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...
Main Authors: | , , , , , , |
---|---|
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 |
id |
doaj-c227feee3854492d961ae3ded1a856c0 |
---|---|
record_format |
Article |
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 |
work_keys_str_mv |
AT xiaohongwang aberrantexpressionofoncogenicandtumorsuppressivemicrornasincervicalcancerisrequiredforcancercellgrowth AT shuangtang aberrantexpressionofoncogenicandtumorsuppressivemicrornasincervicalcancerisrequiredforcancercellgrowth AT shuyunle aberrantexpressionofoncogenicandtumorsuppressivemicrornasincervicalcancerisrequiredforcancercellgrowth AT robertlu aberrantexpressionofoncogenicandtumorsuppressivemicrornasincervicalcancerisrequiredforcancercellgrowth AT janetsrader aberrantexpressionofoncogenicandtumorsuppressivemicrornasincervicalcancerisrequiredforcancercellgrowth AT craigmeyers aberrantexpressionofoncogenicandtumorsuppressivemicrornasincervicalcancerisrequiredforcancercellgrowth AT zhimingzheng aberrantexpressionofoncogenicandtumorsuppressivemicrornasincervicalcancerisrequiredforcancercellgrowth |
_version_ |
1725955594806886400 |