The Roles of the Let-7 Family of MicroRNAs in the Regulation of Cancer Stemness.
The Roles of the Let-7 Family of MicroRNAs in the Regulation of Cancer Stemness.
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Let-7家族MicroRNAs在肿瘤干细胞调控中的作用
作者：
Ma Y;Shen N;Wicha MS;Luo M
长期以来，癌症一直被视为一种正常发育出现问题的疾病。肿瘤干细胞（Cancer stem-样细胞，CSCs），也被称为肿瘤起始细胞（tumor- initiation cells, tic），被越来越多地认为是一个关键的肿瘤细胞群，它不仅驱动肿瘤发生，还驱动癌症进展、治疗耐药性和转移性复发。let-7 microRNAs家族（miRNAs）首次在秀丽隐杆线虫中被发现，但在从蠕虫到人类的功能上保守，构成了从细胞增殖、分化和多能性到癌症发生和进展的多种细胞功能的重要调节因子。在这里，我们回顾了目前关于let-7 mirna在调节癌症干细胞中的作用的知识状态。我们概述了几个关键的rna结合蛋白，长链非编码rna （lncRNAs）和环状rna （circRNAs）参与调控let-7的生物发生、成熟和功能。然后，我们强调了由let-7 mirna家族调节或相互调节的关键基因靶点和信号通路，以调节各种类型癌症的CSC特征。我们还总结了现有证据表明，由let-7 mirna调节的不同代谢途径影响CSC自我更新、分化和治疗抗性。最后，我们回顾了目前的临床前研究，并讨论了开发基于let-7的替代策略作为潜在的癌症治疗方法的临床意义，这些策略可以通过不同的平台靶向CSCs，并在单独应用或与当前的化疗/放疗或分子靶向治疗联合使用时减少/克服治疗耐药性。通过特异性靶向CSCs，这些策略有可能显著提高癌症治疗的疗效。
Cancer has long been viewed as a disease of normal development gone awry. Cancer stem-like cells (CSCs), also termed as tumor-initiating cells (TICs), are increasingly recognized as a critical tumor cell population that drives not only tumorigenesis but also cancer progression, treatment resistance and metastatic relapse. The let-7 family of microRNAs (miRNAs), first identified in C. elegans but functionally conserved from worms to human, constitutes an important class of regulators for diverse cellular functions ranging from cell proliferation, differentiation and pluripotency to cancer development and progression. Here, we review the current state of knowledge regarding the roles of let-7 miRNAs in regulating cancer stemness. We outline several key RNA-binding proteins, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) involved in the regulation of let-7 biogenesis, maturation and function. We then highlight key gene targets and signaling pathways that are regulated or mutually regulated by the let-7 family of miRNAs to modulate CSC characteristics in various types of cancer. We also summarize the existing evidence indicating distinct metabolic pathways regulated by the let-7 miRNAs to impact CSC self-renewal, differentiation and treatment resistance. Lastly, we review current preclinical studies and discuss the clinical implications for developing let-7-based replacement strategies as potential cancer therapeutics that can be delivered through different platforms to target CSCs and reduce/overcome treatment resistance when applied alone or in combination with current chemo/radiation or molecularly targeted therapies. By specifically targeting CSCs, these strategies have the potential to significantly improve the efficacy of cancer therapies.
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影响因子：
5.2
作者：
Appari M;Babu KR;Kaczorowski A;Gross W;Herr I
通讯作者：
Herr I
DOI：
10.1158/1541-7786.mcr-14-0363
发表时间：
2015-03
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Alam M;Ahmad R;Rajabi H;Kufe D
通讯作者：
Kufe D
影响因子：
16.1
作者：
Chen, Yunching;Gao, Dong-Yu;Huang, Leaf
通讯作者：
Huang, Leaf
DOI：
10.1158/1940-6207.capr-11-0299
发表时间：
2012-03
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Bao B;Wang Z;Ali S;Ahmad A;Azmi AS;Sarkar SH;Banerjee S;Kong D;Li Y;Thakur S;Sarkar FH
通讯作者：
Sarkar FH
影响因子：
64.8
作者：
Denli, AM;Tops, BBJ;Hannon, GJ
通讯作者：
Hannon, GJ