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The mechanism of BRCC3/NLRP3 in promoting the transformation of endometriosis to endometriosis-associated ovarian carcinoma
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Abstract:
Objective: To investigate the role of NOD-like receptor protein 3 (NLRP3) inflammatory vesicle activation in the progression of endometriosis (EMT) to endometriosis-associated ovarian cancer (EAOC) and the mechanism. Methods: EOAC tissues (n=15), EMT tissues (n=15), and normal endometrium tissues (CON, n=15) resected from patients during April 2018 and June 2019, as well as the clinical data of patients, were collected from the Shanghai Changning Maternity and Infant Health Hospital. Expression of NLRP3, BRCA1/BRCA2 containing complex subunit 3 (BRCC3), caspase-1 and IL-1β in the tissues of each group was detected by immunohistochemistry and WB methods. BRCC3 overexpression plasmids and si-BRCC3 plasmids were constructed and transfected into EMT CRL-7566 cells. The expression level of BRCC3 protein in the transfected cells was detected by WB method. The changes in cell proliferation, apoptosis, migration and invasion of transfected cells were detected by MTT method, flow cytometry and Transwell test, respectively. The BRCC3-overexpressing cells were further interfered with NLRP3. The expression levels of BRCC3 and NLRP3 proteins after the interference were detected by WB method, and the changes in cell proliferation, apoptosis, migration and invasion after interference were also detected. Results: The expression levels of NLRP3, caspase-1, IL-1β and BRCC3 in EAOC and EMT tissues were higher than those in CON group (all P<0.01), and there was a positive correlation between the expression of NLRP3 and BRCC3 in EAOC tissues (r=0.65, P<0.01). Overexpression of BRCC3 significantly promoted cell proliferation, migration and invasion and inhibited cell apoptosis in CRL-7566 cells (all P<0.01); While knockdown of BRCC3 had the opposite effects (all P<0.01). Over-expression of BRCC3 increased the expression level of NLRP3 (P<0.01), while interference with BRCC3 inhibited the expression of NLRP3 (P<0.01). Interference with NLRP3 partially attenuated the inhibition on cell apoptosis (P<0.01) and promotion on cell migration (P<0.05) and invasion (P<0.01) brought by BRCC3 overexpression. Conclusion: Both NLRP3 and BRCC3 are highly expressed in EAOC and EMT tissues. Over-expression of BRCC3 can promote the proliferation, migration and invasion but inhibit apoptosis of CRL-7566 cells. BRCC3/NLRP3 is a potential predictivemarker and treatment target for the transformation of EMT to EAOC.
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