarian cancer tissues. In addition, modulation of miR-383 expression could affect the aerobic glycolysis in the ovarian cancer cells. Furthermore, Silencing of LDHA counteracted the effects of miR-383 suppression, while its overexpression reversed tumor inhibitory effects of miR-383. In conclusion, our study demonstrated that miR-383 regulated LDHA expression in ovarian cancer cells, thereby stunting glycolysis, cell proliferation and invasion.
微小 RNA（miRNA）在各种癌症中表达差异，作为癌基因或肿瘤抑制因子发挥作用。miR-383 已被确定为几种癌症中的肿瘤抑制因子。然而，miR-383 的确切表达模式及其在卵巢癌中作用的精确分子机制尚未得到充分研究。在这项研究中，我们发现 miR-383 在卵巢癌组织和卵巢癌细胞系中的表达明显下调。miR-383 的异位表达通过增强细胞凋亡显著抑制卵巢癌细胞的增殖，并显著抑制卵巢癌细胞的侵袭，而 miR-383 的低表达则表现出相反的效果。生物信息学分析表明 LDHA 是 miR-383 的一个新靶点，miR-383 通过直接结合其 3'非翻译区（3'UTR）抑制 LDHA mRNA 的表达水平。miR-383 在卵巢癌组织中的表达与 LDHA 呈负相关。此外，miR-383 表达的调节可以影响卵巢癌细胞中的有氧糖酵解。此外，沉默 LDHA 可以抵消 miR-383 抑制的作用，而过表达 LDHA 则可以逆转 miR-383 的肿瘤抑制作用。总之，我们的研究表明，miR-383 调节卵巢癌细胞中的 LDHA 表达，从而抑制糖酵解、细胞增殖和侵袭。
