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Updated: May 9, 2026
Deacetylation Assays to Unravel the Interplay between Sirtuins (SIRT2) and Specific Protein-substrates
Published on: February 27, 2016
Regulation of SIRT2 levels for human non-small cell lung cancer therapy
Ziming Li1, Qian Reuben Xie, Zhiwei Chen
1Shanghai Lung Cancer Center, Shanghai Chest Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200030, People's Republic of China.
Abstract:
Seven Sirtuin family members (SIRT1-7), comprising a family of NAD+-dependent protein deacetylases and ADP-ribosyltransferases, are key proteins that regulate multiple physiological processes. SIRT2 was recently reported to play an important role in carcinogenesis. However, its role in non-small cell lung cancer (NSCLC) has not yet been investigated. In this study, we analyzed the expression pattern of SIRT2 in NSCLC tissues from clinical patients and in cell lines, and found that SIRT2 was significantly down-regulated at both the mRNA and protein levels in tumor than non-tumor tissues or cells, which were corroborated by the NSCLC tissue microarray results. Overexpression of SIRT2 in A549 and H1299 cells caused cell proliferation inhibition, cell apoptosis induction and cell cycle arrest. Further analysis showed that SIRT2 overexpression increased the ROS (reactive oxygen species) production and p27 levels. Moreover, up-regulation of SIRT2 in NSCLC cells increased the sensitivity to Cisplatin treatment. Taken together, our results implied that down-regulation of SIRT2 was associated with NSCLC, and regulation of SIRT2 might be an important target for NSCLC therapy.
Insights
Sirtuin 2 (SIRT2) is down-regulated in non-small cell lung cancer (NSCLC). Restoring SIRT2 inhibits tumor growth, induces apoptosis, and enhances chemotherapy sensitivity in NSCLC.
Area of Science:
- Molecular Biology
- Oncology
Background:
- Sirtuins (SIRTs) are NAD+-dependent enzymes regulating physiological processes.
- SIRT2 has been implicated in carcinogenesis, but its role in non-small cell lung cancer (NSCLC) remains unclear.
Purpose of the Study:
- To investigate the expression and function of SIRT2 in NSCLC.
- To determine if SIRT2 could be a therapeutic target for NSCLC.
Main Methods:
- Analysis of SIRT2 expression in NSCLC patient tissues and cell lines.
- Functional studies involving SIRT2 overexpression in NSCLC cell lines (A549, H1299).
- Assessment of cell proliferation, apoptosis, cell cycle, reactive oxygen species (ROS) production, p27 levels, and cisplatin sensitivity.
Main Results:
- SIRT2 was significantly downregulated in NSCLC tissues and cells at both mRNA and protein levels.
- Overexpression of SIRT2 inhibited NSCLC cell proliferation, induced apoptosis, and caused cell cycle arrest.
- SIRT2 upregulation increased ROS production, elevated p27 levels, and enhanced sensitivity to cisplatin treatment.
Conclusions:
- Downregulation of SIRT2 is associated with NSCLC development.
- SIRT2 plays a tumor-suppressive role in NSCLC.
- Modulating SIRT2 may represent a promising therapeutic strategy for NSCLC.
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