title: SIRT6 is upregulated and associated with cancer aggressiveness in papillary thyroid cancer via BRAF/ERK/Mcl‑1 pathway.
abstract: Sirtuin 6 (SIRT6) is a member of the SIRT family NAD+‑dependent deacetylases reported to function in controlling organism homeostasis, lifespan, and diseases. This study investigated the role of SIRT6 in papillary thyroid cancer (PTC). Data of 391 PTC patients was extracted from The Cancer Genome Atlas database to investigate the expression of SIRTs (SIRT1‑7) and their relationship with clinicopathological parameters. Additional 45 pairs of PTC tumor tissues and corresponding non‑tumor tissues were studied using microarray analysis for SIRT6 expression. Surgically resected, pathologically diagnosed tissues from 130 in‑house PTC patients were used for confirmation of SIRT6 expression. SIRT6 silenced K1 and TPC‑1 cells were generated to explore the influence of SIRT6 on cancer cell aggressiveness in vitro. SIRT6 mRNA and protein levels were upregulated in PTC tumor tissues and its overexpression was an independent biomarker for nodal metastasis (odds ratio=1.794, 95% confidence interval: 1.256‑1.920, p=0.012). SIRT6 expression was related to poor recurrence‑free survival, however, not significantly. Silencing SIRT6 downregulated PTC cell aggressiveness in vitro by suppressing ERK and Mcl‑1. In conclusion, these results suggest that SIRT6 enhances cell aggressiveness in PTC via BRAF/ERK/Mcl‑1 pathway, and thus may be a promising target in the treatment of the disease.
authors.affiliation: Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Qu
authors.affiliation: Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Jia-Qian
authors.initials: JQ
authors.lastname: Hu
authors.affiliation: Department of Radiology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Zhang
authors.affiliation: Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Sun
authors.affiliation: Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Rong-Liang
authors.initials: RL
authors.lastname: Shi
authors.affiliation: Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Qing-Hai
authors.initials: QH
authors.lastname: Ji
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002291:Carcinoma, Papillary; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics*; D009367:Neoplasm Staging; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D037761:Sirtuins / Q000096:biosynthesis / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C516592:SIRT6 protein, human; D037761:Sirtuins