SIRT6 is upregulated and associated with cancer aggressiveness in papillary thyroid cancer via BRAF/ERK/Mcl-1 pathway

Ning Qu, Jia Qian Hu, Liang Liu, Ting Ting Zhang, Guo Hua Sun, Rong Liangand Shi, Qing Hai Ji

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1683-1692
Number of pages10
JournalInternational journal of oncology
Volume50
Issue number5
DOIs
StatePublished - May 2017

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Neoplasms
Atlases
Microarray Analysis
Papillary Thyroid cancer
NAD
Homeostasis
Down-Regulation
Biomarkers
Odds Ratio
Genome
Databases
Confidence Intervals
Neoplasm Metastasis
Recurrence
Messenger RNA
Survival
Proteins
In Vitro Techniques
Therapeutics

Keywords

  • BRAF
  • ERK
  • Mcl-1
  • Papillary thyroid cancer
  • SIRT6

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

SIRT6 is upregulated and associated with cancer aggressiveness in papillary thyroid cancer via BRAF/ERK/Mcl-1 pathway. / Qu, Ning; Hu, Jia Qian; Liu, Liang; Zhang, Ting Ting; Sun, Guo Hua; Shi, Rong Liangand; Ji, Qing Hai.

In: International journal of oncology, Vol. 50, No. 5, 05.2017, p. 1683-1692.

Research output: Contribution to journalArticle

Qu, Ning ; Hu, Jia Qian ; Liu, Liang ; Zhang, Ting Ting ; Sun, Guo Hua ; Shi, Rong Liangand ; Ji, Qing Hai. / SIRT6 is upregulated and associated with cancer aggressiveness in papillary thyroid cancer via BRAF/ERK/Mcl-1 pathway. In: International journal of oncology. 2017 ; Vol. 50, No. 5. pp. 1683-1692.
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