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

Long non–coding RNA {type:entrez-nucleotide,attrs:{text:AC020978,term_id:28933544,term_text:AC020978}}AC020978 (lncRNA {type:entrez-nucleotide,attrs:{text:AC020978,term_id:28933544,term_text:AC020978}}AC020978) is an oncogenic regulator of non–small cell lung cancer (NSCLC). However, the function of {type:entrez-nucleotide,attrs:{text:AC020978,term_id:28933544,term_text:AC020978}}AC020978 in regulating NSCLC metastasis and the potential molecular mechanism remains largely unknown. In this study, we evaluated the expression levels of {type:entrez-nucleotide,attrs:{text:AC020978,term_id:28933544,term_text:AC020978}}AC020978 in a series of NSCLC tissues using FISH assays and found that higher {type:entrez-nucleotide,attrs:{text:AC020978,term_id:28933544,term_text:AC020978}}AC020978 expression levels were closely associated with metastasis and unfavorable prognosis. Functional studies showed that {type:entrez-nucleotide,attrs:{text:AC020978,term_id:28933544,term_text:AC020978}}AC020978 promoted NSCLC migration and invasion both in vitro and in vivo. Further investigation demonstrated that {type:entrez-nucleotide,attrs:{text:AC020978,term_id:28933544,term_text:AC020978}}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 {type:entrez-nucleotide,attrs:{text:AC020978,term_id:28933544,term_text:AC020978}}AC020978‐overexpressed NSCLC cells. RNA sequencing, bioinformatic analysis, and western blotting revealed that {type:entrez-nucleotide,attrs:{text:AC020978,term_id:28933544,term_text:AC020978}}AC020978 was associated with the AKT signaling pathway. Taken together, our findings revealed that {type:entrez-nucleotide,attrs:{text:AC020978,term_id:28933544,term_text:AC020978}}AC020978 might serve as a prognostic biomarker and activate the AKT pathway by stabilizing MDH2, leading to metastasis and progression of NSCLC.