Silencing HIPPI Suppresses Tumor Progression in Non-Small-Cell Lung Cancer by Inhibiting DNA Replication.

ABSTRACT

INTRODUCTION: Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for approximately 80%-85% of all cases of lung cancer. Huntingtin interacting protein-1 interacting protein (HIPPI) is a transcription regulator and plays an important role in apoptotic cell death. However, the role of HIPPI in NSCLC remains unclear. METHODS: Immunohistochemistry (IHC) and qRT-PCR were performed for expression analysis. The roles of HIPPI were studied using cell counting kit-8 (CCK-8), colony formation, flow cytometry, wound healing, Transwell invasion assays and mouse xenograft model. Gene microarray analysis and bioinformatics analysis were used to identify differentially expressed genes after HIPPI silencing. RESULTS: HIPPI is highly expressed in NSCLC tissues relative to adjacent normal tissues. Targeting HIPPI by RNA interference inhibits NSCLC cell proliferation in vitro and tumor growth in vivo. HIPPI silencing also attenuates cell migration and invasion and enhances cisplatin sensitivity in NSCLC cells. Mechanistic investigation suggests that HIPPI can positively regulate the expression of MCM2, MCM6 and MCM8, which are key regulators of DNA replication. Furthermore, consistent with HIPPI, MCM2, MCM6 and MCM8 are also upregulated in NSCLC tissues. CONCLUSION: Our study highlights the importance of HIPPI for tumor biology in NSCLC and suggests that HIPPI may be a potential therapeutic target for NSCLC treatment.