1. Academic Validation
  2. The HDAC2-MTA3 interaction induces nonsmall cell lung cancer cell migration and invasion by targeting c-Myc and cyclin D1

The HDAC2-MTA3 interaction induces nonsmall cell lung cancer cell migration and invasion by targeting c-Myc and cyclin D1

  • Mol Carcinog. 2023 Jul 4. doi: 10.1002/mc.23604.
Bin Wang 1 Xiao-Yong Shen 1 Lin-Yue Pan 2 Zheng Li 1 Chun-Ji Chen 1 Yuan-Shan Yao 1 Dong-Fang Tang 1 Wen Gao 1
Affiliations

Affiliations

  • 1 Shanghai Key Laboratory of Clinical Geriatric Medicine, Department of Thoracic Surgery, The Affiliated Huadong Hospital of Fudan University, Shanghai, China.
  • 2 Department of Respiration, The Affiliated Zhongshan Hospital of Fudan University, Shanghai, China.
Abstract

Genome-wide association studies have identified numerous single-nucleotide polymorphisms (SNPs) associated with lung cancer; however, the functions of histone deacetylase 2 (HDAC2) rs13213007 and HDAC2 in nonsmall cell lung Cancer (NSCLC) remain unclear. Here we identified HDAC2 rs13213007 as a risk SNP and showed that HDAC2 was upregulated in both peripheral blood mononuclear cells (PBMCs) and NSCLC tissues with the rs13213007 A/A genotype compared with those with the rs13213007 G/G or G/A genotype. Patient clinical data indicated strong associations between rs13213007 genotype and N classification. Immunohistochemical staining confirmed that higher expression of HDAC2 was associated with NSCLC progression. Furthermore, we generated 293T cells with the rs13213007 A/A genotype using CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 gene editing. Chromatin immunoprecipitation Sequencing followed by motif analysis showed that HDAC2 can bind to c-Myc in rs13213007 A/A 293T cells. Cell Counting Kit-8, colony formation, wound-healing, and Transwell assays revealed that HDAC2 upregulates c-Myc and cyclin D1 expression and promotes NSCLC cell proliferation, migration, and invasion. Co-immunoprecipitation, quantitative reverse transcription-polymerase chain reaction, and western blot analysis assays showed that MTA3 interacts with HDAC2, decreases HDAC2 expression, and rescues the migration and invasion abilities of NSCLC cells. Taken together, these findings identify HDAC2 as a potential therapeutic biomarker in NSCLC.

Keywords

MTA3; histone deacetylase 2; migration and invasion; nonsmall cell lung cancer; single-nucleotide polymorphism.

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