miR-383 inhibits ovarian cancer cell proliferation, invasion and aerobic glycolysis by targeting LDHA
miR-383 inhibits ovarian cancer cell proliferation, invasion and aerobic glycolysis by targeting LDHA
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miR-383 通过靶向 LDHA 抑制卵巢癌细胞增殖、侵袭和有氧糖酵解。
DOI：
10.4149/neo_2017_211
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发表时间：
2017-01-01
期刊：
影响因子：
3
通讯作者：
Li, Y.
中科院分区：
文献类型：
--
作者：
Han, R. L.;Wang, F. P.;Li, Y.
微小RNA（miRNAs）在各种癌症中差异表达，并作为癌基因或肿瘤抑制因子。MiR-383在几种癌症中被表征为癌症抑制剂。然而，miR-383的确切表达模式及其在卵巢癌中作用的确切分子机制尚未得到彻底研究。在本研究中，我们发现miR-383在卵巢癌组织和卵巢癌细胞系中的表达显著下调。miR-383的异位表达通过促进细胞凋亡抑制卵巢癌细胞增殖，显著抑制卵巢癌细胞的侵袭能力，而miR-383的低表达则表现出相反的作用。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LDHA的3 '-非翻译区（3' UTR）抑制LDHA mRNA的表达。卵巢癌组织中miR-383的表达与LDHA呈负相关。此外，调节miR-383表达可影响卵巢癌细胞中的有氧糖酵解。此外，LDHA的沉默抵消了miR-383抑制的作用，而其过表达逆转了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LDHA的表达，从而阻碍糖酵解，细胞增殖和侵袭。
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.