title: Identification of natural splice variants of SAMHD1 in virus-infected HCC.
abstract: It has been previously shown that the sterile alpha motif domain and HD domain-containing protein 1 (SAMHD1) can act as a retroviral restriction factor by inhibiting HIV‑1 infection, but whether it has any roles in cancer is still unclear. In the present study, we identified several SAMHD1 splice variants naturally occurring in liver cancer and investigated their roles in regulating drug susceptibility. SAMHD1 variants were identified by sequencing. RT-PCR and western blot analysis were performed to verify the expression level of the polymorphisms. Cell cycle analysis was carried out using flow cytometry, and data were analyzed using Multicycle software. Several deletions of SAMHD1 were identified in both the patients and the healthy controls with no significant difference in respective frequencies, while an insertion in the exon4 occurred at a higher frequency in HBV- and HCV-infected patients (36.4 and 30%, respectively) when compared to the control groups. Following cisplatin treatment and cell cycle analysis, SAMHD1 variants showed different activities in increasing the susceptibility to chemotherapy drugs. The insertion of exon4 correlated with the occurrence of virus infection in the HCC patients. In conclusion, analysis of the different activities of SAMHD1 splice variants in regulating drug sensitivity implied that the exon4 insertion might act as an indicator of the occurrence of liver cancer.
authors: Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors: Yunpeng
authors: Y
authors: Shi
authors: Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors: Guoyue
authors: G
authors: Lv
authors: Department of Endocrinology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors: Zhe
authors: Z
authors: Chu
authors: Department of Endocrinology, The Fourth Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors: Liling
authors: L
authors: Piao
authors: Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors: Xingkai
authors: X
authors: Liu
authors: Hospital Management Section of Jilin University, Changchun, Jilin 130021, P.R. China.
authors: Tuo
authors: T
authors: Wang
authors: Key Laboratory of Zoonosis Research, Ministry of Education, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors: Yanfang
authors: Y
authors: Jiang
authors: Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors: Ping
authors: P
authors: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000235:genetics; D020022:Genetic Predisposition to Disease; D056945:Hep G2 Cells; D016174:Hepacivirus / Q000235:genetics; D006509:Hepatitis B / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics; D006526:Hepatitis C / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D020033:Protein Isoforms / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*; D000076106:SAM Domain and HD Domain-Containing Protein 1
chemical_list: D000970:Antineoplastic Agents; D020033:Protein Isoforms; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020559:Monomeric GTP-Binding Proteins; D002945:Cisplatin