title: Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth.
abstract: MicroRNAs (miRNAs) play important roles in cancer development. By cloning and sequencing of a HPV16(+) CaSki cell small RNA library, we isolated 174 miRNAs (including the novel miR-193c) which could be grouped into 46 different miRNA species, with miR-21, miR-24, miR-27a, and miR-205 being most abundant. We chose for further study 10 miRNAs according to their cloning frequency and associated their levels in 10 cervical cancer- or cervical intraepithelial neoplasia-derived cell lines. No correlation was observed between their expression with the presence or absence of an integrated or episomal HPV genome. All cell lines examined contained no detectable miR-143 and miR-145. HPV-infected cell lines expressed a different set of miRNAs when grown in organotypic raft cultured as compared to monolayer cell culture, including expression of miR-143 and miR-145. This suggests a correlation between miRNA expression and tissue differentiation. Using miRNA array analyses for age-matched normal cervix and cervical cancer tissues, in combination with northern blot verification, we identified significantly deregulated miRNAs in cervical cancer tissues, with miR-126, miR-143, and miR-145 downregulation and miR-15b, miR-16, miR-146a, and miR-155 upregulation. Functional studies showed that both miR-143 and miR-145 are suppressive to cell growth. When introduced into cell lines, miR-146a was found to promote cell proliferation. Collectively, our data indicate that downregulation of miR-143 and miR-145 and upregulation of miR-146a play a role in cervical carcinogenesis.
authors.affiliation: HIV and AIDS Malignancy Branch, Center for Cancer Research, Nation Cancer Institute/National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wang
authors.forename: Shuang
authors.initials: S
authors.lastname: Tang
authors.forename: Shu-Yun
authors.initials: SY
authors.lastname: Le
authors.forename: Robert
authors.initials: R
authors.lastname: Lu
authors.forename: Janet S
authors.initials: JS
authors.lastname: Rader
authors.forename: Craig
authors.initials: C
authors.lastname: Meyers
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Zheng
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: D035683:MicroRNAs