Tang Xue-Lei, Lin Li, Song Li-Na, Tang Xue-Hong
Department of Obstetrics and Gynecology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
Department of Obstetrics and Gynecology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Exp Biol Med (Maywood). 2016 Jul;241(13):1429-37. doi: 10.1177/1535370215610442. Epub 2015 Oct 28.
Hypoxia has been a research focus in cancer because of its important role in maintaining tumor microenvironments. Previous studies have demonstrated that the expression of several miRNAs was altered under hypoxic conditions, suggesting their crucial roles in the development of cancer. In the present study, the expression of 22 miRNAs reported to be significantly upregulated in cervical cancer tissues was examined. We found that four of these miRNAs were upregulated in response to hypoxia in HeLa cervical cancer cells. MiR-152 was upregulated to the greatest extent and was also found to be upregulated by hypoxia in C33A cells and tumor, but not in non-tumor cervical tissues. Moreover, we found that hypoxia-inducible factor-1α regulated the expression of miR-152 in HeLa cells through a hypoxia-responsive element. A bioinformatic tool predicted that WNT1 and ERBB3 were target genes of miR-152. This was confirmed by dual luciferase assays and Western blots. Overexpression of miR-152 repressed WNT1 and ERBB3 expression and decreased proliferation of HeLa cells. Collectively, these data indicate an important role for miR-152 in regulating the hypoxic response of tumor cells.
由于缺氧在维持肿瘤微环境中发挥重要作用，其一直是癌症研究的焦点。先前的研究表明，在缺氧条件下，几种微小RNA（miRNA）的表达会发生改变，这表明它们在癌症发展中起关键作用。在本研究中，检测了22种据报道在宫颈癌组织中显著上调的miRNA的表达。我们发现，其中四种miRNA在HeLa宫颈癌细胞中因缺氧而上调。miR-152上调幅度最大，并且在C33A细胞和肿瘤中也因缺氧而上调，但在非肿瘤宫颈组织中未上调。此外，我们发现缺氧诱导因子-1α通过缺氧反应元件调节HeLa细胞中miR-152的表达。一种生物信息学工具预测WNT1和ERBB3是miR-152的靶基因。双荧光素酶测定和蛋白质印迹证实了这一点。miR-152的过表达抑制了WNT1和ERBB3的表达，并降低了HeLa细胞的增殖。总体而言，这些数据表明miR-152在调节肿瘤细胞缺氧反应中起重要作用。
