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Silencing Sirtuin 6 induces cell cycle arrest and apoptosis in non-small cell lung cancer cell lines

Varunkumar Krishnamoorthy1, Ravikumar Vilwanathan1

  • 1Cancer Biology Laboratory, Department of Biochemistry, School of Life Sciences, Bharathidasan University, Tiruchirappalli, Tamil Nadu 620 024, India.

Genomics
|May 4, 2020
PubMed

Insights

Sirtuins, enzymes involved in cell regulation, were studied in non-small cell lung cancer (NSCLC). SIRT6 was found to promote NSCLC growth, suggesting its silencing could be a novel lung cancer therapy.

Area of Science:

  • Molecular Biology
  • Oncology

Background:

  • Sirtuins (SIRTs) are NAD-dependent enzymes with critical roles in carcinogenesis, acting as either tumor suppressors or promoters.
  • While sirtuins are implicated in various cancers, their specific roles in non-small cell lung cancer (NSCLC) remain under-investigated.

Purpose of the Study:

  • This study aimed to investigate the multifaceted roles of sirtuins in NSCLC cells.
  • Specifically, the research focused on evaluating the expression and functional impact of sirtuins in NSCLC progression.

Main Methods:

  • Messenger RNA (mRNA) and protein expression levels of sirtuins were assessed using quantitative reverse transcription PCR (RTPCR) and Western blot analysis.
  • Small interfering RNA (siRNA) was employed to silence SIRT6 expression in NSCLC cell lines.

Main Results:

  • SIRT6 was found to be significantly overexpressed in multiple NSCLC cell lines (NCI-H520, A549, NCI-H460) compared to normal bronchial epithelial cells (BEAS-2B).
  • Silencing of SIRT6 in NSCLC cells led to the activation of the p53/p21 pathway, resulting in inhibited cell proliferation, cell cycle arrest, and induction of apoptosis.

Conclusions:

  • SIRT6 functions as a tumor promoter in the development, progression, and regulation of NSCLC.
  • Targeted silencing of SIRT6 presents a potential novel therapeutic strategy for treating lung cancer.
Keywords:
EpigeneticsNSCLCSIRT6p53/p21siRNA

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