# Role of sirtuin 6 in melanoma development and progression

> **NIH VA I01** · WM S. MIDDLETON MEMORIAL VETERANS HOSP · 2022 · —

## Abstract

Melanoma incidences are increasing rapidly with 100,350 cases predicted in 2020 in the US. Further,
melanoma is a significant problem in Veterans, and it is among the five most frequently diagnosed cancers
among VA cancer patients. Malignant melanoma is one of the deadliest forms of cancer, and the existing
therapeutics, including recently approved BRAF inhibitors, have not been fully effective in melanoma
management due to acquired resistance. Therefore, novel target-based approaches are needed for the
management of this neoplasm. We have an ongoing research program to define the role of sirtuins in
melanoma. The mammalian sirtuins constitute a family of seven members (SIRT1 – SIRT7), which play critical
roles in important cellular processes, and are involved in a variety of diseases, including cancer. The role of
SIRTs in cancer is complex, and they appear to have dichotomous functions depending on cell context. Recent
studies have implicated sirtuin 6 (SIRT6), a predominantly nuclear protein, in regulating pathways involved in
gene transcription, glucose homeostasis, DNA repair and telomere integrity. SIRT6 has been found to
suppress tumorigenesis in the intestine and liver. However, SIRT6 also has a pro-proliferative role in skin and
prostate cancer, suggesting that its function may be tissue- and context- dependent. Interestingly, SIRT6 has
also been shown to modulate epithelial-mesenchymal transition (EMT) and promote metastasis in certain
cancer types. In a recent study, we have demonstrated that SIRT6 is overexpressed in human melanoma cells
and tissues, and SIRT6 inhibition via shRNA-mediated RNA interference resulted in a marked antiproliferative
response (growth inhibition, cell cycle alternation, inhibition of cell migration, senescence and autophagy
dysregulation) in melanoma cells. Our preliminary data and published study together with other published
research provide a strong scientific premise to our investigation into the role and potential therapeutic
significance of SIRT6 in melanoma and supports our proposed hypothesis that SIRT6 plays a critical role in
melanocytic transformation and melanoma progression and together with other driver pathways, can be
therapeutically exploited for melanoma management. The following specific aims are proposed: 1) To define
the role of SIRT6 in melanoma development and progression and its association with critical melanoma driver
pathways employing a tissue microarray (TMA) created from retrospective melanoma tissues from Veteran
patients. In this aim, we will determine the role of SIRT6 in melanoma as well as its association with critical
melanoma driver pathways (RAS/RAF/MEK/ERK-, and p16/cyclin D-CDK4/6-RB- pathways); 2) To determine
the functional and mechanistic significance of SIRT6 in melanoma. In this aim, we will determine the effect of
CRISPR/Cas9 mediated SIRT6 deletion on growth and progression of melanoma cells in vitro and in vivo; and
3) To determine the therapeutic significance ...

## Key facts

- **NIH application ID:** 10115889
- **Project number:** 1I01CX002210-01
- **Recipient organization:** WM S. MIDDLETON MEMORIAL VETERANS HOSP
- **Principal Investigator:** Nihal Ahmad
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2021-10-01 → 2025-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10115889

## Citation

> US National Institutes of Health, RePORTER application 10115889, Role of sirtuin 6 in melanoma development and progression (1I01CX002210-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10115889. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*