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MAPK/ERK 信号通路与 MicroRNAs 的相互作用:调控癌细胞代谢和肿瘤进展的关键机制。

Interplay between MAPK/ERK signaling pathway and MicroRNAs: A crucial mechanism regulating cancer cell metabolism and tumor progression.

机构信息

Department of Biochemistry, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran.; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Life Sci. 2021 Aug 1;278:119499. doi: 10.1016/j.lfs.2021.119499. Epub 2021 Apr 15.

Abstract

Mitogen-activated protein kinase (MAPK) signal transduction, as a highly conserved signaling pathway, is reported to be involved in various biological events, including metabolic reprogramming, cell proliferation, survival, and differentiation. Mutations in key molecules involved in MAPK/ERK signaling and dysregulation of this pathway are very common events in various human malignancies, which make the MAPK signaling a crucial signaling pathway participating in the regulation of glucose uptake by malignant cells and tumorigenesis. MicroRNAs (miRNAs), as small non-coding RNAs, are critical regulators of gene expression that play key roles in cancer initiation and progression. On the other hand, these small RNAs mutually regulate the MAPK signaling which is often overexpressed in the case of cancer progression; suggesting that crosstalk between miRNAs and this signaling pathway plays a pivotal role in the development of human cancers. Some miRNAs such as miR-20b, miR-34c-3p, miR-152, miR-181a, and miR-302b through inhibiting MAPK signaling, and miR-193a-3p, miR-330-3p, and miR-592 by activating this signaling pathway, play imperative roles in tumorigenesis. Therefore, in this review, we aimed to focus on the interplay between miRNAs and MAPK signaling in the various steps of tumorigenesis, including metabolic regulation, cell proliferation, apoptosis, metastasis, angiogenesis, and drug resistance.

摘要

丝裂原活化蛋白激酶(MAPK)信号转导作为一种高度保守的信号通路,据报道参与了各种生物学事件,包括代谢重编程、细胞增殖、存活和分化。在 MAPK/ERK 信号转导中涉及的关键分子的突变以及该途径的失调是各种人类恶性肿瘤中非常常见的事件,这使得 MAPK 信号转导成为参与调节恶性细胞葡萄糖摄取和肿瘤发生的关键信号转导途径。微小 RNA(miRNA)作为小的非编码 RNA,是基因表达的关键调节剂,在癌症的发生和发展中起着关键作用。另一方面,这些小 RNA 相互调节 MAPK 信号转导,在癌症进展的情况下通常过度表达;这表明 miRNA 和该信号转导途径之间的串扰在人类癌症的发展中起着关键作用。一些 miRNA,如 miR-20b、miR-34c-3p、miR-152、miR-181a 和 miR-302b,通过抑制 MAPK 信号转导,miR-193a-3p、miR-330-3p 和 miR-592 通过激活该信号转导途径,在肿瘤发生中起着重要作用。因此,在这篇综述中,我们旨在重点关注 miRNA 和 MAPK 信号转导在肿瘤发生的各个步骤中的相互作用,包括代谢调节、细胞增殖、凋亡、转移、血管生成和耐药性。

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