Our data suggest that ovarian cancer contain small sub-population of side population cells which shares some characteristics of stem cells. The co-expression of ABC transporters and stem cells surface markers in SP cells may associate with resistance to chemotherapeutic agents, apoptosis and also supports a role for these cells in tumor recurrence, metastasis and invasion.
Objective
High mobility group box 3 (HMGB3) plays an important role in the development of various cancer. This study aims to explore whether HMGB3 regulates cervical cancer (CC) progression and elucidate the underlying mechanism.
Methods
HMGB3 expression in clinical patients' tumor samples were determined by real-time quantitative polymerase chain reaction (qRT-PCR) and western blot. HMGB3 overexpression/knockdown were used to investigate its function. Cell apoptosis and cycle were detected by Annexin V/PI staining and flow cytometry. In vivo tumor model was made by subcutaneous injection of HeLa cells transfected with shRNAs targeting HMGB3 (sh-HMGB31) into the flank area of nude mice. Western blot was used to detect the levels of β-catenin, c-Myc, and matrix metalloproteinase-7 (MMP-7) in Hela and CaSki cells transfected with sh-HMGB3 or shRNAs targeting β-catenin.
Results
Both messenger RNA and protein levels of HMGB3 were upregulated in CC tissues from patients. High expression level of HMGB3 had positive correlation with serosal invasion, lymph metastasis, and tumor sizes in CC patient. Functional experiments showed that HMGB3 could promote CC cell proliferation both in vitro and in vivo. The expression levels of c-Myc and MMP-7 were increased, resulting in regulating cell apoptosis, cell cycle, and activating Wnt/β-catenin pathway.
Conclusions
Our data indicated that HMGB3 may serve as an oncoprotein. It could be used as a potential prognostic marker and represent a promising therapeutic strategy for CC treatment.
IntroductionOvarian cancer (OVCA) is one of the most prevalent malignant tumors of the female reproductive system, and its diagnosis is typically accompanied by the production of ascites. Although liquid biopsy has been widely implemented recently, the diagnosis or prognosis of OVCA based on liquid biopsy remains the primary emphasis.MethodsIn this study, using proximity barcoding assay, a technique for analyzing the surface proteins on single extracellular vesicles (EVs). For validation, serum and ascites samples from patients with epithelial ovarian cancer (EOC) were collected, and their levels of CDCP1 was determined by enzyme-linked immunosorbent assay. Tissue chips were prepared to analyze the relationship between different expression levels of CDCP1 and the prognosis of ovarian cancer patients.ResultsWe discovered that the CUB domain-containing protein 1+ (CDCP1+) EVs subcluster was higher in the ascites of OVCA patients compared to benign ascites. At the same time, the level of CDCP1 was considerably elevated in the ascites of OVCA patients. The overall survival and disease-free survival of the group with high CDCP1 expression in EOC were significantly lower than those of the group with low expression. In addition, the receiver operating characteristic curve demonstrates that EVs-derived CDCP1 was a biomarker of early response in OVCA ascites.DiscussionOur findings identified a CDCP1+ EVs subcluster in the ascites of OVCA patients as a possible biomarker for EOC prevention.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.