The lncRNA <i>MEG3</i> mediates renal cell cancer progression by regulating <i>ST3Gal1</i> transcription and EGFR sialylation

Abstract

Long noncoding RNAs (lncRNAs) have emerged as important regulators of cancer progression. Abnormal sialylation leads to renal cell carcinoma (RCC) malignancy. However, the mechanism by which the lncRNA maternally expressed gene 3 (<i>MEG3</i>) mediates RCC progression by regulating <i>ST3Gal1</i> transcription and EGFR sialylation is still unrevealed. Here, we found that the expression of <i>MEG3</i> was higher in adjacent tissues than in RCC tissues, as well as downregulated in RCC cell lines compared to expression in normal renal cells. The proliferation, migration and invasion of RCC cells transfected with <i>MEG3</i> was decreased, whereas knockdown of <i>MEG3</i> had the opposite effect. The proliferative and metastatic abilities of RCC cells <i>in vivo</i> were concordant with their behavior <i>in vitro</i><i>ST3Gal1</i> expression was dysregulated in RCC and was positively correlated with <i>MEG3</i> By applying bioinformatics, c-Jun (also known as JUN) was identified as a transcription factor predicted to bind the promoter of <i>ST3Gal1</i>, and altered <i>MEG3</i> levels resulted in changes to c-Jun expression. Furthermore, ST3Gal1 modulated EGFR sialylation to inhibit EGFR phosphorylation, which affected activation of the phosphoinositide 3-kinase (PI3K)-AKT pathway. Taken together, our findings provide a novel mechanism to elucidate the role of the <i>MEG3</i>-ST3Gal1-EGFR axis in RCC progression.