title: siRNA-mediated knockdown of hTDE2 retards cell cycle progression through transcriptional activation of p21.
abstract: Carcinogenesis is a very complex process involving a series of changes of tumor-related genes. Therefore, genes differentially expressed in tumors have received significant attention. Among them is the tumor differentially expressed (TDE) protein family, which shows no homologue to any other protein families and is unique to eukaryotes. The members of the TDE (also known as Serinc) family are highly conserved, showing approximately 30-80% homologue of their amino acid sequences. Previous reports have shown that both human and mice TDE/Serinc proteins are always upregulated in carcinomatous tissues. However, their precise physiological roles remain unclear. The human TDE2/Serinc1 gene was cloned by our laboratory during the screening for differentially expressed genes in hepatocarcinoma. In the present study, we knocked down the expression of TDE2 with specific siRNA fragments in two human hepatocarcinoma cell lines, and this caused cell cycle arrest at G2. Cell cycle progression is monitored and regulated by several factors. p21, the cdk inhibitor, is a key player and could be transcriptionally activated by many factors including sterol regulatory element-binding proteins (SREBPs). Previous research demonstrated that rat TDE2 could facilitate the cellular sphingolipids biosynthesis in both yeast and mammalian cells. Therefore, we further analyzed the effect of TDE2 knockdown on p21 and SREBP, and found that endogenous p21 expression was upregulated, as was that of SREBPs (-1a and 2). In conclusion, our preliminary results indicated that TDE2 may have an effect on tumor cell growth by influencing the expression of SREBP and p21.
authors.affiliation: The State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, P.R. China.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Ren
authors.affiliation: The State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, P.R. China.
authors.forename: Chen-Yi
authors.initials: CY
authors.lastname: Yang
authors.affiliation: The State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, P.R. China.
authors.forename: Xian-Mei
authors.initials: XM
authors.lastname: Yang
authors.affiliation: The State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, P.R. China.
authors.forename: Long
authors.initials: L
authors.lastname: Yu
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics* / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints; D055785:Gene Knockdown Techniques; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics*; D020218:Response Elements; D051779:Sterol Regulatory Element Binding Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D008565:Membrane Proteins; D034741:RNA, Small Interfering; C477932:SERINC1 protein, human; D051779:Sterol Regulatory Element Binding Proteins