Ectodermal‑neural cortex 1 affects the biological function of lung cancer through the MAPK pathway.

Abstract

Ectodermal-neural cortex 1 (ENC1), a highly expressed protein in lung cancer tissues, was identified from the Cancer Genome Atlas (TCGA) database. The objective of the present study was to examine the effects of ENC1 on the biological functions of lung cancer cells. For this purpose, the expression of ENC1 was examined by RT-qPCR to compare mRNA expression levels between 28 lung cancer tissue samples and para-cancerous tissue samples. The association between ENC1 expression and clinicopathological features was evaluated between the 2 tissue types. Using RT-qPCR and western blot analysis, the expression of ENC1 was investigated in a normal lung cell line (16HBE) and 2 lung cancer cell lines (A549 and H1299). The effect of siRNA targeting ENC1 (si-ENC1) on the proliferation of A549 and H1299 cells was detected by CCK-8 assay at the indicated time points. Transwell assay was used to measure the migration and invasion of A549 and H1299 cells following transfection with siRNA targeting ENC1 (si-ENC1). The expression levels of several proteins related to migration and invasion were examined by western blot analysis. A mouse model of subcutaneous tumor xenotransplantation was established in nude mice to examine the effects of ENC1 downregulation on cancer cells. The results revealed that the expression of ENC1 in lung cancer tissues and lung cancer cells was significantly higher than that in para-cancerous tissues and non-cancer lung cells, respectively. The knockdown of ENC1 in the A549 and H1299 cells using si-ENC1 significantly decreased cell proliferation, migration and invasion compared with the untransfected cells. The knockdown of ENC1 significantly downregulated the levels of matrix metalloproteinase (MMP)2, MMP9, N-cadherin, p-c-Jun N-terminal kinase (JNK), p-extracellular signal-regulated kinase (ERK) and p-p38. The levels of E-cadherin were upregulated. In the mouse lung tumor model, reduced levels of ENC1 inhibited the growth of lung tumors. On the whole, the present study demonstrates that ENC1 is involved in the proliferation, migration and invasion of lung cancer cells, and may thus be an effective diagnostic target for certain cancers. The inhibition or reduction of ENC1 activity may represent a breakthrough in the treatment of lung cancer.