KIN17 modulates cell proliferation and migration through the WNT/β-catenin signal pathways in non-small cell lung cancer

Abstract

Abstract Background KIN17 DNA and RNA binding protein (KIN17) regulates the tumorigenesis of a variety of human cancers. Non-small cell lung cancer’s (NSCLC) molecular mechanisms for cancer metastasis and growth, however, are still unknown. Methods KIN17’s expression pattern as well as its prognostic value in LUAD patients was examined utilizing bioinformatics, and KIN17 co-expression network was enriched by the KEGG pathway and built via protein-protein interaction (PPI) network. Western blotting and Real-time quantitative PCR were employed to find Kin17 expression in NSCLC cells. Moreover, total amounts of EMT, WNT-related proteins, and β-catenin were also found using Western blotting. The expression of N‑cadherin, E-cadherin, and Vimentin was examined using immunohistochemical and immunofluorescent staining. The invasive and proliferative capacities of cancer cells were examined in vitro using wound healing, proliferation, cell cycle, transwell migration, and apoptosis. The impacts of KIN17 on the invasive and proliferative capacities in vivo were studied using the tumor xenograft model. Results On the basis of the TIMRE database, the mRNA expression of KIN was shown to be considerably higher in tumor tissues in contrast to adjacent normal tissues, and the protein expression of KIN was found to be considerably higher in LUAD from the National Cancer Institute. Then, in the LUAD from the TCGA database, patients with increased KIN17 expression had lowest disease free survival (DFS). The co-expression network of KIN17 enriched pathways were obtained by KEGG enrichment analysis and found to be linked to the tumorigenesis and development, including tight junction, WNT signaling pathway, regulation of actin cytoskeleton, and focal adhesion. In NSCLC cells, KIN17 was also upregulated in H1299 cell. With an increased expression of E-cadherin and a reduced expression of Vimentin and N-cadherin, KIN17 knockdown in H1299 cells greatly inhibited the ability of cells to invade, proliferate, and migrate. KIN17 knockdown likewise impaired WNT/β-catenin signal pathways, as indicated by downregulated expression of the WNT and β-catenin in vitro. Furthermore, KIN17 knockdown significantly reduced tumor renewal in NSCLC xenograft models. Conclusions By blocking the WNT/β-catenin pathway, KIN17 knockdown prevents EMT, NSCLC proliferation, and invasion.