LncRNA MEG3 mediates renal cell cancer progression by regulating ST3Gal1 transcription and EGFR sialylation

Abstract

Long noncoding RNAs (lncRNAs) have emerged as important regulators of cancer progression. Abnormal sialylation leads to renal cell cancer (RCC) malignancy. However, the mechanism of lncRNA maternally expressed gene 3 (MEG3) mediates RCC progression by regulating ST3Gal1 transcription and EGFR sialylation is still unrevealed. Here, we found that the expression of MEG3 was higher in adjacent tissues than that in RCC tissues, as well as downregulated in RCC cell lines than that in normal renal cells. The proliferation, migration and invasion of RCC cell transfected with MEG3 were decreased, while the MEG3-knockdown cells showed the reversed results. The proliferative and metastatic ability in vivo were concordant to the behavior in vitro. ST3Gal1 was dysregulated and positively correlated to MEG3. By applying bioinformatics, c-Jun was identified as a transcription factor of ST3Gal1, while altered MEG3 regulated c-Jun expression. Furthermore, ST3Gal1 modulated EGFR sialylation to inhibit EGFR phosphorylation, which affected the PI3K/AKT pathway activation. Taken together, our study provided a novel mechanism to elucidate the role of MEG3/ST3Gal1/EGFR axis in RCC progression.