Alveolar type 2 cells marker gene inhibits epithelial-to-mesenchymal transition by upregulating and suppressing WNT/β-catenin pathway in non-small cell lung cancer.

INTRODUCTION

Surfactant Protein C gene () is a marker gene of alveolar type 2 cells (AT2), which are the key structures of alveoli. Mutations or deletions in cause idiopathic pulmonary fibrosis (IPF). Importantly, IPF is an independent risk factor for non-small cell lung cancer (NSCLC). It suggests that abnormal expression of may be relevant to development of NSCLC. However, the function and mechanism of in NSCLC are still poor understood until now.

METHODS

The expression of and the relationship between and prognosis of NSCLC were analyzed in TCGA database and our collected clinical NSCLC tissues. Subsequently, the function and mechanism of in NSCLC were explored by RNA-sequence, qRT-PCR, Western blot, Immunohistochemical, Wound-healing, Millicell, Transwell assays and mouse tumor xenograft model.

RESULTS

was dramatically downregulated in NSCLC tissues from TCGA database and 40 out of 46 collected clinical LUAD tissues compared with adjacent non-tumor tissues. Low expression of was associated with poor prognosis of LUAD by TCGA database. Importantly, we confirmed that overexpression of significantly inhibited Epithelial-to-Mesenchymal Transition (EMT) process of NSCLC cells by upregulating and then inactivating WNT/β-catenin pathway and . Particularly, we discovered that low expression of was associated with EMT process and low expression of in NSCLC tissues.

CONCLUSION

Our study revealed a novel mechanism of in NSCLC development. Meanwhile, it also might provide a new clue for exploring the molecular mechanism about NSCLC development in patients with IPF in the future.