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The differential expression of OCT4 isoforms in cervical carcinoma.

Li SW, Wu XL, Dong CL, Xie XY, Wu JF, Zhang X - PLoS ONE (2015)

Bottom Line: Here, we reported that both nuclear OCT4A and cytoplasmic OCT4B were overexpressed in CC.Moreover, OCT4B enhanced angiogenesis by the upregulation of CD34, VEGF, HIF-1α 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, the Second Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, China.

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-1α 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.

No MeSH data available.


Related in: MedlinePlus

The relative mRNA levels of OCTB and the stem cell-related genes (OCT4A, Sox2, Nanog, Bmi1 and Klf4) in (A) the tumorsphere and differentiated tumorshperes, and (B) ALDHhigh and ALDHlow cells from primary tumors.GAPDH served as a loading control.
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pone.0118033.g002: The relative mRNA levels of OCTB and the stem cell-related genes (OCT4A, Sox2, Nanog, Bmi1 and Klf4) in (A) the tumorsphere and differentiated tumorshperes, and (B) ALDHhigh and ALDHlow cells from primary tumors.GAPDH served as a loading control.

Mentions: We isolated sphere-forming cells (i.e. CCSCs) from primary CC and cultured in suspension at low density in serum-free sphere medium (S1a Fig.). qRT-PCR showed that expression levels of stem markers (OCT4, Sox2 and Nanog Bmi-1, and Klf4) were high in tumorspheres, but then downregulated under differentiation conditions, which verified the stemness signature of tumorspheres formed (Fig. 2A). However, OCT4 was specifically expressed in the nucleus (white arrow) and cytoplasm (red arrowhead) of tumorspheres (S1b and c Fig.), presumably due to a novel OCT4 alternatviely-spliced variant (i.e. OCT4B1). Unlike OCT4A, OCT4B was mainly detected in differentiated tumorsphere cells, but not in tumorshpere (Fig. 2A). Furthermore, ALDH enzymatic activity validated that ALDH1high cells expressed increased levels of OCT4A and other stem-cell-related genes, while ALDH1low cells expressed significantly elevated level of OCT4B (Fig. 2B). Overall, these results suggest that OCT4A but not OCT4B is responsible for maintenance of the stemness properties of CCSCs.


The differential expression of OCT4 isoforms in cervical carcinoma.

Li SW, Wu XL, Dong CL, Xie XY, Wu JF, Zhang X - PLoS ONE (2015)

The relative mRNA levels of OCTB and the stem cell-related genes (OCT4A, Sox2, Nanog, Bmi1 and Klf4) in (A) the tumorsphere and differentiated tumorshperes, and (B) ALDHhigh and ALDHlow cells from primary tumors.GAPDH served as a loading control.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4376746&req=5

pone.0118033.g002: The relative mRNA levels of OCTB and the stem cell-related genes (OCT4A, Sox2, Nanog, Bmi1 and Klf4) in (A) the tumorsphere and differentiated tumorshperes, and (B) ALDHhigh and ALDHlow cells from primary tumors.GAPDH served as a loading control.
Mentions: We isolated sphere-forming cells (i.e. CCSCs) from primary CC and cultured in suspension at low density in serum-free sphere medium (S1a Fig.). qRT-PCR showed that expression levels of stem markers (OCT4, Sox2 and Nanog Bmi-1, and Klf4) were high in tumorspheres, but then downregulated under differentiation conditions, which verified the stemness signature of tumorspheres formed (Fig. 2A). However, OCT4 was specifically expressed in the nucleus (white arrow) and cytoplasm (red arrowhead) of tumorspheres (S1b and c Fig.), presumably due to a novel OCT4 alternatviely-spliced variant (i.e. OCT4B1). Unlike OCT4A, OCT4B was mainly detected in differentiated tumorsphere cells, but not in tumorshpere (Fig. 2A). Furthermore, ALDH enzymatic activity validated that ALDH1high cells expressed increased levels of OCT4A and other stem-cell-related genes, while ALDH1low cells expressed significantly elevated level of OCT4B (Fig. 2B). Overall, these results suggest that OCT4A but not OCT4B is responsible for maintenance of the stemness properties of CCSCs.

Bottom Line: Here, we reported that both nuclear OCT4A and cytoplasmic OCT4B were overexpressed in CC.Moreover, OCT4B enhanced angiogenesis by the upregulation of CD34, VEGF, HIF-1α 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, the Second Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, China.

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-1α 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.

No MeSH data available.


Related in: MedlinePlus