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长链非编码 LEF1-AS1 通过 miR-5100/DEK/AMPK-mTOR 轴调控胃癌细胞凋亡和自噬。

Long Non-Coding LEF1-AS1 Sponge miR-5100 Regulates Apoptosis and Autophagy in Gastric Cancer Cells via the miR-5100/DEK/AMPK-mTOR Axis.

机构信息

Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan 430000, China.

出版信息

Int J Mol Sci. 2022 Apr 26;23(9):4787. doi: 10.3390/ijms23094787.

Abstract

DEK and miR-5100 play critical roles in many steps of cancer initiation and progression and are directly or indirectly regulated by most promoters and repressors. LEF1-AS1 as a long non-coding RNA can regulate tumor development through sponge miRNA. The effect and regulatory mechanism of DEK on autophagy and apoptosis in gastric cancer (GC), and the role between miR-5100 and DEK or miR-5100 and LEF1-AS1 are still unclear. Our study found that DEK was highly expressed in gastric cancer tissues and cell lines, and knockdown of DEK inhibited the autophagy of cells, promoted apoptosis, and suppressed the malignant phenotype of gastric cancer. DEK regulates autophagy and apoptosis through the AMPK/mTOR signaling pathway. In addition, miR-5100 inhibits autophagy and promotes apoptosis in GC cells while LEF1-AS1 had the opposite effect. Studies have shown that miR-5100 acts by targeting the 3'UTR of DEK, and LEF1-AS1 regulates the expression of miR-5100 by sponging with mIR-5100. In conclusion, our results found that LEF1-AS1 and miR-5100 sponge function, and the miR-5100/DEK/AMPK/mTOR axis regulates autophagy and apoptosis in gastric cancer cells.

摘要

DEK 和 miR-5100 在癌症的发生和发展的多个步骤中起着关键作用,并且直接或间接地受到大多数启动子和抑制子的调节。长链非编码 RNA LEF1-AS1 可以通过海绵 miRNA 来调节肿瘤的发生。DEK 在胃癌(GC)中对自噬和凋亡的作用及其调控机制,以及 miR-5100 与 DEK 或 miR-5100 与 LEF1-AS1 之间的关系尚不清楚。我们的研究发现,DEK 在胃癌组织和细胞系中高表达,敲低 DEK 抑制细胞自噬,促进细胞凋亡,抑制胃癌的恶性表型。DEK 通过 AMPK/mTOR 信号通路调节自噬和凋亡。此外,miR-5100 抑制 GC 细胞的自噬并促进凋亡,而 LEF1-AS1 则具有相反的作用。研究表明,miR-5100 通过靶向 DEK 的 3'UTR 发挥作用,而 LEF1-AS1 通过与 miR-5100 结合来调节其表达。总之,我们的研究结果发现,LEF1-AS1 和 miR-5100 具有海绵功能,miR-5100/DEK/AMPK/mTOR 轴调节胃癌细胞的自噬和凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35ad/9101949/78ad90637519/ijms-23-04787-g001.jpg

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