ARNTL2 knockdown suppressed the invasion and migration of colon carcinoma: decreased SMOC2-EMT expression through inactivation of PI3K/AKT pathway.

ABSTRACT: ARNTL2 is a transcriptional activator implicated in the molecular clock feedback system and is overexpressed in some malignant tumors. This study aimed to detect the effects of ARNTL2 knockdown by siRNA on the proliferation and invasion of colon carcinoma and clarify the molecular mechanisms of ARNTL2 in the development of colon carcinoma (CC). The CC microarray dataset GSE50760 was downloaded from the Gene Expression Omnibus (GEO) database. The expression levels of ARNTL2 in CC tissues and cancer cells were analyzed by immunohistochemistry and western blot, respectively. The knockdown of ARNTL2 expression was induced by RNA interference in colon cancer cells. The proliferation was detected by Cell Counting Kit-8 and clonal formation assays. The invasion and migration in vitro were detected by wound healing and transwell assays. Besides, a tumorigenicity test in the nude mice was performed to confirm whether ARNTL2 expression promoted the proliferation and invasion of CC cells. Furthermore, the expression of epithelial-mesenchymal transition (EMT) and PI3K/AKT signaling pathway-related factors were analyzed by western blot. Results showed that bioinformatics analysis found that ARNTL2 was upregulated in CC tissues. ARNTL2 was highly expressed in tissues and CC cells. Knockdown of ARNTL2 inhibited CC cells viability, colony formation, migration activity and reduced the size of tumors in the nude mice. Moreover, knockdown of ARNTL2 suppressed the expression of SMOC2, which may be the target gene of ARNTL2, and simultaneously inhibited the expression of EMT and PI3K/AKT signaling pathway-related factors. Taken together, downregulation of ARNTL2 could suppress CC cell proliferation and migration via SMOC2-EMT through inactivation of PI3K/AKT signaling pathway.

SUBMITTER: Lu M 

PROVIDER: S-EPMC7191172 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature