title: Hypoxia-inducible miR-152 suppresses the expression of WNT1 and ERBB3, and inhibits the proliferation of cervical cancer cells.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China xueleitang@yeah.net.
authors.forename: Xue-Lei
authors.initials: XL
authors.lastname: Tang
authors.affiliation: Department of Obstetrics and Gynecology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Pathology, Capital Medical University, Beijing 100069, China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Song
authors.affiliation: Department of Cardiology, Daxing Hospital, Capital Medical University, Beijing 102600, China.
authors.forename: Xue-Hong
authors.initials: XH
authors.lastname: Tang
mesh_terms: D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011401:Promoter Regions, Genetic; D020893:Receptor, ErbB-3 / Q000235:genetics* / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051155:Wnt1 Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: C550856:MIRN152 microRNA, human; D035683:MicroRNAs; C495247:WNT1 protein, human; D051155:Wnt1 Protein; C581292:ERBB3 protein, human; D020893:Receptor, ErbB-3
keywords: Hypoxia; cell proliferation; cervical cancer; microRNA