Expression And Mechanism Of CRYAB In Cervical Cancer

Objective: Cervical cancer is one of the most common gynecological malignancies,posing a serious threat to women’s physical and mental health.China had 109,741 new cases and 59,060 deaths in 2020.At present,deaths from early cervical cancer are already rare,but in advanced or recurrent patients with high mortality rate.The etiology of cervical cancer is not completely clear,except the human papilloma virus is recognized,the molecular mechanism of cervical cancer is still in the stage of extensive exploration.At present,there are few targets that can be used in clinical diagnosis,treatment and prognosis evaluation of cervical cancer.α B-Crystallin(CRYAB)is a protein coding gene that plays an important role in the protection of cells from stress and in the prevention of protein aggregation as a molecular Heat shock protein.CRYAB can inhibit cell apoptosis and participate in cell cycle and cell proliferation regulation,which are closely related to tumorigenesis and development.It is known that CRYAB differentially expressed in lung cancer,gastric cancer,nasopharyngeal cancer,and bladder cancer and is involved in tumor regulation.Analysis of transcriptome sequencing results showed that CRYAB is a core protein in the protein-protein interaction network with low expression in cervical cancer.The purpose of this study is to investigate the expression and mechanism of CRYAB in cervical cancer,and to provide scientific theoretical support for the prevention and control of cervical cancer.Methods:(1)Analyze the expression of CRYAB in cervical carcer and pan-neoplastic tissues and to study the relationship between the differential expression of CRYAB and tumor survival.The m RNA and protein expression of CRYAB in human normal cervical epithelial cells,Hela cells and Si Ha cells were detected by RT-PCR and Western blot respectively.(2)Overexpression of CRYAB lentiviral vector was constructed and transfected into Hela and Siha cell lines to obtain stable overexpression cell lines,cell apoptosis,cell cycle,cell migration,invasiveness and cell viability were measured.(3)The overexpression of CRYAB in cervical cancer cell lines was sequenced by RNA sequencing,and the bioinformatics analysis was used to screen the important molecules and signal pathways related to the phenotype of CRYAB.Results:(1)CRYAB is low expression in cervical cancer,may act as a tumor suppressor gene in cervical cancer.There were differential expression of CRYAB in 25 kinds of tumors,including 17 with low expression and 8 with high expression.Low expression of CRYAB in ovarian,lung and stomach cancers predicts higher overall survival.(2)after overexpression of CRYAB,the activity of Siha cells decreased obviously,the activity of Hela cells did not change obviously,the apoptosis of Si Ha cells increased obviously,the apoptosis of Hela cells did not change obviously,the S phase of Hela and Siha cells decreased obviously;The invasiveness of SIHA cells decreased significantly,while the invasiveness of Hela cells did not change significantly.The migration ability of Hela and Si Ha cells decreased significantly.(3)there were 3695 differentially expressed genes after overexpression of CRYAB,among which 1858 genes were overexpressed and 1837 genes were underexpressed.The Gene Ontology(GO)analysis showed that the top 5 biological processes with the most differential genes were myeloid leukocyte mediated immunity,leukocyte degranulation,myeloid cell activation involved in immune response,neutrophil mediated immunity,granulocyte activation.These differentially expressed genes are mainly concentrated in Longevity regulating pathway,Fox O signaling pathway,Endocytosis,cell cycle and Cellular senescence and other pathways.Conclusions:(1)CRYAB is low expression in cervical cancer,may act as a tumor suppressor gene in cervical cancer.(2)CRYAB has the ability to inhibit cell activity,migration and invasion,and to promote apoptosis.CRYAB has the potential to be used as a diagnostic and therapeutic target for cervical cancer.(3)CRYAB may be involved in the regulation of cervical cancer through the longevity regulating pathway.