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miRNAs 在结直肠癌发病机制和治疗耐药中的基石作用:信号通路相互作用的焦点——综述。

miRNAs as cornerstones in colorectal cancer pathogenesis and resistance to therapy: A spotlight on signaling pathways interplay - A review.

机构信息

Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt.

Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt.

出版信息

Int J Biol Macromol. 2022 Aug 1;214:583-600. doi: 10.1016/j.ijbiomac.2022.06.134. Epub 2022 Jun 26.

Abstract

Colorectal cancer (CRC) is the world's third most prevalent cancer and the main cause of cancer-related mortality. A lot of work has been put into improving CRC patients' clinical care, including the development of more effective methods and wide biomarkers variety for prognostic, and diagnostic purposes. MicroRNAs (miRNAs) regulate a variety of cellular processes and play a significant role in the CRC progression and spread via controlling their target gene expression by translation inhibition or mRNA degradation. Consequently, dysregulation and disruption in their function, miRNAs are linked to CRC malignant pathogenesis by controlling several cellular processes involved in the CRC. These cellular processes include increased proliferative and invasive capacity, cell cycle aberration, evasion of apoptosis, enhanced EMT, promotion of angiogenesis and metastasis, and decreased sensitivity to major treatments. The miRNAs control cellular processes in CRC via regulation of pathways such as Wnt/β-catenin signaling, PTEN/AKT/mTOR axis, KRAS, TGFb signaling, VEGFR, EGFR, and P53. Hence, the goal of this review was to review miRNA biogenesis and present an updated summary of oncogenic and tumor suppressor (TS) miRNAs and their potential implication in CRC pathogenesis and responses to chemotherapy and radiotherapy. We also summarise the biological importance and clinical applications of miRNAs in the CRC.

摘要

结直肠癌(CRC)是世界上第三大常见癌症,也是癌症相关死亡的主要原因。为了改善 CRC 患者的临床护理,已经做了很多工作,包括开发更有效的方法和广泛的生物标志物,以用于预后和诊断目的。微小 RNA(miRNA)调节多种细胞过程,并通过翻译抑制或 mRNA 降解来控制其靶基因的表达,从而在 CRC 的进展和扩散中发挥重要作用。因此,miRNA 的功能失调和破坏与 CRC 的恶性发病机制有关,通过控制涉及 CRC 的几个细胞过程来实现。这些细胞过程包括增殖和侵袭能力增加、细胞周期失常、逃避细胞凋亡、增强 EMT、促进血管生成和转移,以及对主要治疗方法的敏感性降低。miRNA 通过调节 Wnt/β-catenin 信号通路、PTEN/AKT/mTOR 轴、KRAS、TGFb 信号通路、VEGFR、EGFR 和 P53 等途径来控制 CRC 中的细胞过程。因此,本综述的目的是回顾 miRNA 的生物发生,并对致癌和肿瘤抑制(TS)miRNA 及其在 CRC 发病机制以及对化疗和放疗的反应中的潜在意义进行更新总结。我们还总结了 miRNA 在 CRC 中的生物学重要性和临床应用。

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