miR-21 promotes non-small cell lung cancer cells growth by regulating fatty acid metabolism

Abstract

Background Lung cancer is one of the most common malignant tumors worldwide. CD36 is a receptor for fatty acids and plays an important role in regulating fatty acid metabolism, which is closely related to tumorigenesis and development. The regulation of miR-21 and its role in tumorigenesis have been extensively studied in recent years. However, the relationship between miR-21 and CD36 regulated fatty acid metabolism in human non-small cell lung cancer remains unknown. Methods In this study, lentivirus transfection, qRT-PCR, cell migration, immunofluorescence, and western blot were used to examine the relationship between miR-21 and CD36 regulated fatty acid metabolism and the regulation role of miR-21 in human non-small cell lung cancer. Results This study demonstrated that up-regulation of miR-21 promoted cell migration and cell growth in human non-small cell lung cancer cells. Moreover, the intracellular contents of lipids including cellular content of phospholipids, neutral lipids content, cellular content of triglycerides were significantly increased following miR-21 mimic treatment compared with control, and the levels of key lipid metabolic enzymes FASN, ACC1 and FABP5 were obviously enhanced in human non-small cell lung cancer cells. Furthermore, down-regulation of CD36 suppressed miR-21 regulated cell growth, migration and intracellular contents of lipids in human non-small cell lung cancer cells, which suggested that miR-21 promoted cell growth and migration of human non-small cell lung cancer cells through CD36 mediated fatty acid metabolism. Inhibition of miR-21 was revealed to inhibit cell growth, migration, intracellular contents of lipids, and CD36 protein expression level in human non-small cell lung cancer cells. In addition, PPARGC1B was a direct target of miR-21, and down-regulation of PPARGC1B reversed the inhibition of CD36 expression induced by miR-21 inhibitor. Conclusions These results explored the mechanism of miR-21 promoted non-small cell lung cancer and might provide a novel therapeutic method in treating non-small cell lung cancer in clinic.

Berberine Suppressed Tumor Growth through Regulating Fatty Acid Metabolism and Triggering Cell Apoptosis via Targeting FABPs

“…Lipids which mainly include fatty acids and cholesterol are vital sources of energy metabolism in the human body [33]. Studies suggested that to meet the needs of biosynthesis during high levels of proliferation, the reprogramming of fatty acid (FA) metabolism becomes essential in cancer cells [34].…”

<p>LncRNA SNHG9 is Downregulated in Non-Small Cell Lung Cancer and Suppressed miR-21 Through Methylation to Promote Cell Proliferation</p>

“…13 Another study reported that SNHG9 was downregulated in prostate cancer and predicted the survival of patients. 15 Therefore, SNHG9 may exhibit different expression patterns and play different roles in different types of malignancy. In our study, we found that SNHG9 was downregulated in NSCLC and its suppressive roles in NSCLC cell proliferation, which suggests that lncRNA SNHG9 may participate in the progression of NSCLC.…”

“…[16][17][18] It has been revealed that the upregulation of miR-21 promoted cell migration and cell growth in human non-small cell lung cancer cells through CD36 mediated fatty acid metabolism. 15 In addition, it was reported that the expression levels of miR-21 were elevated in NSCLC, and the expression of miR-21 was inversely correlated with overall survival of NSCLC patients, which indicated that miR-21 promoted the development of NSCLC. 19 In our study, we analyzed the TCGA dataset and observed downregulation of SNHG9 and its inverse correlation with miR-21 as well as its inhibitory roles in the regulation of the proliferation of non-small cell lung cancer (NSCLC) cells.…”

“…The effects of miR-21 have been widely investigated in different diseases including lung cancer. 15 MiR-21 was one of the first miRNAs identified in mammalian, which is located on chromosome 17 (17q.23.1) in the 11th intron of the TMEM49 (transmembrane protein 49) gene, precursor of VMP1 (vacuole membrane protein 1). [16][17][18] It has been revealed that the upregulation of miR-21 promoted cell migration and cell growth in human non-small cell lung cancer cells through CD36 mediated fatty acid metabolism.…”

The Emerging Role of MicroRNAs in NAFLD: Highlight of MicroRNA-29a in Modulating Oxidative Stress, Inflammation, and Beyond

“…Hepatocyte-specific knockout of miR-21 in mice improved HFD-induced steatosis through upregulation of multiple miR-21-targeted pathways governing lipid metabolism [145]. In lung cancer cells, inhibition of miR-21 was shown to restrain FA uptake by down-regulating CD36 protein expression [146].…”