LINC01123 acts as an oncogenic driver in lung adenocarcinoma by regulating the miR-4766-5p/PYCR1 axis

Abstract

Background: Lung adenocarcinoma remains one of the most significant threats to human life as it involves multiple etiologies, including alteration of oncogenes or tumor-inhibitory genes. Long non-coding RNAs (lncRNAs) have been reported to have both cancer promoting and cancer inhibiting effects. In this work, we investigated the function and mechanism of lncRNA LINC01123 in lung adenocarcinoma.

Methods: The expression of LINC01123, miR-4766-5p, and PYCR1 (pyrroline-5-carboxylate reductase 1) mRNA was analyzed by RT-qPCR. The protein expression levels of PYCR1 and the apoptosis-related proteins (Bax and Bcl-2) were determined by western blotting. Cell proliferation and migration were determined by CCK-8 and wound-healing assays, respectively. Tumor growth in nude mice and Ki67 immunohistochemical staining were used to determine the in vivo role of LINC01123. The putative binding relationships miR-4766-5p has with LINC01123 and PYCR1, which had been identified by analysis of public databases, were validated through RIP and dual-luciferase reporter assays.

Results: LINC01123 and PYCR1 overexpression and miR-4766-5p downregulation were shown to occur in lung adenocarcinoma samples. LINC01123 depletion repressed lung adenocarcinoma cell growth and migration and blocked the development of solid tumors in an animal model. Moreover, LINC01123 bound directly to miR-4766-5p, the downregulation of which attenuated the anticancer effects of LINC01123 depletion in lung adenocarcinoma cells. MiR-4766-5p directly targeted downstream PYCR1 to suppress PYCR1 expression. The repressive effects of PYCR1 knockdown on the migration and proliferation of lung adenocarcinoma cells were also partly abolished by miR-4766-5p downregulation.

Conclusion: Downregulation of LINC01123 represses lung adenocarcinoma progression. This suggests that LINC01123 functions as an oncogenic driver in lung adenocarcinoma by controlling the miR-4766-5p/PYCR1 axis.