LncRNA AC020978 facilitates non–small cell lung cancer progression by interacting with malate dehydrogenase 2 and activating the AKT pathway

Abstract

Long non–coding RNA AC020978 (lncRNA AC020978) is an oncogenic regulator of non–small cell lung cancer (NSCLC). However, the function of AC020978 in regulating NSCLC metastasis and the potential molecular mechanism remains largely unknown. In this study, we evaluated the expression levels of AC020978 in a series of NSCLC tissues using FISH assays and found that higher AC020978 expression levels were closely associated with metastasis and unfavorable prognosis. Functional studies showed that AC020978 promoted NSCLC migration and invasion both in vitro and in vivo. Further investigation demonstrated that AC020978 interacted with malate dehydrogenase 2 (MDH2) and maintained MDH2 stability. Knockdown of MDH2 weakened the facilitating effect on cell metastasis and 2‐hydroxyglutarate (2‐HG) metabolism in AC020978‐overexpressed NSCLC cells. RNA sequencing, bioinformatic analysis, and western blotting revealed that AC020978 was associated with the AKT signaling pathway. Taken together, our findings revealed that AC020978 might serve as a prognostic biomarker and activate the AKT pathway by stabilizing MDH2, leading to metastasis and progression of NSCLC.

Abstract

We identified the metastasis‐related function of lncRNA AC020978 in NSCLC, which directly interacts with MDH2 and promotes migration and invasion of lung cancer through the AC020978/MDH2/AKT axis.