Premium
Role of the transcription factor Yin Yang 1 in non‐small cell lung cancer
Author(s) -
BOUCHERAT Olivier,
CHABOT Sophie,
BOURGEOIS Alice,
PROVENCHER Steeve,
PAULIN Roxane,
MALTAIS François,
BONNET Sébastien
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.699.8
Subject(s) - lung cancer , cancer research , adenocarcinoma , ectopic expression , biology , cell growth , small interfering rna , cancer , immunohistochemistry , transcription factor , cell , a549 cell , medicine , pathology , oncology , transfection , cell culture , gene , biochemistry , genetics
Background Lung cancer is the most prevalent cancer type worldwide by both diagnosis and mortality, with non‐small cell lung cancers (NSCLCs) featuring as the most common histological subtype, the latter of which consists of squamous (epidermoid), adenocarcinoma, and large cell carcinoma. Rates of lung cancer will continue to rise owing to high levels of cigarette consumption and aging populations. Despite increased surgical resection rates, optimization of chemo‐radiotherapy and the introduction of targeted therapies, the treatment outcome for NSCLC remains poor. Therefore, identification of new molecular targets, which are essential for proliferation of tumor cells, will benefit both treatment and chemoprevention of NSCLC. The Yin Yang 1 (YY1) transcription factor has a pivotal role in normal biological processes such as development, differentiation, replication and cell proliferation exerting its effects on a huge number of genes involved in these processes. Due to its functions during lung morphogenesis, we hypothesize that YY1 is overexpressed and contributes to the pro‐proliferative and anti‐apoptotic phenotype of cancerous cells. Method/Results Expression level of YY1 was first examined by immunohistochemistry (n=5) and western blot (n=11) in resected tumor tissue of NSCLC patients (stages I–III) and compared to adjacent non‐cancerous lung tissue. Results showed that YY1 expression is significantly increased in squamous cell carcinoma and adenocarcinoma of the lung. A greater proliferation rate (Ki67 labeling) was associated with strong YY1 expression in these human lung tumors. In vitro, transient transfection experiments with A549 lung adenocarcinoma cells showed that depletion of YY1 levels by short interfering RNA reduced proliferation (Ki67 labeling and MTT assay, p<0,001), resistance to apoptosis (Annexin V assay, cleaved caspase‐3 expression, p<0,05) and migration (wound healing assay, p<0,001). In addition, YY1 knockdown improved in vitro NSCLC sensitivity to Etoposide/Cisplatin, two chemotherapeutic agents. Conclusion Taken together, these findings suggest that up‐regulation of YY1 plays an important role in the development of lung cancer. Susceptibility of YY1‐depleted A549 cells and YY1 heterozygous mice to induce tumors is currently under investigation. Analysis of YY1 expression in a larger cohort of patients may reveal prognostic information and deserves further study. Support or Funding Information None