The Promoting Effect Of LncRNA SLC7A11-AS1 On The Synthesis Of Unsaturated Fatty Acids In Pancreatic Cancer Cells

Pancreatic cancer is a highly malignant tumor of the digestive system.At present,gemcitabine is still the first-line treatment for pancreatic cancer,but long-term use of gemcitabine in patients has resulted in resistance.Lipid metabolic reprogramming is the most significant metabolic pathway associated with gemcitabine resistance adverse reactions.Long non-coding RNAs(lnc RNAs)play an important role in the genesis,development,formation of CSCs and drug resistance of tumors.In this paper,the expression microarray analysis of pancreatic cancer cell line PANC-1 sh-SLC7A11-AS1 and its negative control PANC-1 sh-Ctrl was performed,and it was found that the expression of genes related to lipid metabolism,such as SCD-1,ACLY and ACAT2,were down-regulated.The expression level of SCD-1was higher in PANC-1 background.SLC7A11-AS1 was silenced in pancreatic cancer drug-resistant cells PANC-1 and Bx PC-3-Gem,and the results showed downregulation of SCD-1,ACLY and ACAT2 genes,with the most obvious down-regulation of SCD-1.Oil red O assay of lipid synthesis in pancreatic cancer sensitive cell MIA-Pa Ca-2 showed that SLC7A11-AS1 promoted lipid synthesis.The following is the dry study of SLC7A11-AS1 and SCD-1.SLC7A11-AS1 and SCD-1 were highly expressed in pellet cells.After silencing SLC7A11-AS1,SCD-1 was overexpressed in PANC-1 and Bx PC-3,and the expression levels of CD133 and CD44 and cell pellet formation were detected.The results showed that after silencing SLC7A11-AS1,the expression of CD133 and CD44 and the pelleting ability of cells were decreased.CD133,CD44 expression and pellet-forming ability of cells were increased after overexpression of SCD-1.The silencing effect of SLC7A11-AS1 can be partially restored after the overexpression of SCD-1.The formation of unsaturated fatty acids by exogenous palmitic acid under the catalysis of SCD-1 promoted pancreatic cell dryness and the expression levels of CD133 and CD44.SLC7A11-AS1 affected the regulation of pancreatic cell dryness by lipid through the regulation of SCD-1.These results suggest that SLC7A11-AS1 regulates pancreatic tumor cell dryness through SCD-1.SCD-1 is highly expressed in pancreatic cancer patients,and SLC7A11-AS1 is positively correlated with the expression of SCD-1 in pancreatic cells.Finally,the mechanism of SLC7A11-AS1 regulating SCD-1 was studied.Silencing SLC7A11-AS1 in PANC-1 found that p65 expression was down-regulated,and p65 regulated the expression of SCD-1.These results suggest that SLC7A11-AS1 regulates SCD-1 expression through p65.In conclusion,this study reveals the role of SLC7A11-AS1 in the regulation of lipid metabolism,and provides a theoretical basis for the study on the mechanism of pancreatic cancer drug resistance.