LncRNA MAFG-AS1 promotes the progression of colorectal cancer by sponging miR-147b and activation of NDUFA4

Abstract

Researchers have shown that long noncoding RNAs (lncRNAs) are closely associated with the pathogenesis of colorectal cancer (CRC). In here, we aimed to explore the function of lncRNA MAFG-AS1 in tumorigenesis of CRC. Firstly, we found that the expression of MAFG-AS1 was upregulated in CRC tissues and positively correlated with the advanced tumor stage. A reciprocal repression was found between MAFG-AS1 and miR-147b. The expression of miR-147b was downregulated in CRC tissues and inversely correlated with MAFG-AS1. Both the low-expression of miR-147b expression and the advanced tumor stage were independent factor for poor survival probability. Furthermore, overexpression of MAFG-AS1 promoted cell proliferation, cell cycle progression, and invasion, and inhibited apoptosis, while transduction of miR-147b partially reversed the effect of MAFG-AS1 on cellular processes. Consistently, stable over-expression of MAFG-AS1 contributed to the growth of colon cancer cell xenografts in vivo. NDUFA4 was identified as a direct target of miR-147b and knockdown of NDUFA4 abolished the oncogenic role of miR-147b inhibitor. Besides, MAFG-AS1 contributed to cell glycolysis by sponging miR-147b and activation of NDUFA4, causing an upregulation of PDK1, PFK1 and PKM2. Taken together, our study suggested that MAFG-AS1 functions as a novel oncogenic lncRNA in the development of CRC by regulating miR-147b/NDUFA4.