The Influence Of ACTL6A In The Malignant Biological Behavior Of Pancreatic Carcinoma

Objective Actin like 6A(ACTL6A)is an essential component of the adenosine triphosphate(ATP)-dependent SWI/SNF-like BRG1/BRM-associated factor complex.Overexpression of ACTL6A promotes epithelial-mesenchymal transition(EMT)and has been shown to promote tumorigenesis and progression through EMT.Previous studies have shown that ACTL6A is associated with the development of hepatocellular carcinoma,colon cancer and other tumors.However,there are few reports on ACTL6A in pancreatic carcinoma(PC).This study investigates the expression of the ACTL6A gene in PC tissues.To investigate the relationship between ACTL6A gene expression levels and clinicopathological features as well as the impact of expression levels on prognosis To explore the effects of ACTL6A overexpression and silencing on the biological functions of PC SW1990 cells.To predict the possible signaling pathways regulated by ACTL6A in PC with bioinformatics.Methods The mRNA expression differences of ACTL6A in pancreatic and normal pancreatic tissues were analyzed by public databases and bioinformatics methods.The clinical information of PC patients in the TCGA database was used to analyze the differential expression of ACTL6A mRNA in PC tissues.The effect of ACTL6A mRNA on PC patients’ clinicopathological characteristics and the prognosis was also explored.Immunohistochemical staining experiments were performed using clinically collected pancreatic cancer case specimens.We also analyzed the effect of ACTL6A expression level on the clinicopathological characteristics and prognosis of pancreatic cancer patients.The effects of overexpressing and silencing of ACTL6A gene on biological functions such as proliferation,apoptosis,invasion and migration of PC SW1990 cells were analyzed.Finally,gene set enrichment analysis predicted the possible signaling pathways regulated by ACTL6A in PC.Results The expression level of ACTL6A gene were higher in PC tissues compared with normal pancreatic tissues.The expression level of ACTL6A was related to the pathological grade and tumor invasion depth of PC.Multivariate Cox analysis showed that lymph node metastasis and expression level of ACTL6A mRNA were independent risk factor for the prognosis of PC patients.The median survival time of PC patients in the high ACTL6A mRNA expression group was lower than that of patients in the low expression group.Clinical specimen data showed that ACTL6A was highly expressed in pancreatic cancer and its high expression correlated with malignant clinicopathological features of pancreatic cancer and affected the prognosis of pancreatic cancer patients.Overexpression of ACTL6A promoted the ability of proliferation,migration,and invasion in SW1990 cells and inhibited cell apoptosis.The opposite result is obtained after silencing ACTL6A.GSEA results showed that the group with high expression of ACTL6A mRNA was up-regulated in cell cycle,nucleotide excision repair,base excision repair,DNA replication,pathways in CANCER,NOTCH signaling pathway and other related gene sets.Conclusion The expression level of ACTL6A in PC is high,which is related to many malignant phenotypes.Patients with high expression of ACTL6A have worse prognosis,and the expression level of ACTL6 A was an independent risk factor for prognosis of PC patients.Overexpression of ACTL6A can promote the proliferation,metastasis and invasion ability of SW1990 cells and inhibit their apoptosis in vitro.In conclusion,ACTL6A is expected to be a new prognostic indicator and therapeutic target for PC.