title: Clinical and therapeutic significance of sirtuin-4 expression in colorectal cancer.
abstract: Several members of the sirtuin family (SIRT1-7), which are a highly conserved family of NAD+-dependent enzymes, play an important role in tumor formation. Recent studies indicate that SIRT4 acts as a tumor suppressor by regulating glutamine metabolism. In the present study, we investigated the expression and activity of SIRT4 in colorectal cancer. Using a tissue microarray of 89 colorectal cancer cases, we found that SIRT4 was significantly downregulated in colorectal cancer tissues compared with that noted in the corresponding normal tissue (P<0.001). Lower SIRT4 levels were associated with worse pathological differentiation (P=0.031) and poorer post-operative overall survival rate (P=0.041). We found that SIRT4 overexpression inhibited the proliferation of colorectal cancer cells in vitro and in vivo. SIRT4 inhibited the glutamine metabolism of colorectal cancer cells and synergistically with glycolysis inhibitors induced cell death. SIRT4 also increased the sensitivity of colorectal cancer cells to chemotherapeutic drug 5-fluorouracil by inhibiting the cell cycle. Together, these results highlight the prognostic value of SIRT4 in colorectal cancer and the potential application of SIRT4 in colorectal cancer treatment.
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Guoyu
authors.initials: G
authors.lastname: Huang
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of General Surgery, First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, P.R. China.
authors.forename: Fudong
authors.initials: F
authors.lastname: Yu
authors.affiliation: Department of General Surgery, First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, P.R. China.
authors.forename: Xisheng
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of General Surgery, First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, P.R. China.
authors.forename: Chenwei
authors.initials: C
authors.lastname: Yuan
authors.affiliation: Department of General Surgery, First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, P.R. China.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of General Surgery, First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, P.R. China.
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Peng
mesh_terms: D000368:Aged; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D015870:Gene Expression; D005973:Glutamine / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D053208:Kaplan-Meier Estimate; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D015999:Multivariate Analysis; D009368:Neoplasm Transplantation; D011379:Prognosis; D016016:Proportional Hazards Models; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000964:Antimetabolites, Antineoplastic; D024101:Mitochondrial Proteins; D005973:Glutamine; C525357:SIRT4 protein, human; D037761:Sirtuins; D005472:Fluorouracil