The CircRNF144B/miR342-3p/FBXL11 Signaling Axis Promotes Ovarian Cancer Proliferation,invasion And Metastasis By Inhibiting Autophagy Through Ubiquitination And Degradation Of BECN1

Ovarian cancer(OC)is one of the common malignant tumors in women with high morbidity and mortality.Therefore,revealing the molecular mechanism of the occurrence and development of ovarian cancer(OC)is also very important to improve the survival rate and quality of life of ovarian cancer patients.important.Circular RNAs(circ RNAs)are a new class of non-coding RNAs without 5’-cap and 3’-poly(A)tails,which form circular structures through covalent bonds.The biological functions of circ RNAs have been extensively explored in a range of diseases,including autoimmune diseases,diabetes,and cancer.Previous studies have shown that circ RNAs can form sponges with mi RNAs and inhibit mi RNAs-induced degradation of mi RNA-target genes.Autophagy is widespread in eukaryotic cells in physiological or pathological states.Autophagy not only maintains intracellular homeostasis,but also provides nutrients for cell survival by breaking down damaged organelles and proteins,and plays a key role in the occurrence and development of ovarian cancer(OC).Previous studies have shown that circular RNAs(circ RNAs)have the potential to be involved in regulating autophagy and ovarian cancer(OC)progression.However,little is known about autophagy-related circ RNAs involved in ovarian cancer(OC)progression so far.In this study,we employed bioinformatics methods,RNA-sequencing and q RTPCR to detect the expression of circ RNF144 B in ovarian cancer(OC)tissues and cell lines and its correlation with patient prognosis.Cell function experiments and subcutaneous tumorigenesis experiments in nude mice were used to deter mine the role of circ RNF144 B in ovarian cancer(OC),while western blotting and confocal microscopy were used to deter mine its effect on autophagy.A dual-luciferase reporter assay,immunoprecipitation,and ubiquitination assay were combined to deter mine the molecular mechanism of circ RNF144 B in the process of autophagy and ovarian cancer(OC)progression.We found that circRNF144 B was increased in ovarian cancer(OC)tissues with low levels of autophagy,and high expression of circ RNF144 B was positively associated with poor prognosis.circ RNF144 B is mainly located in the cytoplasm,and silencing circ RNF144 B inhibited the proliferation and migration of ovarian cancer(OC)cells and increased autophagy;overexpression of circ RNF144 B induced the reverse effect.Mechanistically,circRNF144 B acts as a sponge for miR-342-3p and inhibits mi R-342-3p-mediated degradation of lysine demethylase 2A(FBXL11)m RNA,resulting in increased FBXL11 protein levels;mi R-342-Overexpression of3 p and silencing of FBXL11 can feedback inhibit circ RNF144 B to exert biological effects.In addition,FBXL11 can also bind to the autophagy key regulatory protein complex BECN1,increase its ubiquitination level and promote protein degradation,thereby inhibiting autophagy.We subsequently also found that Beclin1 overexpression and rapamycin inhibited circ RNF144B-regulated acceleration of ovarian cancer(OC)cell proliferation and migration via activation of autophagy.Taken together,circRNF144 B increases FBXL11 expression by sponging mi R-342-3p,and elevated FBXL11 promotes BECN1 ubiquitination and protein degradation,thereby inhibiting autophagic flux and promoting ovarian cancer(OC)progression.Therefore,we believe that circ RNF144 B may be an effective target and a new biological marker to promote ovarian cancer(OC)treatment,which is helpful for the early diagnosis and later treatment of ovarian cancer in women.