Pro-Proliferative Function of Mitochondrial Sirtuin Deacetylase SIRT3 in Human Melanoma

George, Jasmine; Nihal, Minakshi; Singh, Chandra K.; Zhong, Weixiong; Liu, Xiaoqi; Ahmad, Nihal

doi:10.1016/j.jid.2015.12.026

Cited by 69 publications

(70 citation statements)

References 39 publications

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“…However, the relevance of cytoplasmic SIRT3 needs to be carefully investigated in future studies. In a very recent study from our laboratory, we found that SIRT3 is overexpressed in human melanoma cells and clinical melanoma tissues (58). Further, a short hairpin RNA (shRNA)-mediated knockdown of SIRT3 was found to impart significant anti-proliferative effects in multiple human melanoma cell lines (58).…”

Section: Mitochondrial Sirts and Their Molecular Targets: Relevance Tmentioning

confidence: 95%

“…In a very recent study from our laboratory, we found that SIRT3 is overexpressed in human melanoma cells and clinical melanoma tissues (58). Further, a short hairpin RNA (shRNA)-mediated knockdown of SIRT3 was found to impart significant anti-proliferative effects in multiple human melanoma cell lines (58). Conversely, forced exogenous overexpression of SIRT3 promoted enhanced proliferative potential of Hs294T melanoma cells and normal immortalized Mel-ST melanocytes (58).…”

Section: Mitochondrial Sirts and Their Molecular Targets: Relevance Tmentioning

confidence: 95%

“…Further, a short hairpin RNA (shRNA)-mediated knockdown of SIRT3 was found to impart significant anti-proliferative effects in multiple human melanoma cell lines (58). Conversely, forced exogenous overexpression of SIRT3 promoted enhanced proliferative potential of Hs294T melanoma cells and normal immortalized Mel-ST melanocytes (58). In addition, SIRT3 knockdown also resulted in a decrease in tumor growth in vivo in a xenograft model (58).…”

Section: Mitochondrial Sirts and Their Molecular Targets: Relevance Tmentioning

confidence: 99%

“…Conversely, forced exogenous overexpression of SIRT3 promoted enhanced proliferative potential of Hs294T melanoma cells and normal immortalized Mel-ST melanocytes (58). In addition, SIRT3 knockdown also resulted in a decrease in tumor growth in vivo in a xenograft model (58). In addition, limited information is available regarding mutation(s) in SIRT3 and its role in cancer.…”

Section: Mitochondrial Sirts and Their Molecular Targets: Relevance Tmentioning

confidence: 99%

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Mitochondrial Sirtuins in Cancer: Emerging Roles and Therapeutic Potential

George

Ahmad

2016

Cancer Research

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The past few decades have witnessed a furious attention of scientific community towards identifying novel molecular factors and targets which could be exploited for drug development for cancer management. One such factor is the sirtuin (SIRT) family of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases. The role of SIRTs in cancer is extremely complex, with dichotomous functions depending on cell contexts. Mammalian SIRTs (SIRT1–7), differ in their cellular localization and biological functions. Amongst these, SIRT -3, -4, and -5 are located in the mitochondria and are being carefully investigated. These mitochondrial SIRTs (mtSIRTs) regulate multiple cellular and physiological processes, including cell cycle, gene expression, cell viability, stress response, metabolism and energy homeostasis. Recent research suggests that mtSIRTs influence tumors by regulating the metabolic state of the cell. While the research on the role of mtSIRTs in cancer is still in its infancy, studies have suggested tumor suppressor as well as tumor promoter roles for them. This review is focused on discussing an up-to-date information about the roles and functional relevance of mtSIRTs (SIRT -3, -4, -5) in cancers. We have also provided a critical discussion and our perspective on their dual roles, as tumor promoter versus tumor suppressor, in cancer.

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Section: Mitochondrial Sirts and Their Molecular Targets: Relevance Tmentioning

confidence: 95%

Section: Mitochondrial Sirts and Their Molecular Targets: Relevance Tmentioning

confidence: 95%

Section: Mitochondrial Sirts and Their Molecular Targets: Relevance Tmentioning

confidence: 99%

Section: Mitochondrial Sirts and Their Molecular Targets: Relevance Tmentioning

confidence: 99%

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Mitochondrial Sirtuins in Cancer: Emerging Roles and Therapeutic Potential

George

Ahmad

2016

Cancer Research

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“…Oncogenic properties of SIRT3 are attributed to its actions in stimulation of proliferation, resistance to oxidative stress, and suppression of apoptosis. SIRT3 could play an oncogenic role in a spectrum of cancers including oral squamous cell carcinoma [58], breast cancer [59], esophageal cancer [60], gastric cancer [61], colorectal cancer [62], and melanoma cell lines [63].…”

Section: Changes In Sirtuin 3 Expression In Carcinogenesismentioning

confidence: 99%

Changes in the Expression and the Role of Sirtuin 3 in Cancer Cells and in Cardiovascular Health and Disease

Özden¹,

Tural²

2018

Gene Expression and Regulation in Mammalian Cells - Transcription Toward the Establishment of Novel Therapeutics

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Sirtuin 3, an NAD + -dependent deacetylase, whose expression is considered a marker in life extension, is downregulated with age and in various diseases. Sirtuin 3 is predominantly localized to the mitochondria and considered a fidelity protein for the integrity and function of this organelle. Some studies report its localization in the nucleus to regulate the expression of stress response-related genes and that reduced expression of SIRT3 produces a cellular milieu permissive for human pathologies. Since the expression and activity of Sirtuin 3 are important for the regulation of antioxidant defense, metabolism, and apoptosis initiation, the expression of SIRT3 is also important in the context of ageassociated illnesses. A variety of small molecules are being developed to modulate the expression or activity of Sirtuin 3 and are potentially a valuable strategy to change mitochondrial acetylome to treat several diseases. The AMPK-PGC1α-SIRT3 axis plays a critical role in preserving mitochondrial biogenesis and function. Here, we summarize how changes in Sirtuin 3 expression are regulated in cancer and dysfunctions in cardiovascular diseases. The potential therapeutic strategies by targeting Sirtuin 3 expression to improve mitochondrial function in cancer and cardiovascular diseases are summarized.

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Upregulation of cell surface GD3 ganglioside phenotype is associated with human melanoma brain metastasis

Ramos

Bustos

et al. 2020

Molecular Oncology

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Melanoma metastasis to the brain is one of the most frequent extracranial brain tumors. Cell surface gangliosides are elevated in melanoma metastasis; however, the metabolic regulatory mechanisms that govern these specific changes are poorly understood in melanoma particularly brain metastases (MBM) development. We found ganglioside GD3 levels significantly upregulated in MBM compared to lymph node metastasis (LNM) but not for other melanoma gangliosides. Moreover, we demonstrated an upregulation of ST8SIA1 (GD3 synthase) as melanoma progresses from melanocytes to MBM cells. Using RNA‐ISH on FFPE specimens, we evaluated ST8SIA1 expression in primary melanomas (PRM) ( n = 23), LNM and visceral metastasis ( n = 45), and MBM ( n = 39). ST8SIA1 was significantly enhanced in MBM compared to all other specimens. ST8SIA1 expression was assessed in clinically well‐annotated melanoma patients from multicenters with AJCC stage III B‐D LNM ( n = 58) with 14‐year follow‐up. High ST8SIA1 expression was significantly associated with poor overall survival (HR = 3.24; 95% CI, 1.19–8.86, P = 0.02). In a nude mouse human xenograft melanoma brain metastasis model, MBM variants had higher ST8SIA1 expression than their respective cutaneous melanoma variants. Elevated ST8SIA1 expression enhances levels of cell surface GD3, a phenotype that favors MBM development, hence associated with very poor prognosis. Functional assays demonstrated that ST8SIA1 overexpression enhanced cell proliferation and colony formation, whereby ST8SIA1 knockdown had opposite effects. Icaritin a plant‐derived phytoestrogen treatment significantly inhibited cell growth in high GD3‐positive MBM cells through targeting the canonical NFκB pathway. The study demonstrates GD3 phenotype associates with melanoma progression and poor outcome.

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Pro-Proliferative Function of Mitochondrial Sirtuin Deacetylase SIRT3 in Human Melanoma

Cited by 69 publications

References 39 publications

Mitochondrial Sirtuins in Cancer: Emerging Roles and Therapeutic Potential

Mitochondrial Sirtuins in Cancer: Emerging Roles and Therapeutic Potential

Changes in the Expression and the Role of Sirtuin 3 in Cancer Cells and in Cardiovascular Health and Disease

Upregulation of cell surface GD3 ganglioside phenotype is associated with human melanoma brain metastasis

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