Epithelial-mesenchymal transition (EMT) is an important process in the invasion and metastasis of human cervical carcinoma. The pro-inflammatory cytokine interleukin-6 (IL-6) has been shown as an EMT inducer in multiple carcinomas. However, whether the EMT program can be induced by IL-6 and the mechanisms underlying the IL-6-induced EMT in human cervical carcinoma remain to be determined. In this study, we show that IL-6 receptor (IL-6R) and signal transducer and activator of transcription 3 (Stat3) were highly expressed in human cervical squamous cell carcinoma (CSCC) tissues, and the expression of EMT markers was reversed in well-differentiated and poorly-differentiated human CSCC. Additional experiments showed that IL-6 exposure in cervical carcinoma cell lines induced IL-6R and Stat3 expression, markedly promoted cell growth, and altered cell morphology. The treatment of cervical carcinoma cell lines with IL-6 resulted in downregulation of E-Cadherin and upregulation of Vimentin. Importantly, knockdown of Stat3 significantly reversed the IL-6-induced EMT program, suggesting that Stat3 is necessary for IL-6-induced EMT in the progression of human cervical carcinoma. Moreover, Slug, a member of the Snail family of EMT regulators, was observed to be associated with the expression of Stat3. We concluded that IL-6 plays an important role through Stat3 in the EMT induction and can be a potential therapeutic target and biomarker for human cervical carcinoma.
This work was supported by grants from the National Natural Science Foundation of China (Grant no. 81771549 Jinwei Miao). The authors declare that there is no conflict of interest.
Endometriosis (EMs) is defined as the presence of tissue which somewhat resembles endometrial glands and stroma outside the uterus, and elicits fibrosis. Fibrosis is the main factor resulting in pain and infertility, while the aetiology of endometrial fibrosis is unknown. There is strong evidence from numerous experiments showing that connective tissue growth factor (CCN2) plays a central role in fibrogenesis. Exosomal miR-214-3p can regulate the expression of CCN2 through binding to complementary sites in the 3′ untranslated region. This study aimed to explore the role of exosomal miR-214-3p in endometriosis fibrosis and the relationship between CCN2 and miR-214-3p in endometriosis fibrosis. Our results demonstrated that miR-214-3p was significantly down-regulated and CCN2 was up-regulated in EMs ectopic lesion and stromal cells compared with EMs eutopic and endometrium of patients without endometriosis. Exosomal miR-214-3p can inhibit fibrosis in EMs through targeting CCN2. The results were explored and verified in vitro and in vivo, respectively. Cell co-culture was used to explore the contributions of exosomes to intercellular information transmission of miR-214-3p. The results showed that exosomes play a pivotal role in the transportation of miR-214-3p between cells. Furthermore, level of exosomal miR-214-3p in endometriosis patients' serum was lower than that in patients without endometriosis. In conclusion, exosomal miR-214-3p can inhibit fibrosis in EMs by targeting CCN2. MiR-214-3p may be considered as a bio-marker and has a potential therapeutic effect in EMs.
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