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微小 RNA 与胃癌中的 PTEN/PI3K/Akt 通路(综述)。

MicroRNAs and the PTEN/PI3K/Akt pathway in gastric cancer (Review).

机构信息

Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.

出版信息

Oncol Rep. 2019 Mar;41(3):1439-1454. doi: 10.3892/or.2019.6962. Epub 2019 Jan 10.

Abstract

Gastric carcinogenesis arises from complicated interactions among host, environmental and bacterial factors, which cause genetic and epigenetic dysregulation of oncogenic and tumor‑suppressive genes. MicroRNAs (miRNAs), a class of small non‑coding RNAs that post‑transcriptionally regulate ~30% human genes, may serve as oncogenes or tumor‑suppressors in malignancies, including gastric cancer (GC). Although miRNA dysregulation commonly exists in GC, exact roles miRNAs serve in the pathogenesis and promotion of this tumor remain undetermined. Recently, results of previous studies regarding mechanisms underlying miRNAs generally converged on pathways critical in cellular processes, including cell proliferation, apoptosis and invasion, among which phosphatase and tensin homolog (PTEN)/phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (Akt) signaling is a fundamental one, with frequent oncogenic alterations in GC. Therefore, in the present review, the disorder and function of miRNAs and PTEN/PI3K/Akt signaling in GC are discussed. Additionally, how miRNAs transduce their effects by regulating this pathway, particularly in GC stem cells and the tumor microenvironment, and two novel hypotheses significant in carcinogenesis, tumor progression and recurrence, are discussed. Furthermore, the roles of miRNAs and the PTEN/PI3K/Akt pathway in target therapies against this lethal disease are outlined.

摘要

胃癌的发生是宿主、环境和细菌因素之间复杂相互作用的结果,这些因素导致致癌和肿瘤抑制基因的遗传和表观遗传失调。微小 RNA(miRNA)是一类小的非编码 RNA,可在后转录水平调节约 30%的人类基因,可能在包括胃癌(GC)在内的恶性肿瘤中作为癌基因或肿瘤抑制因子发挥作用。尽管 miRNA 失调在 GC 中普遍存在,但 miRNA 在该肿瘤的发病机制和促进中的具体作用仍未确定。最近,先前关于 miRNA 作用机制的研究结果通常集中在细胞过程中关键的途径上,包括细胞增殖、凋亡和侵袭,其中磷酸酶和张力蛋白同源物(PTEN)/磷脂酰肌醇 3-激酶(PI3K)/蛋白激酶 B(Akt)信号通路是一个基本途径,在 GC 中经常发生致癌改变。因此,在本综述中,讨论了 miRNA 和 PTEN/PI3K/Akt 信号通路在 GC 中的失调和功能。此外,还讨论了 miRNA 如何通过调节该途径发挥其作用,特别是在 GC 干细胞和肿瘤微环境中,以及两个在致癌作用、肿瘤进展和复发中具有重要意义的新假说。此外,还概述了 miRNA 和 PTEN/PI3K/Akt 通路在针对这种致命疾病的靶向治疗中的作用。

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