ArticleInternational journal of clinical and experimental pathology2018
SIRT6 overexpression inhibits HIF1α expression and its impact on tumor angiogenesis in lung cancer.
Article in International journal of clinical and experimental pathology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 8 citations in OpenAlex.
- Emerging role of sirtuins in non‑small cell lung cancer (Review).Oncology reports · 2024Review
- Astragaloside IV restrains pyroptosis and fibrotic development of pulmonary artery smooth muscle cells to ameliorate pulmonary artery hypertension through the PHD2/HIF1α signaling pathway.BMC pulmonary medicine · 2023Article
- Bioinformatic Analysis of the Effect of theBioMed research international · 2022Article
- Is nuclear sirtuin SIRT6 a master regulator of immune function?American journal of physiology. Endocrinology and metabolism · 2021Review
- Emerging roles of SIRT6 in human diseases and its modulators.Medicinal research reviews · 2021Review
- Sirtuin 6 and metabolic genes interplay in Warburg effect in cancers.Journal of clinical biochemistry and nutrition · 2020Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
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Abstract
objectiveTo investigate the effect of silencing information regulator 6 (SIRT6) on HIF1α expression of cell line A549 in non-small cell lung cancer and on tumor angiogenesis in lung cancer.
methodsCell line A549 in the logarithmic growth phase was transfected with Ad-SIRT6 and Ad-null respectively. According to the study design, the cells were divided into control group, Ad-null group and Ad-SIRT6 group. The HIF1α and HIF2α mRNA expression in each group were detected by real-time quantitative PCR (qPCR). The level of prolyl hydroxylase (PHD) 1-3 after 48 h of Ad-SIRT6-transfected cell line A549 and the levels of VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 in the supernatants were determined by ELISA. The nude mice were injected subcutaneously with Ad-null or Ad-SIRT6 transfected cell line A549. The tumor volume was observed at 6, 12, 18, 24 and 30 d after inoculation, and the tumor mass was weighed at 30 d. Also, microvessel density (MVD) and the number of positive HIF1α and VEGF cells were detected by immunohistochemistry. The VEGF and HIF1α levels in tumor tissue were detected by ELISA and qPCR respectively.
resultsqPCR showed that the levels of HIF-1α mRNA, VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 in the supernatant were decreased, the level of PHD2 was increased (P<0.05), and the levels of HIF-2α mRNA, PHD1 and PHD3 did not change much (P>0.05) in the Ad-SIRT6 group as compared with those in the control group and Ad-null group. The tumor growth rate was decreased, and the tumor volume at 12-30 d after inoculation was less in the Ad-SIRT6 group than in the control group and Ad-null group (P<0.05); the tumor mass was also lower than that of control and Ad-null groups (P<0.05). Immunohistochemistry showed that MVD and the number of HIF-1α and VEGF positive cells were less in the Ad-SIRT6 group than in control and Ad-null groups (P<0.05); and HIF-1α and VEGF levels in tumor tissue were decreased in the Ad-SIRT6 group compared to the control and Ad-null groups (P<0.05). There were no significant differences in the above measurements between the control group and Ad-null group (P>0.05).
conclusionSIRT6 overexpression can inhibit HIF1α and VEGF expression, promoting PHD2 expression, which can inhibit angiogenesis and xenograft growth and may play a role in reducing HIF1α and VEGF expression.
Indexed as
Identifiers
31938419PMC6958067W3027841141What OpenQuestion holds
Registered trials
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