SummaryEndometrial injury is an important cause of intrauterine adhesion (IUA), amenorrhea and infertility in women, with limited effective therapies. Recently, stem cells have been used in animal experiments to repair and improve injured endometrium. To date, our understanding of adipose-derived stem cells (ADSCs) in endometrial injury repair and their further therapeutic mechanisms is incomplete. Here, we examined the benefit of ADSCs in restoration of injured endometrium by applying a rat endometrial injury model. The results revealed by immunofluorescence showed that green fluorescent protein (GFP)-labelled ADSCs can differentiate into endometrial epithelial cells in vivo. At 30 days after ADSCs transplantation, injured endometrium was significantly improved, with increased microvessel density, endometrial thickness and glands when compared with the model group. Furthermore, the fertility of rats with injured endometrium in ADSCs group was improved and had a higher conception rate (60% vs 20%, P = 0.014) compared with the control phosphate-buffered saline (PBS) group. However, there was no difference in the control group compared with the sham group. In addition, expression levels of the oestrogen receptor Eα/β (ERα, ERβ) and progesterone receptor (PR) detected by western blot and enzyme-linked immunosorbent assay (ELISA) were higher in the ADSCs group than in the PBS group. Taken together, these results suggested that ADSC transplantation could improve endometrial injury as a novel therapy for IUA.
MicroRNAs (miRNAs) play important roles in the processes of tumor initiation and progression. However, miR-145 expression in cervical cancer has been rarely investigated. The aim of this study was to investigate the clinical significance and prognostic value of miR-145 expression in cervical cancer. MiR-145 expression in 114 pairs of human cervical cancer and adjacent normal tissues was detected by real-time quantitative RT-PCR assay. The results showed that miR-145 expression was significantly downregulated in cervical cancer tissues when compared with corresponding adjacent normal tissues (P < 0.001). It was also significantly lower in the cancerous tissues of patients with advanced International Federation of Gynecology and Obstetrics (FIGO) stage cervical cancer than those with early FIGO stage (P = 0.006). In addition, miR-145 was expressed at significantly lower levels in lymph node metastasis-positive patients than in lymph node metastasis-negative patients (P = 0.037). Moreover, poorly differentiated tumors expressed lower miR-145 than well or moderately differentiated tumors (P = 0.012). Patients with vascular invasion or human papillomavirus (HPV) infection also had lower miR-145 expression levels than those without (P = 0.016 and P = 0.025, respectively). Furthermore, Kaplan-Meier analysis showed that cervical cancer patients with low miR-145 expression had shorter overall survival time than those with high miR-145 expression (P < 0.001). When analyzed with a multivariate Cox regression model, miR-145 was identified as an independent prognostic factor for overall survival. Taken together, our results suggest that downregulation of miR-145 in cervical cancer is associated with aggressive progression and poor prognosis and that miR-145 may serve as a prognostic marker.
Sam68 (Src-associated in mitosis of 68 kDa) is a substrate for tyrosine kinase c-Src during mitosis. The nuclear protein level has been found to be associated with progression and prognosis in various human malignant tumors. The aim of this study is to investigate the clinical value of Sam68 in endometrial carcinoma (EC). Sam68 expression was confirmed by real-time PCR, Western blot, and immunofluorescent assay in primary normal endometrial epithelial cells, endometrial carcinoma cell lines, as well as seven pairs of EC and matched adjacent noncancerous endometrial tissues. Moreover, the protein level of Sam68 was evaluated by immunohistochemistry in a cohort of surgical specimens derived from 131 patients including primary endometrial carcinoma (n = 95), endometrial atypical hyperplasia (precancerous lesions, n = 26), and normal endometria (n = 10). In endometrial cancer cell lines, RNA interfering approach was employed to downregulate Sam68 expression to determine its role in proliferation. Clinicopathological relevance and prognostic associations were examined by statistical analyses. Compared with normal endometrial and endometrial atypical hyperplasia tissues, Sam68 significantly elevated in endometrial cancer samples (P < 0.01), which was negative or low in 37 cases (38.9 %) and high in 58 cases (61.1 %). The high expression of Sam68 was associated with histological grade (P < 0.001), FIGO stage (P = 0.039), and myometrial invasion (P = 0.002). Kaplan-Meier analysis demonstrated that overexpression of Sam68 correlated with shorter overall survival. It is confirmed by univariate and multivariate analysis (P < 0.001 and P = 0.048, respectively). Additionally, we found that Sam68 was highly expressed at both the transcriptional and translational levels in endometrial cancer cell lines (Ishikawa, HEC-1B, AN3CA, KLE, and RL95-2) and siRNA knockdown of Sam68 remarkably inhibited cellular proliferation in in vitro models. Sam68 may be useful prognostic marker for EC, and it plays an important role in promoting the cellular proliferation. Further investigation of Sam68 as a potential therapeutic target for EC patients could be of interest.
Endometrial carcinoma (EC) is one of the most common gynecological carcinomas. As previously described, ferroptosis was reported to exhibit a significant association with the development of malignant neoplasms. Nevertheless, there are few studies towards the association between the implication of ferroptosis-related genes (FRGs) and the prognostic status of patients with EC. Our study demonstrated that ferroptosis-related genes were evidently differently expressed in EC. Further analysis showed that SLC7A11, SAT1, CDKN1A, and TP5MC3 expression was linked to the low stage, grade of pTNM, and longer survival time. Bioinformatics analysis demonstrated that these ferroptosis-related regulators played a crucial role in EC by modulating multiple biological processes, such as cell cycle, citrate cycle (TCA cycle), metabolism-related pathways, ERK activation, p53 signaling pathway, cellular senescence, TAp63 pathway, and Notch signaling pathway. Of note, our results showed that ATP5MC3, CDKN1A, and SLC7A11 expression was dramatically positively related with the tumor mutational burden (TMB) score in EC. However, we did not observe a significant correlation between SAT1 and the TMB score in EC. These findings for the first time demonstrated that ferroptosis was displayed crucially in EC progression. We speculated that our findings offered novel targets and strategies for personalized treatment.
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