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LIN28A/LIN28B与let-7环在人类恶性肿瘤中的异常调控及其对癌症特征的影响。

Aberrant regulation of the LIN28A/LIN28B and let-7 loop in human malignant tumors and its effects on the hallmarks of cancer.

作者信息

Wang Tianzhen, Wang Guangyu, Hao Dapeng, Liu Xi, Wang Dong, Ning Ning, Li Xiaobo

机构信息

Department of Pathology, Harbin Medical University, Harbin, China.

Department of Gastrointestinal Medical Oncology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.

出版信息

Mol Cancer. 2015 Jun 30;14:125. doi: 10.1186/s12943-015-0402-5.

Abstract

RNA binding proteins (RBPs) and microRNAs (miRNAs) are two of the most important post-transcriptional regulators of gene expression, and their aberrant expression contributes to the development of human malignancies. Let-7, one of the most well-known tumor suppressors, is frequently down-regulated in a variety of human cancers. The RBP LIN28A/LIN28B, a direct target of the let-7 family of miRNAs, is an inhibitor of let-7 biogenesis and is frequently up-regulated in cancers. Aberrant regulation of the LIN28A/LIN28B and let-7 loop in human malignant tumors is reportedly involved in cancer development, contributing to cellular proliferation, cell death resistance, angiogenesis, metastasis, metabolism reprogramming, tumor-associated inflammation, genome instability, acquiring immortality and evading immune destruction. In this review, we summarized the mechanisms of LIN28A/LIN28B and let-7 loop aberrant regulation in human cancer and discussed the roles and potential mechanisms of the LIN28A/LIN28B and let-7 loop in regulating the hallmarks of cancer. The crosstalk between LIN28A/LIN28B and let-7 loop and certain oncogenes (such as MYC, RAS, PI3K/AKT, NF-κB and β-catenin) in regulating hallmarks of cancer has also been discussed.

摘要

RNA结合蛋白(RBPs)和微小RNA(miRNAs)是基因表达最重要的两种转录后调节因子,它们的异常表达促进了人类恶性肿瘤的发展。Let-7是最著名的肿瘤抑制因子之一,在多种人类癌症中经常下调。RBP LIN28A/LIN28B是let-7家族miRNA的直接靶点,是let-7生物合成的抑制剂,在癌症中经常上调。据报道,人类恶性肿瘤中LIN28A/LIN28B和let-7环的异常调节与癌症发展有关,促进细胞增殖、细胞死亡抵抗、血管生成、转移、代谢重编程、肿瘤相关炎症、基因组不稳定、获得永生和逃避免疫破坏。在这篇综述中,我们总结了人类癌症中LIN28A/LIN28B和let-7环异常调节的机制,并讨论了LIN28A/LIN28B和let-7环在调节癌症特征中的作用和潜在机制。还讨论了LIN28A/LIN28B和let-7环与某些癌基因(如MYC、RAS、PI3K/AKT、NF-κB和β-连环蛋白)在调节癌症特征中的相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a45f/4512107/b9939802785b/12943_2015_402_Fig1_HTML.jpg

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