当前位置: X-MOL 学术J. Cell Sci. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
The lncRNA MEG3 mediates renal cell cancer progression by regulating ST3Gal1 transcription and EGFR sialylation.
Journal of Cell Science ( IF 3.3 ) Pub Date : 2020-08-25 , DOI: 10.1242/jcs.244020
Aihong Gong 1, 2 , Xinyu Zhao 1 , Yue Pan 1 , Yu Qi 1 , Shuangda Li 1 , Yiran Huang 1 , Yanru Guo 1 , Xia Qi 1 , Wei Zheng 3 , Li Jia 4
Affiliation  

Aihong Gong, Xinyu Zhao, Yue Pan, Yu Qi, Shuangda Li, Yiran Huang, Yanru Guo, Xia Qi, Wei Zheng, and Li Jia

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 (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 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 MEG3 was decreased, whereas knockdown of MEG3 had the opposite effect. The proliferative and metastatic abilities of RCC cells in vivo were concordant with their behavior in vitro. ST3Gal1 expression was dysregulated in RCC and was positively correlated with MEG3. By applying bioinformatics, c-Jun (also known as JUN) was identified as a transcription factor predicted to bind the promoter of ST3Gal1, and altered MEG3 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 MEG3–ST3Gal1–EGFR axis in RCC progression.



中文翻译:

lncRNA MEG3 通过调节 ST3Gal1 转录和 EGFR 唾液酸化介导肾细胞癌进展。

龚爱红、赵新宇、潘悦、于琪、李双达、黄怡然、郭艳如、齐夏、郑伟和李佳

长非编码 RNA (lncRNA) 已成为癌症进展的重要调节因子。唾液酸化异常会导致肾细胞癌 (RCC) 恶性肿瘤。然而,lncRNA母源表达基因3(MEG3)通过调节ST3Gal1转录和EGFR唾液酸化介导RCC进展的机制仍不清楚。在这里,我们发现MEG3在邻近组织中的表达高于 RCC 组织,并且与正常肾细胞中的表达相比,在 RCC 细胞系中表达下调。转染MEG3的RCC细胞的增殖、迁移和侵袭能力下降,而敲除MEG3则产生相反的效果。RCC细胞的体内增殖和转移能力与其体外行为一致。ST3Gal1在RCC中表达失调,并与MEG3呈正相关。通过应用生物信息学,c-Jun(也称为 JUN)被鉴定为预测结合ST3Gal1启动子的转录因子,并且MEG3水平的改变导致 c-Jun 表达的变化。此外,ST3Gal1 调节 EGFR 唾液酸化以抑制 EGFR 磷酸化,从而影响磷酸肌醇 3 激酶 (PI3K)-AKT 通路的激活。总而言之,我们的研究结果提供了一种新的机制来阐明MEG3 –ST3Gal1-EGFR 轴在 RCC 进展中的作用。

更新日期:2020-09-02
down
wechat
bug