Department of Clinical Laboratory, The Fourth Hospital of Xi'an, Xi'an, China.
Department of Clinical Laboratory, The First Affiliated Hospital of Air Force Military Medical University, Xi'an, China.
Neoplasma. 2020 Jul;67(4):825-833. doi: 10.4149/neo_2020_190730N687. Epub 2020 Apr 16.
Ovarian cancer is one of the most common malignancies in women in the world. MicroRNAs (miRNAs) were identified as a group of regulators that played important roles in the progression of cancer development. The main purpose of this study was to investigate the functional mechanism of microRNA-193a-5p (miR-193a-5p) in human ovarian cancer. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the RNA levels of miR-193a-5p and homeobox genes A7 (HOXA7). Western blot assay was performed to determine the protein level of HOXA7. The interaction between miR-193a-5p and HOXA7 was predicted by online software starBase v3.0, and then verified by the dual luciferase reporter assay. The cell proliferation and apoptosis rate were examined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and colony formation assay as well as flow cytometry analysis. We found out that the expression level of miR-193a-5p was decreased in human ovarian cancer tissues and cells. The overexpression of miR-193a-5p inhibited cell proliferation and induced apoptosis in human ovarian cancer. Interestingly, miR-193a-5p reduced the expression of HOXA7 by binding to 3'-untranslated region (3'-UTR) of HOXA7 mRNA. As expected, the knockdown of HOXA7 also suppressed cell proliferation and promoted apoptosis in human ovarian cancer. Besides, the upregulation of HOXA7 reversed the effect of miR-193a-5p on human ovarian cell proliferation and apoptosis. Our findings confirmed that miR-193a-5p inhibited cell proliferation and induced apoptosis through the downregulation of HOXA7 in human ovarian cancer, providing a theoretical value for the therapy of human ovarian cancer.
卵巢癌是全球女性最常见的恶性肿瘤之一。微小 RNA（miRNAs）被鉴定为一组在癌症发展过程中发挥重要作用的调控因子。本研究的主要目的是探讨微小 RNA-193a-5p（miR-193a-5p）在人卵巢癌中的功能机制。采用实时定量聚合酶链反应（qRT-PCR）检测 miR-193a-5p 和同源盒基因 A7（HOXA7）的 RNA 水平。采用 Western blot 检测 HOXA7 的蛋白水平。通过在线软件 starBase v3.0 预测 miR-193a-5p 和 HOXA7 之间的相互作用，然后通过双荧光素酶报告基因检测进行验证。通过 3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2-H-四唑溴盐（MTT）和集落形成实验以及流式细胞术分析检测细胞增殖和凋亡率。我们发现 miR-193a-5p 在人卵巢癌组织和细胞中的表达水平降低。miR-193a-5p 的过表达抑制人卵巢癌细胞的增殖并诱导其凋亡。有趣的是，miR-193a-5p 通过结合 HOXA7 mRNA 的 3'-非翻译区（3'-UTR）降低 HOXA7 的表达。正如预期的那样，HOXA7 的敲低也抑制了人卵巢癌细胞的增殖并促进了其凋亡。此外，HOXA7 的上调逆转了 miR-193a-5p 对人卵巢细胞增殖和凋亡的影响。我们的研究结果证实，miR-193a-5p 通过下调 HOXA7 抑制人卵巢癌细胞的增殖并诱导其凋亡，为人类卵巢癌的治疗提供了理论价值。
