Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth.

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 abun...

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Main Authors: Xiaohong Wang, Shuang Tang, Shu-Yun Le, Robert Lu, Janet S Rader, Craig Meyers, Zhi-Ming Zheng
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2008-07-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC2438475?pdf=render
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spelling doaj-c227feee3854492d961ae3ded1a856c02020-11-24T21:32:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-07-0137e255710.1371/journal.pone.0002557Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth.Xiaohong WangShuang TangShu-Yun LeRobert LuJanet S RaderCraig MeyersZhi-Ming ZhengMicroRNAs (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.http://europepmc.org/articles/PMC2438475?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Xiaohong Wang
Shuang Tang
Shu-Yun Le
Robert Lu
Janet S Rader
Craig Meyers
Zhi-Ming Zheng
spellingShingle Xiaohong Wang
Shuang Tang
Shu-Yun Le
Robert Lu
Janet S Rader
Craig Meyers
Zhi-Ming Zheng
Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth.
PLoS ONE
author_facet Xiaohong Wang
Shuang Tang
Shu-Yun Le
Robert Lu
Janet S Rader
Craig Meyers
Zhi-Ming Zheng
author_sort Xiaohong Wang
title Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth.
title_short Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth.
title_full Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth.
title_fullStr Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth.
title_full_unstemmed Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth.
title_sort aberrant expression of oncogenic and tumor-suppressive micrornas in cervical cancer is required for cancer cell growth.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2008-07-01
description 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.
url http://europepmc.org/articles/PMC2438475?pdf=render
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