Mechanism Of ACTL6A Regulating Cell Cycle Progression Of Cervical Cancer

Cervical cancer is the most common malignant tumor of female reproductive which seriously endangers the life and health of patients.Recently,although cervical cancer screening programs have been widely carried out,the incidence rate and mortality rate of cervical cancer is increasing steadily both in the world and in China.At present,the treatment strategies of cervical cancer include radical surgery,radiotherapy,chemotherapy and immunotherapy have been widely used,however,the curative effect for advanced diseases is still very limited.The identification of more reliable genetic,molecular and immunohistochemical markers can improve the survival of patients with cervical cancer.ACTL6A(BAF53A)is one of the important subunits of chromatin remodeling complex SWI/SNF.It maintains the regional structure of chromosome in mammalian cells and participates in the formation of np BAF complex,which mediates the expression of genes related to the division and proliferation of neural progenitor cells.Since ACTL6 A was first reported in CELL,its role in tumorigenesis and development has attracted more and more attention.In liver cancer,rhabdomyosarcoma,head and neck squamous cell carcinoma,colon cancer,breast cancer and lung cancer,ACTL6 A is not only associated with survival prognosis,but also is found to promote tumor cell proliferation,anchorage independent growth and drug resistance.In a previous study,we found that ACTL6 A is not only highly expressed in ovarian cancer,which is related to poor prognosis,but also mediates follicle stimulating hormone(FSH)-induced glycolysis by regulating PGK1.However,the expression of ACTL6 A in cervical cancer and its potential mechanism are not clear.In this study,we verified the high expression of ACTL6 A in cervical cancer by bioinformatics and immunohistochemistry.CCK-8,clone formation assay and nude mice tumorigenesis experiments showed that ACTL6 A could promote the proliferation of cervical cancer cells.At the same time,q RT-PCR and correlation analysis showed that ACTL6 A regulated the expression of differentiation related genes(S100P,S100A4,krt7 and TGM2)in cervical cancer cells.GSEA function enrichment analysis showed that the expression of ACTL6 A was related to cell cycle regulation.Flow cytometry verified that knockdown of ACTL6 A could increase the proportion of G1 phase and reduce the proportion of S phase of cervical cancer cells.Moreover,q RT-PCR and western blot confirmed that ACTL6 A regulated the expression of cell cycle related genes,including cyclin A2,MCM2 and Skp2.Further studies showed that ACTL6 A not only interacted with c-Myc and MAX,but also promoted the transcriptional activity of c-myc.Additionally,knockdown of c-myc not only inhibited the proliferation of cervical cancer cells stimulated by ACTL6 A,but also attenuated the cell cycle process induced by ACTL6 A.To sum up,in this subject,we explored the expression of ACTL6 A in cervical cancer and clarified the molecular mechanism of ACTL6 A regulating cell cycle and promoting cervical cancer cell proliferation through c-myc.This topic provides a theoretical basis for further revealing the mechanism of the occurrence and development of cervical cancer and exploring effective targeted treatment strategies.