Sirtuin 6 plays an oncogenic role and induces cell autophagy in esophageal cancer cells

Sirtuin 6, a member of sirtuin family, is generally regarded as a tumor suppressor as it participates in suppressing hypoxia-inducible factor 1α and MYC transcription activity by deacetylating H3K9 (histone H3 lysine 9) and H3K56 (histone H3 lysine) at promoters of target genes, leading to the aerob...

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Main Authors: Nan Huang, Zhiwei Liu, Jiabei Zhu, Zhongqi Cui, Yuguang Li, Yongchun Yu, Fenyong Sun, Qiuhui Pan, Qingyuan Yang
Format: Article
Language:English
Published: SAGE Publishing 2017-06-01
Series:Tumor Biology
Online Access:https://doi.org/10.1177/1010428317708532
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author Nan Huang
Zhiwei Liu
Jiabei Zhu
Zhongqi Cui
Yuguang Li
Yongchun Yu
Fenyong Sun
Qiuhui Pan
Qingyuan Yang
author_facet Nan Huang
Zhiwei Liu
Jiabei Zhu
Zhongqi Cui
Yuguang Li
Yongchun Yu
Fenyong Sun
Qiuhui Pan
Qingyuan Yang
author_sort Nan Huang
collection DOAJ
description Sirtuin 6, a member of sirtuin family, is generally regarded as a tumor suppressor as it participates in suppressing hypoxia-inducible factor 1α and MYC transcription activity by deacetylating H3K9 (histone H3 lysine 9) and H3K56 (histone H3 lysine) at promoters of target genes, leading to the aerobic glycolysis inhibition and cell growth suppression. However, its expression has recently been reported to be highly elevated in a series of tumors, including prostate cancer, breast cancer, and non–small cell lung cancer, indicating that sirtuin 6 plays dual roles in tumorigenicity in a cell/tumor type–specific manner. To our knowledge, the biological roles of sirtuin 6 in esophageal cancer cells have still been underestimated. In the study, data from quantitative reverse transcriptase polymerase chain reaction–based assays and immunohistochemical assays revealed that sirtuin 6 was remarkably overexpressed in esophageal squamous tumor tissues. Moreover, its upregulation was closely related with clinical features, such as gender, pathology, tumor–node–metastasis, and cell differentiation. Subsequently, the biological tests showed that it promoted cell proliferation and induced the expression of Bcl2, a key anti-apoptotic factor, in esophageal carcinoma cells. Moreover, using the ratio of LC3II/I, a widely recognized autophagy biomarker, we showed that it apparently induced cell autophagy, which was further confirmed by the autophagy flux assays. In addition, results from western blotting assays and immunoprecipitation assays displayed that sirtuin 6 specifically interacted with ULK1 and positively regulated its activity by inhibiting its upstream factor mammalian target of rapamycin activity. In summary, our studies shed insights into the crucial functions of sirtuin 6 in esophageal carcinoma cells and provide evidence supporting sirtuin 6–based personalized therapies in esophageal carcinoma cell patients.
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spelling doaj-art-7acd2859d2b9423fa93607d2a4e7cce92025-08-20T03:14:58ZengSAGE PublishingTumor Biology1423-03802017-06-013910.1177/1010428317708532Sirtuin 6 plays an oncogenic role and induces cell autophagy in esophageal cancer cellsNan Huang0Zhiwei Liu1Jiabei Zhu2Zhongqi Cui3Yuguang Li4Yongchun Yu5Fenyong Sun6Qiuhui Pan7Qingyuan Yang8Department of Clinical Laboratory Medicine, Shanghai Tenth People’s Hospital of Tongji University, Shanghai, ChinaDepartment of Laboratory, Central Hospital of Panyu District, Guangzhou, ChinaDepartment of Laboratory Medicine, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Clinical Laboratory Medicine, Shanghai Tenth People’s Hospital of Tongji University, Shanghai, ChinaDepartment of Laboratory, Central Hospital of Panyu District, Guangzhou, ChinaCentral Laboratory, Shanghai Municipal Hospital of Traditional Chinese Medicine Affiliated With Shanghai TCM University, Shanghai, ChinaDepartment of Clinical Laboratory Medicine, Shanghai Tenth People’s Hospital of Tongji University, Shanghai, ChinaDepartment of Laboratory Medicine, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Clinical Laboratory Medicine, Shanghai Tenth People’s Hospital of Tongji University, Shanghai, ChinaSirtuin 6, a member of sirtuin family, is generally regarded as a tumor suppressor as it participates in suppressing hypoxia-inducible factor 1α and MYC transcription activity by deacetylating H3K9 (histone H3 lysine 9) and H3K56 (histone H3 lysine) at promoters of target genes, leading to the aerobic glycolysis inhibition and cell growth suppression. However, its expression has recently been reported to be highly elevated in a series of tumors, including prostate cancer, breast cancer, and non–small cell lung cancer, indicating that sirtuin 6 plays dual roles in tumorigenicity in a cell/tumor type–specific manner. To our knowledge, the biological roles of sirtuin 6 in esophageal cancer cells have still been underestimated. In the study, data from quantitative reverse transcriptase polymerase chain reaction–based assays and immunohistochemical assays revealed that sirtuin 6 was remarkably overexpressed in esophageal squamous tumor tissues. Moreover, its upregulation was closely related with clinical features, such as gender, pathology, tumor–node–metastasis, and cell differentiation. Subsequently, the biological tests showed that it promoted cell proliferation and induced the expression of Bcl2, a key anti-apoptotic factor, in esophageal carcinoma cells. Moreover, using the ratio of LC3II/I, a widely recognized autophagy biomarker, we showed that it apparently induced cell autophagy, which was further confirmed by the autophagy flux assays. In addition, results from western blotting assays and immunoprecipitation assays displayed that sirtuin 6 specifically interacted with ULK1 and positively regulated its activity by inhibiting its upstream factor mammalian target of rapamycin activity. In summary, our studies shed insights into the crucial functions of sirtuin 6 in esophageal carcinoma cells and provide evidence supporting sirtuin 6–based personalized therapies in esophageal carcinoma cell patients.https://doi.org/10.1177/1010428317708532
spellingShingle Nan Huang
Zhiwei Liu
Jiabei Zhu
Zhongqi Cui
Yuguang Li
Yongchun Yu
Fenyong Sun
Qiuhui Pan
Qingyuan Yang
Sirtuin 6 plays an oncogenic role and induces cell autophagy in esophageal cancer cells
Tumor Biology
title Sirtuin 6 plays an oncogenic role and induces cell autophagy in esophageal cancer cells
title_full Sirtuin 6 plays an oncogenic role and induces cell autophagy in esophageal cancer cells
title_fullStr Sirtuin 6 plays an oncogenic role and induces cell autophagy in esophageal cancer cells
title_full_unstemmed Sirtuin 6 plays an oncogenic role and induces cell autophagy in esophageal cancer cells
title_short Sirtuin 6 plays an oncogenic role and induces cell autophagy in esophageal cancer cells
title_sort sirtuin 6 plays an oncogenic role and induces cell autophagy in esophageal cancer cells
url https://doi.org/10.1177/1010428317708532
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