J Gene Med. 2020 Jul 16:e3254. doi: 10.1002/jgm.3254. Online ahead of print.
BACKGROUND: Non-small cell lung cancer (NSCLC) is a lethal tumor bringing large number of cancer-related deaths globally. Long noncoding RNAs (lncRNAs) may modulate tumor initiation and metastasis. Although dysregulation of lncRNA cancer susceptibility 19 (CASC19) is validated in NSCLC, further exploration of CASC19-regulated mechanism in NSCLC is still needed.
METHODS: CASC19 expression was examined in NSCLC cells by RT-qPCR. The specific role of CASC19 in NSCLC was analyzed by CCK-8, EdU, transwell and western blot assays. The interaction between miR-301b-3p and CASC19 or low density lipoprotein receptor (LDLR) was confirmed by luciferase reporter and RIP assays.
RESULTS: CASC19 is markedly overexpressed in NSCLC. Its deficiency impairs cell proliferation as well as metastasis in NSCLC. Molecular mechanism experiments delineated that CASC19 negatively modulates the expression of miR-301b-3p and miR-301b-3p can bind with CASC19 in NSCLC. In addition, miR-301b-3p binds to LDLR to impair its expression in NSCLC. Finally, rescue experiments showed that miR-301b-3p inhibition or LDLR overexpression counteracted the CASC19 knockdown-mediated function on cell proliferation and metastasis in NSCLC.
CONCLUSIONS: CASC19 facilitates NSCLC cell proliferation and metastasis by targeting the miR-301b-3p/LDLR axis, offering a possible strategy for lncRNA-targeted treatment in NSCLC.