LINC00476 suppresses the progression of non-small cell lung cancer via inducing the ubiquitination of SETDB1

Background: Long non-coding RNAs are involved in the tumorigenesis of non-small cell lung cancer (NSCLC). This study aims to investigate whether LINC00476 affects the proliferation, invasion, and migration of NSCLC cells via SETDB1-activated Wnt/β-catenin pathway. Method: The expression of LINC00476, SETDB1, Wnt1, and β-catenin were determined in NSCLC tumor tissues and the paired adjacent tissues, as well as in NSCLC cell lines and bronchial epithelioid cell lines. Cell proliferation, invasion, and migration were determined using cell counting kit-8 assay and Transwell assay. The relationship between LINC00476 and SETDB1 was elucidated using RNA pull-down, RNA immunoprecipitation, and ubiquitination assays. Result: LINC00476 was significantly downregulated, while SETDB1, Wnt1, and β-catenin were upregulated in NSCLC tumor tissues and cell lines compared to the normal ones. Overexpression of LINC00476 promoted the proliferation, invasion, and migration of NSCLC cells, as well as suppressed tumor growth in the mouse xenograft. Meanwhile, overexpression of LINC00476 induced the degradation of SETDB1 via promoting its ubiquitination. The simultaneous overexpression of LINC00476 and SETDB1 negated the inhibition of LINC00476 overexpression on the proliferation, invasion, and migration of NSCLC cells. Conclusion: LINC00476 acts as a tumor suppressor in NSCLC via downregulating SETDB1, which provides a novel target in treating NSCLC.