Down-Regulation of HBXIP Inhibits Non-Small Cell Lung Cancer Growth and Enhances the Anti-Tumor Immunity of Mice by Reducing NRP-1.

OBJECTIVE

Hepatitis B X-interacting protein (HBXIP) interacts with hepatitis B virus X protein to participate in the replication of the hepatitis B virus and carcinogenesis. Cellular growth and metastasis of non-small-cell lung cancer (NSCLC) are repressed by HBXIP inhibition. However, the role and mechanism of HBXIP on NSCLC cell growth remain unknown.

MATERIALS

Expression of HBXIP was assessed by qRT-PCR and Western blot. siRNA targeting HBXIP was applied to detect cell viability and proliferation by MTT and colony formation assays. tumor growth was assessed, and anti-tumor immunity was determined by flow cytometry. The downstream partners involved in HBXIP-mediated tumorigenesis were detected by Western blot.

RESULTS

Expression of HBXIP and neuropilin1-1 (NRP-1) was higher in NSCLC tissues and cells than in paracancerous tissues and human lung epithelial cells. siRNA-mediated knockdown of HBXIP decreased the cell viability of NSCLC and suppressed proliferation. Protein expression of Lin28B and NRP-1 was reduced by the knockdown of HBXIP, and over-expression of Lin28B attenuated the HBXIP silence-induced decrease of NRP-1. tumor growth was suppressed by HBXIP silencing, and the knockdown of HBXIP enhanced anti-tumor immunity through the increase of CD4+ and CD8+ T lymphocytes.

CONCLUSION

Down-regulation of HBXIP reduced Lin28B-mediated NRP-1 to suppress NSCLC cell growth and enhance anti-tumor immunity.