Wei Li-Qiang, Liang Hui-Tao, Qin Dong-Chun, Jin Hui-Fang, Zhao Yong, She Ming-Cong
Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe Road, Zhengzhou, 450052, Henan, China.
Tumour Biol. 2014 Dec;35(12):12427-34. doi: 10.1007/s13277-014-2560-2. Epub 2014 Sep 9.
MicroRNAs (miRNAs) play critical roles in the development and progression of ovarian cancer. We found that miR-212 was significantly downregulated in serum and tissues from epithelial ovarian cancer (EOC) patients. Overexpression of miR-212 in ovarian cancer cells inhibited cell proliferation, migration, and invasion. Luciferase reporter assay confirmed HBEGF as a direct target of miR-212. Overexpression of miR-212 decreased HBEGF expression at both the protein and messenger RNA (mRNA) levels. Knockdown of HBEGF expression in SKOV3 cell line significantly inhibited cell growth, migration, and invasion. HBEGF mRNA level was upregulated in EOC tissues and inversely correlated with miR-212 expression in tissues. Upregulation of HBEGF could attenuate the effect induced by miR-212. These findings indicate that miR-212 displays a tumor-suppressive effect in human ovarian cancer. And miR-212 suppresses cell proliferation, migration, and invasion by targeting the HBEGF transcript, highlighting the therapeutic potential of miR-212 and HBEGF in epithelial ovarian cancer treatment.
微小RNA（miRNA）在卵巢癌的发生发展过程中发挥着关键作用。我们发现，上皮性卵巢癌（EOC）患者血清和组织中的miR-212显著下调。在卵巢癌细胞中过表达miR-212可抑制细胞增殖、迁移和侵袭。荧光素酶报告基因检测证实HBEGF是miR-212的直接靶点。miR-212过表达在蛋白质和信使核糖核酸（mRNA）水平均降低了HBEGF的表达。在SKOV3细胞系中敲低HBEGF表达可显著抑制细胞生长、迁移和侵袭。EOC组织中HBEGF mRNA水平上调，且与组织中miR-212表达呈负相关。上调HBEGF可减弱miR-212诱导的效应。这些发现表明，miR-212在人类卵巢癌中发挥肿瘤抑制作用。并且miR-212通过靶向HBEGF转录本抑制细胞增殖、迁移和侵袭，凸显了miR-212和HBEGF在上皮性卵巢癌治疗中的潜在治疗价值。
