MGLL Inhibits The Growth Of Hepatocellular Carcinoma By Regulating The Expression Of KLF4

Background:Hepatocellular carcinoma(HCC)is one of the most lethal human cancers worldwide.HCC is widespread in Southeast Asia and sub-Sahara Africa and is related with a variety of risk factors,such as infection by HBV or HCV,chronic alcohol abuse,environmental factor and nonalcoholic fatty liver disease.HCC is a common cancer with 6,000,000 new cases diagnosed annually.Several genes having been found to play an important part in HCC development.However,the exact mechanisms of the development and progression of HCC remain unclear.Monoacylglycerol lipase(MGLL)as lipolytic enzymes of lipid metabolism,which can be decomposed triacylglycerol(TAG)into the free-fatty acid(FFA).It also plays a pivotal role in regulating endocannabinoid signaling in the nervous system and some other tissues,which breakdown 2-arachidonoylglycerol(2-AG).Endocannabinoids are lipid molecules that regulate a diverse set of physiological processes including pain,cognition,appetite,and emotional states,and their levels and functions are tightly modulating by enzymatic biosynthesis and degradation In 2011,Nomura found that MGLL plays a tumorigenic role in prostate cancer.Later,the function of MGLL in cancer was studied.KLF4 is one of the important factors in induced pluripotent stem cell(i PSC)technology.It regulates genes related to cell cycle regulation and epithelium differentiation.It acts as a tumor suppressor in colon,lung cancer and and HCC,and it functions as an oncogene in malignant tumors like B non-Hodgkin lymphomaStudies show that microenvironment plays an important role in the development of malignant tumors,however,the mechanisms underlying remain unclear.Metabolism is an essential feature of organisms.It becomes more significant in cancer research,especially the lipid metabolism.Recently,studies indicate that some enzymes related with metabolism can act as oncogenes or tumor suppressor genes involved in the development of tumor.MGLL is a lipolytic enzymes of lipid metabolism,additionally MGLL acts as a part of a gene expression signature that contributes to tumourigenesis.However,little is known about its regulation and function in HCC.Objectives:1.Clarify the expression of MGLL in HCC cell lines and tissues.2.Verify the molecular mechanisms of MGLL regulating the development of HCC.3.Reveal the function of MGLL as the tumor suppressor.Methods:1.Immunohistochemical staining analysis of HCC microarray.2.Construct plasmids of the knockdown or overexpression MGLL or KLF4.3.Construct stable cell lines by lentivirus package and study the functions of MGLL in HCC.Results:1.MGLL has low expression in HCC tissues and cells,and plays a role in HCC as tumor suppressor.2.Overexpression of MGLL inhibits the growth of HCC cells,knockdown MGLL promotes the growth of HCC cells.3.The lack of MGLL contributes to the migration of HCC cells.4.MGLL regulates the expression of KLF4 to inflect the growth of HCC cells.