STAT3 influences the characteristics of stem cells in cervical carcinoma

Abstract

The purpose of the study was to investigate the role of the signal transducer and activator of transcription 3 (STAT3), signal transduction protein in regulating the biological characteristics of stem cells in cervical carcinoma. Overexpressed plasmid of STAT3 was constructed and used to transfect SiHa into cervical carcinoma cells. STAT3-targeted specific siRNA was designed and produced. The effects of STAT3 upregulation (or inhibition) on the expression of NANOG, OCT4 and SOX2 markers of stem cells were measured, using western blot analysis and RT-qPCR. In addition, the tumor sphere experiment was also conducted to detect the formation of tumor spheres after the intervention of expression of STAT3 and the expression of STAT3, NANOG, OCT4 and SOX2 was detected in 35 cases of cervical carcinoma tissues and 31 cases of normal cervical tissues using immunohistochemistry. We determined whether the STAT3 overexpression plasmid was successfully constructed using enzyme digestion, PCR for bacterium solution, western blot analysis and RT-qPCR and found that the plasmid met the requirements of subsequent procedures. Compared with the empty plasmid group and STAT3 low expression group, the mRNA and protein expression of markers of stem cells, OCT4, SOX2 and NANOG were significantly elevated in the STAT3 overexpression group with statistically significant differences (P<0.05), the formation ratio of tumor spheres in the STAT3 overexpression group was also significantly higher than those in the other two groups (P<0.05). The positive expression of STAT3, OCT4, NANOG and SOX2 in the cervical squamous carcinoma group was also markedly higher than that in the chronic cervicitis group (P<0.05). This study led us to a conclusion that STAT3 can regulate the characteristics of stem cells in cervical carcinoma, and STAT3, NANOG, OCT4 and SOX2 are highly expressed in cervical squamous carcinoma, thus able to promote the progression of cervical carcinoma.

The organic esterO,O’-diethyl-(S,S)-ethylenediamine-N,N’-di-2-(3-cyclohexyl)propanoate dihydrochloride attenuates murine breast cancer growth and metastasis

“…Recent results reported by Wang H et al [ 40 ] suggested that SOX2 and NANOG are the key downstream proteins of STAT3 signaling pathways in cancer. SOX2 and NANOG are transcription factors and biomarkers for cancer stem cells (CSCs) [ 41 , 42 ].…”

“…In addition, in line with finding that DE-EDCP treatment markedly reduced expression of STAT3 at protein and mRNA level in vitro , immunohistochemistry analysis showed a similar trend for decreased percentage of Y705 phospho-STAT3-positive cells within breast cancer tissue of DE-EDCP treated mice compared to control group, although this difference did not reach statistical significance (Figure 7C and 7D ). A previous report demonstrated that knockdown of STAT3 protein in cervical carcinoma cell line by siRNA reduced mRNA and protein expressions of NANOG and SOX2 [ 40 ]. Accordingly, data obtained from our study indicated that reduction in STAT3 expression after DE-EDCP treatment resulted in significantly lower expression of NANOG and SOX2 mRNA.…”

Pterostilbene Suppresses both Cancer Cells and Cancer Stem-Like Cells in Cervical Cancer with Superior Bioavailability to Resveratrol

“…Recent studies have revealed that STAT3 is an important regulator for self-renewal and survival of CSCs in various tumors [40]. In cervical carcinoma, STAT3 upregulates the stem-like characteristics of cervical cancer cells by increasing the expression of the stemness supporting markers such as Sox2, Oct4, and Nanog [29,30]. Therefore, targeting STAT3 signaling may be a promising approach to combat the survival of cervical CSCs.…”

“…Pterostilbene treatment more noticeably decreased the expression levels of stemness markers compared with resveratrol treatment. The STAT3 pathway is involved in the maintenance of cervical CSCs by regulating the expression of stem cell-related transcription factors [29,30]. To further understand the molecular mechanism underlying the anticancer effects of resveratrol and pterostilbene against cervical CSCs, we investigated whether the two compounds affect STAT3 signaling.…”

Systematic analysis of gene expression alterations and clinical outcomes of STAT3 in cancer

“…Aberrant expression and persistent activation of STAT3 is implicated in cell proliferation, differentiation, apoptosis and immune escape, inducing and maintaining a pro-carcinogenic inflammatory microenvironment [ 7 ]. Continuously activated STAT3 has been found in many human tumors, such as lung cancer [ 8 ], gastric carcinoma [ 9 ], cervical carcinoma [ 10 ], and meningiomas [ 11 ]. Moreover, mounting evidence have demonstrated STAT3-targeted therapy could effectively inhibit tumor development in various human cancers [ 12 ].…”