The Roles of the Let-7 Family of MicroRNAs in the Regulation of Cancer Stemness
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...
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doaj-732aeb60d3254847abdb1ccdbad126ba2021-09-25T23:53:05ZengMDPI AGCells2073-44092021-09-01102415241510.3390/cells10092415The Roles of the Let-7 Family of MicroRNAs in the Regulation of Cancer StemnessYuxi Ma0Na Shen1Max S. Wicha2Ming Luo3Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI 48109, USADepartment of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI 48109, USADepartment of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI 48109, USADepartment of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI 48109, USACancer 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.https://www.mdpi.com/2073-4409/10/9/2415cancer stem cells (CSCs)tumor suppressor microRNAslong non-coding RNAs (lncRNAs)circular RNAs (circRNAs)lin28glucose metabolism |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yuxi Ma Na Shen Max S. Wicha Ming Luo |
spellingShingle |
Yuxi Ma Na Shen Max S. Wicha Ming Luo The Roles of the Let-7 Family of MicroRNAs in the Regulation of Cancer Stemness Cells cancer stem cells (CSCs) tumor suppressor microRNAs long non-coding RNAs (lncRNAs) circular RNAs (circRNAs) lin28 glucose metabolism |
author_facet |
Yuxi Ma Na Shen Max S. Wicha Ming Luo |
author_sort |
Yuxi Ma |
title |
The Roles of the Let-7 Family of MicroRNAs in the Regulation of Cancer Stemness |
title_short |
The Roles of the Let-7 Family of MicroRNAs in the Regulation of Cancer Stemness |
title_full |
The Roles of the Let-7 Family of MicroRNAs in the Regulation of Cancer Stemness |
title_fullStr |
The Roles of the Let-7 Family of MicroRNAs in the Regulation of Cancer Stemness |
title_full_unstemmed |
The Roles of the Let-7 Family of MicroRNAs in the Regulation of Cancer Stemness |
title_sort |
roles of the let-7 family of micrornas in the regulation of cancer stemness |
publisher |
MDPI AG |
series |
Cells |
issn |
2073-4409 |
publishDate |
2021-09-01 |
description |
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. |
topic |
cancer stem cells (CSCs) tumor suppressor microRNAs long non-coding RNAs (lncRNAs) circular RNAs (circRNAs) lin28 glucose metabolism |
url |
https://www.mdpi.com/2073-4409/10/9/2415 |
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