Downregulation of <i>SIRT6</i> is associated with poor prognosis in patients with non-small cell lung cancer

Zhu, Bojin; Yan, Yongjin; Shao, Boyun; Tian, Luwen; Zhou, Weihua

doi:10.1177/0300060517750298

Cited by 17 publications

(9 citation statements)

References 32 publications

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“…The expression of SIRT6 is down-regulated in colon cancer, hepatocellular carcinoma, and head and neck squamous cell carcinoma [17]. Down-regulation of SIRT6 expression is associated with higher cancer staging and grades, as well as poor survival rates in cancer patients [18]. In contrast, SIRT6 expression is up-regulated in patients with prostate cancers, which is related to chemoresistance and poor prognosis in patients with cancer [19].…”

Section: Discussionmentioning

confidence: 99%

LncRNA HMMR-AS1 promotes proliferation and metastasis of lung adenocarcinoma by regulating MiR-138/sirt6 axis

Cai

Sheng

Chen

et al. 2019

Aging

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Purpose: Long noncoding RNAs (lncRNA) play critical roles in cancer development. In this study, we aimed to explore the function and possible molecular mechanism of HMMR-AS1 involved in lung adenocarcinoma (LUAD). Experimental Design: Firstly, we analyzed HMMR-AS1 expression in LUAD tissues with the sequencing data from The Cancer Genome Atlas (TCGA). Next, we evaluated the effects of HMMR-AS1 on LUAD cell proliferation and apoptosis, and its regulation of miR-138 by acting as a ceRNA. The animal model was used to support the in vitro experimental findings. Results: HMMR-AS1 expression was significantly upregulated in LUAD tissues and was associated with larger tumor diameter, advanced TNM stage, lymph node metastasis, and shorter survival. Knockdown of HMMR-AS1 induced apoptosis and growth arrest in vitro and inhibited tumorigenesis in mouse xenografts. Mechanistically, HMMR-AS1 functioned as a ceRNA of miR-138, thereby leading to repression of its endogenous target sirt6. Moreover, knockdown of HMMR-AS1 dramatically inhibited tumor growth and metastasis of LUAD in vivo . Conclusions: Taken together, HMMR-AS1 is significantly over-expressed in LUAD, and HMMR-AS1–miR-138–sirt6 axis play a critical role in LUAD tumorigenesis. Our findings highlight an oncogenic role of HMMR-AS1 in LUAD.

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Section: Discussionmentioning

confidence: 99%

LncRNA HMMR-AS1 promotes proliferation and metastasis of lung adenocarcinoma by regulating MiR-138/sirt6 axis

Cai

Sheng

Chen

et al. 2019

Aging

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“…These may be due to the differences of geography and cell lines in the selected samples of the studies. Some reports showed that SIRT6 was down‐regulated in NSCLC cells, 13 while some represented that SIRT6 was up‐regulated in NSCLC tissues and overexpression of SIRT6 was related to the poor prognosis of NSCLC 26 …”

Section: Discussionmentioning

confidence: 99%

“…Besides, Wang et al 12 discovered that overexpression of SIRT6 is able to inhibit the expression of HIF1α and VEGF, thereby restraining angiogenesis of lung cancer tumor. And Zhu et al 13 found that down‐regulation of SIRT6 expression is related to the poor prognosis of NSCLC, implying that SIRT6 has functions of controlling lung cancer development. Furthermore, it showed that overexpression of SIRT6 attenuates radioactive pneumonitis and lung injury 14 .…”

Section: Introductionmentioning

confidence: 99%

SIRT6 through PI3K/Akt/mTOR signaling pathway to enhance radiosensitivity of non‐Small cell lung cancer and inhibit tumor progression

et al. 2021

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To explore the effect and mechanism of SIRT6 on radiosensitivity and tumor progression of non‐small cell lung cancer (NSCLC). qRT‐PCR was performed to detect the expressions of SIRT6 in tumor tissues, adjacent normal tissues and NSCLC cell lines of patients with advanced NSCLC before and after radiotherapy. After overexpression or interference with SIRT6 expression in NSCLC cells, the cells were routinely cultured or transfected for 48 h followed by 4 Gy radiation for 24 h. Then, check the cell proliferation, migration, apoptosis and cell cycle by MTT, wound healing assay and flow cytometry, while detect the expression of PI3K/Akt/mTOR signaling pathway‐related proteins by Western blot. In addition, the effect of SIRT6 expression on NSCLC tumor growth was analyzed by xenograft tumor assay. SIRT6 showed a low expression in NSCLC tumor tissues and cell lines, while SIRT6 was significantly increased in NSCLC tissues after radiation treatment. Overexpression of SIRT6 in A549 and NCI‐H23 cells inhibited cell proliferation viability, migration ability and promoted apoptosis. By comparison, after radiation treatment, NSCLC cells with high SIRT6 expression had lower ability of proliferation and migration and higher apoptosis rate. Overexpression of SIRT6 evidently down‐regulated the activity of PI3K/Akt/mTOR signaling pathway in NSCLC cells before and after radiation. In addition, H2009 cells exhibited opposite cellular functions after interference with SIRT6 expression. In vivo experiments showed that overexpression of SIRT6 promoted the inhibitory effect of radiation on the growth of NSCLC xenograft tumors in nude mice. SIRT6 can promote the radiosensitivity of NSCLC and inhibit the development of tumor by down‐regulating the activity of PI3K/Akt/mTOR signaling pathway.

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“…Elaborating of the relationship between SIRT6 and NSCLC makes great sense for discovering a new biomarker for tumor targeting therapy 130 . Both the mRNA and protein SIRT6 levels were found downregulated in NSCLC tissue versus noncancerous tissue, and high expressions of SIRT6 appear to be favorable prognostic factors, indicating a tumor suppressor role of SIRT6 in NSCLC 87,131,132 . SIRT6 was firstly shown to suppress cell proliferation through downregulating the expression of oncogene Twist1 in NSCLC 87 .…”

Section: Human Diseasesmentioning

confidence: 99%

Emerging roles of SIRT6 in human diseases and its modulators

Liu

Chen

Liu

et al. 2020

Medicinal Research Reviews

103

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The biological functions of sirtuin 6 (SIRT6; e.g., deacetylation, defatty‐acylation, and mono‐ADP‐ribosylation) play a pivotal role in regulating lifespan and several fundamental processes controlling aging such as DNA repair, gene expression, and telomeric maintenance. Over the past decades, the aberration of SIRT6 has been extensively observed in diverse life‐threatening human diseases. In this comprehensive review, we summarize the critical roles of SIRT6 in the onset and progression of human diseases including cancer, inflammation, diabetes, steatohepatitis, arthritis, cardiovascular diseases, neurodegenerative diseases, viral infections, renal and corneal injuries, as well as the elucidation of the related signaling pathways. Moreover, we discuss the advances in the development of small molecule SIRT6 modulators including activators and inhibitors as well as their pharmacological profiles toward potential therapeutics for SIRT6‐mediated diseases.

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Downregulation of SIRT6 is associated with poor prognosis in patients with non-small cell lung cancer

Cited by 17 publications

References 32 publications

LncRNA HMMR-AS1 promotes proliferation and metastasis of lung adenocarcinoma by regulating MiR-138/sirt6 axis

LncRNA HMMR-AS1 promotes proliferation and metastasis of lung adenocarcinoma by regulating MiR-138/sirt6 axis

SIRT6 through PI3K/Akt/mTOR signaling pathway to enhance radiosensitivity of non‐Small cell lung cancer and inhibit tumor progression

Emerging roles of SIRT6 in human diseases and its modulators

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