Dataset Information

The differential expression of OCT4 isoforms in cervical carcinoma.

ABSTRACT: OCT4 is a transcription factor involved in maintaining stem cell phenotype and pluripotential. However, it remains unclear the expression pattern and biological function of OCT4 isoforms in cervical cancer. Here, we reported that both nuclear OCT4A and cytoplasmic OCT4B were overexpressed in CC. OCT4A was responsible for self-renewal of cervical cancer stem-like cells (CCSCs). Furthermore, OCT4B overexpression in SiHa cervical cancer cell line significantly increased cell proliferation and tumorigenesis by inhibiting apoptosis. Moreover, OCT4B enhanced angiogenesis by the upregulation of CD34, VEGF, HIF-1? and IL-6, and promoted tumor cell mobility to the surrounding tissue by the upregulation of MMP2 and MMP9, and the induction of epithelial-mesenchymal transition (EMT). In conclusion, nuclear OCT4A may serve as a marker of CCSCs and the driving force for cervical cancer metastasis and recurrence, while cytoplasmic OCT4B may cooperate with OCT4A to regulate the progression of cervical cancer through inducing angiogenesis and EMT.

SUBMITTER: Li SW

PROVIDER: S-EPMC4376746 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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The differential expression of OCT4 isoforms in cervical carcinoma.

Li Shao-Wen SW Wu Xiao-Ling XL Dong Chun-Li CL Xie Xiu-Ying XY Wu Jin-Fang JF Zhang Xin X

PloS one 20150327 3

OCT4 is a transcription factor involved in maintaining stem cell phenotype and pluripotential. However, it remains unclear the expression pattern and biological function of OCT4 isoforms in cervical cancer. Here, we reported that both nuclear OCT4A and cytoplasmic OCT4B were overexpressed in CC. OCT4A was responsible for self-renewal of cervical cancer stem-like cells (CCSCs). Furthermore, OCT4B overexpression in SiHa cervical cancer cell line significantly increased cell proliferation and tumor ...[more]

PMID: 25816351

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Project description:As more small RNA sequencing libraries are becoming available, it clearly emerges that microRNAs (miRNAs) are highly heterogeneous both in length and sequence. In comparison to canonical miRNAs, miRNA isoforms (termed as "isomiRs") might exhibit different biological properties, such as a different target repertoire, or enhanced/reduced stability. Nonetheless, this layer of information has remained largely unexplored due to the scarcity of small RNA NGS-datasets and the absence of proper analytical tools. Here, we present a workflow for the characterization and analysis of miRNAs and their variants in next-generation sequencing datasets. IsomiRs can originate from an alternative dicing event ("templated" forms) or from the addition of nucleotides through an enzymatic activity or target-dependent mechanisms ("non-templated" forms). Our pipeline allows distinguishing canonical miRNAs from templated and non-templated isomiRs by alignment to a custom database, which comprises all possible 3'-, 5'-, and trimmed variants. Functionally equivalent isomiRs can be grouped together according to the type of modification (e.g., uridylation, adenylation, trimming?…) to assess which miRNAs are more intensively modified in a given biological context. When applied to the analysis of primary epithelial breast cancer cells, our methodology provided a 40% increase in the number of detected miRNA species and allowed to easily identify and classify more than 1000 variants. Most modifications were compatible with templated IsomiRs, as a consequence of imprecise Drosha or Dicer cleavage. However, some non-templated variants were consistently found either in the normal or in the cancer cells, with the 3'-end adenylation and uridylation as the most frequent events, suggesting that miRNA post-transcriptional modification frequently occurs. In conclusion, our analytical tool permits the deconvolution of miRNA heterogeneity and could be used to explore the functional role of miRNA isoforms.

Project description:Previous studies have reported the upregulation of stem cell biomarkers that are associated with tumorigenesis, in particular with cancer infiltration, recurrence and metastasis. Infection by human papilloma virus (HPV) is the main etiopathological factor of cervical carcinogenesis, but the expression of stem cell markers in cervical carcinoma and HPV infection have yet to be investigated so far. A total of 94 cases of fresh cervical tissues, 116 cases of paraffin-embedded cervical specimens and 72 cases of peripheral blood samples were collected from Uighur women who were either diagnosed with cervical squamous cell carcinoma (SCC) or cervical intraepithelial neoplasia (CIN) II-III, or from healthy subjects (negative controls, NC). HPV infection was detected in tissue DNA by polymerase chain reaction (PCR) with a HPV genotyping kit. The mRNA expression levels of aldehyde dehydrogenase 1 family member A1 (ALDH1A1), nanog homeobox (NANOG), POU class 5 homeobox 1 (OCT4), SRY-box 2 (SOX2) and twist family BHLH transcription factor 1 (Twist1) were determined using reverse transcription-quantitative PCR (RT-qPCR). Histological analysis was performed in order to examine the protein expression of ALDH1A1 and OCT4 in paraffin-embedded tissue specimens by immunohistochemical staining and the plasma levels of those two proteins was measured by ELISA. RT-qPCR analysis indicated a significant increase in the mRNA expression of ALDH1A1 and OCT4 in CIN II-III and SCC tissue specimens compared with NC (P<0.05). Although the expression levels of NANOG, SOX2 and Twist1 were significantly higher in SCC compared with NC (P<0.05), no significant difference was revealed in CIN II-III tissues compared with SCC or NC (P>0.05). Subsequent analysis by immunohistochemistry staining confirmed that the upregulation of ALDH1A1 and OCT4 was also significantly increased in SCC and CIN II-III compared with controls at the protein level. Notably, ELISA analysis detected significantly higher levels of ALDH1A1 and OCT4 in the peripheral blood (plasma) of patients with SCC compared with healthy subjects. The upregulation of stem cell markers ALDH1A1 and OCT4 in cervical carcinoma and its precursor lesions, in particular in the peripheral blood, indicates that ALDH1A1 and OCT4 may serve as biomarkers for the early detection of cervical carcinoma or for the monitoring of treatment of patients.

Dataset Information

The differential expression of OCT4 isoforms in cervical carcinoma.

Publications

The differential expression of OCT4 isoforms in cervical carcinoma.

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