Effect Of LncRNA CRNDE On The Malignant Behavior Of Pancreatic Cancer Cells By Regulating Hippo Pathway In Acidic Environment

BACKGROUND: It has been proved that long non-coding RNA(lnc RNA)is a kind of novel gene expression regulator.Although lncRNA is not capable of encoding functional proteins,but it can regulate gene expression at various levels,such as epigenetics,transcriptional level and post-transcriptional modification.LncRNA plays a crucial role in the development of various types of tumors in human.Recently,studies have found that the acidic microenvironment can affect the occurrence and development of tumors by inducing the stability of cell chromosomes and regulating gene expression.The acidic microenvironment not only plays an important role in the occurrence and development of malignant transformation of human tumors,but also has a significant effect on the efficacy of oncology drug treatment.However,the mechanism of how the acidic microenvironment regulates lncRNA expression and its function in the development of pancreatic cancer is still unclear.RESEARCH PURSOSES: Based on previous studies,we found that lncRNA CRNDE is highly overexpressed in pancreatic cancer tissues and cells.So,this study was to investigate the effects of acidic environment on the expression of lncRNA CRNDE in pancreatic cancer.We also want to elucidate whether CRNDE can alter the malignant biological behaviors in pancreatic cancer cells under acidic environment by regulating Hippo signaling pathway.METHODS: Firstly,real-time quantitative PCR was used to detect the expression of lncRNA CRNDE in 20 pairs of pancreatic cancer tissues and adjacent normal tissues.Then,the siRNA interference plasmid of lncRNA CRNDE was transfected into pancreatic cancer cells.And the expression of Hippo pathway related genes in pancreatic cancer cells were studied.Next,western blot was performed to examine the expression of YAP and TAZ proteins in the Hippo pathway.Finally,CCK8,flow cytometry,Transwell and other in vitro experiments were conducted to detect the ability of proliferation,apoptosis and invasion of pancreatic cancer cells after interference with siRNA-CRNDE.RESULTS AND DISCUSSION: The results showed that the expression of lncRNA CRNDE in pancreatic cancer tissues was significantly higher than that in adjacent normal tissues(P<0.05).It was also found that CRNDE is overexpressed in pancreatic cancer cells when cultured with acidic environment.Pancreatic cancer cells which were effectively transfected with siRNA-CRNDE interference plasmid can significantly inhibit the activation of Hippo pathway and down-regulated the expression of oncogene YAP/TAZ.It was also performed that in the acidic environment,interference with lncRNA CRNDE gene expression can apparently inhibit pancreatic cancer cells’ ability of proliferation,promote apoptosis and reduce invasion ability in vitro.