The Feasibility Study Of Small G Proteins ARL8A And ARL8B As Anti-tumor Targets

ARL8A(ADP-ribosylation factor like protein 8A;also named ARL10C or Gie2)and ARL8B(ADP-ribosylation factor like protein 8B;also named ARL10B or Giel)are small G proteins that regulate the autophagy level of cells by controlling lysosomal migration and autophagosomes formation.The amino acid sequence similarity between the two proteins is over 91%.Both ARL8A and ARL8B are widely expressed in various organs of the human body and other mammals.There are certain evidence that both ARL8A and ARL8B are expressed in tumor cells,such as HeLa cell line.There are also cases where ARL8A is rarely expressed but ARL8B is predominantly expressed,such as prostate cancer cell line PPC1,which can be thought of as ARL8B-expressing tumor cells individually.In vitro and vivo experiments have convincingly proved that inhibiting ARL8B expression can significantly inhibit tumor growth in prostate cancer cells,so ARL8B is a target of anti-prostate cancer drugs.Based on the existing research results,it can be considered that the tumor cells with ARL8A predominantly expressed are likely to exist.Finding such cells is a prerequisite for studying the function of ARL8A.So far,there is no published research on the structure and function of ARL8A.Therefore,this study aims to look for ARL8A predominantly expressed tumor cells and study the function of ARL8A to confirm whether it was also an anti-tumor drugs target.In this paper,we report ARL8A or ARL8B predominantly expressed tumor cells and their results as targets for anti-tumor drugs.In the first chapter,we report the relative expression levels of ARL8A and ARL8B mRNA in some tumor cells using qRT-PCR.We firstly discover ARL8A advantage expression but ARL8B little expression in neuroblastoma cell SH-SY5Y.We also find that gastric cancer cell MGC-803 is ARL8B individual expression cell.The second chapter report the results of the study on the changes of cell viability and the mechanism of ARL8A in SH-SY5Y by ARL8A overexpression or knockdown.In the third chapter,we report the results of the study on gastric cancer cell MGC-803 that promotes cell death and its mechanism by knocking down ARL8B using RNA interference.In this study,we find that knocking down ARL8A or ARL8B expression levels can induce the increase of autophagy,and the autophagic level is particularly enhanced in ARL8A predominantly expressed or ARL8B predominantly expressed tumor cells.For cells that expressing both ARL8A and ARL8B,reducing the expression of only one of them does not result in significant death rate,probably because one protein will offset the decrease expression of another protein.Therefore,ARL8A can be identified as a potential new drug target for anti-neuroblastoma and ARL8B can also serve as a potential drug target for gastric low differentiation myxoid adenocarcinoma.