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Article: miR-135a leads to cervical cancer cell transformation through regulation of β-catenin via a SIAH1-dependent ubiquitin proteosomal pathway

TitlemiR-135a leads to cervical cancer cell transformation through regulation of β-catenin via a SIAH1-dependent ubiquitin proteosomal pathway
Authors
Issue Date2014
PublisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
Citation
Carcinogenesis, 2014, v. 35 n. 9, p. 1931-1940 How to Cite?
AbstractHuman papillomaviruses (HPVs) is the principal etiological agent of cervical cancer (CC). However, exposure to the high-risk type HPV alone is insufficient for tumor formation, and additional factors are required for the HPV-infected cells to become tumorigenic. Dysregulated microRNAs (miRNAs) expression is frequently observed in cancer but their roles in the formation of CC have not been fully revealed. In this study, we compared the expression of miR-135a in laser capture microdissected cervical specimens and confirmed overexpression of the miRNA in malignant cervical squamous cell carcinoma compared with precancerous lesions. Transient force-expression of miR-135a induced growth in low-density culture, anchorage-independent growth, proliferation and invasion of a HPV-16 E6/E7-immortalized cervical epithelial cell line, NC104-E6/E7. The observed effects were due to the inhibitory action of miR-135a on its direct target seven in absentia homolog 1 (SIAH1) leading to upregulation of beta-catenin/T cell factor signaling. miR-135a force-expression enhanced the growth of HeLa- and NC104-E6/E7-derived tumor in vivo. The effect of miR-135a could be partially nullified by SIAH1 force-expression. More importantly, the expression of SIAH1 and beta-catenin correlated with that of miR-135a in precancerous and cancerous lesions of cervical biopsies. By comparing the tumorigenic activities of miR-135a in E6/E7 positive/negative cell lines and in NC104-E6/E7 with or without E6/E7 knockdown, we demonstrated that HPV E6/E7 proteins are prerequisite for miR-135a as an oncomiR. Taken together, miR-135a/SIAH1/beta-catenin signaling is important in the transformation and progression of cervical carcinoma.
Persistent Identifierhttp://hdl.handle.net/10722/200449
ISSN
2015 Impact Factor: 4.874
2015 SCImago Journal Rankings: 2.439
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLEUNG, CON-
dc.contributor.authorDeng, W-
dc.contributor.authorYe, TM-
dc.contributor.authorNgan, HYS-
dc.contributor.authorTsao, GSW-
dc.contributor.authorCheung, ANY-
dc.contributor.authorPang, RTK-
dc.contributor.authorYeung, WSB-
dc.date.accessioned2014-08-21T06:46:35Z-
dc.date.available2014-08-21T06:46:35Z-
dc.date.issued2014-
dc.identifier.citationCarcinogenesis, 2014, v. 35 n. 9, p. 1931-1940-
dc.identifier.issn0143-3334-
dc.identifier.urihttp://hdl.handle.net/10722/200449-
dc.description.abstractHuman papillomaviruses (HPVs) is the principal etiological agent of cervical cancer (CC). However, exposure to the high-risk type HPV alone is insufficient for tumor formation, and additional factors are required for the HPV-infected cells to become tumorigenic. Dysregulated microRNAs (miRNAs) expression is frequently observed in cancer but their roles in the formation of CC have not been fully revealed. In this study, we compared the expression of miR-135a in laser capture microdissected cervical specimens and confirmed overexpression of the miRNA in malignant cervical squamous cell carcinoma compared with precancerous lesions. Transient force-expression of miR-135a induced growth in low-density culture, anchorage-independent growth, proliferation and invasion of a HPV-16 E6/E7-immortalized cervical epithelial cell line, NC104-E6/E7. The observed effects were due to the inhibitory action of miR-135a on its direct target seven in absentia homolog 1 (SIAH1) leading to upregulation of beta-catenin/T cell factor signaling. miR-135a force-expression enhanced the growth of HeLa- and NC104-E6/E7-derived tumor in vivo. The effect of miR-135a could be partially nullified by SIAH1 force-expression. More importantly, the expression of SIAH1 and beta-catenin correlated with that of miR-135a in precancerous and cancerous lesions of cervical biopsies. By comparing the tumorigenic activities of miR-135a in E6/E7 positive/negative cell lines and in NC104-E6/E7 with or without E6/E7 knockdown, we demonstrated that HPV E6/E7 proteins are prerequisite for miR-135a as an oncomiR. Taken together, miR-135a/SIAH1/beta-catenin signaling is important in the transformation and progression of cervical carcinoma.-
dc.languageeng-
dc.publisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/-
dc.relation.ispartofCarcinogenesis-
dc.titlemiR-135a leads to cervical cancer cell transformation through regulation of β-catenin via a SIAH1-dependent ubiquitin proteosomal pathway-
dc.typeArticle-
dc.identifier.emailDeng, W: wdeng@hkucc.hku.hk-
dc.identifier.emailYe, TM: drytm@hkusua.hku.hk-
dc.identifier.emailNgan, HYS: hysngan@hkucc.hku.hk-
dc.identifier.emailTsao, GSW: gswtsao@hku.hk-
dc.identifier.emailCheung, ANY: anycheun@hkucc.hku.hk-
dc.identifier.emailPang, RTK: rtkpang@hku.hk-
dc.identifier.emailYeung, WSB: wsbyeung@hkucc.hku.hk-
dc.identifier.authorityDeng, W=rp01640-
dc.identifier.authorityNgan, HYS=rp00346-
dc.identifier.authorityTsao, GSW=rp00399-
dc.identifier.authorityCheung, ANY=rp00542-
dc.identifier.authorityPang, RTK=rp01761-
dc.identifier.authorityYeung, WSB=rp00331-
dc.identifier.doi10.1093/carcin/bgu032-
dc.identifier.pmid24503442-
dc.identifier.scopuseid_2-s2.0-84906831740-
dc.identifier.hkuros232111-
dc.identifier.volume35-
dc.identifier.issue9-
dc.identifier.spage1931-
dc.identifier.epage1940-
dc.identifier.isiWOS:000345829200003-
dc.publisher.placeUnited Kingdom-

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