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Roles of microRNAs in Gastrointestinal Cancer Stem Cell Resistance and Therapeutic Development

Hwang, Ga-Ram, Yuen, John G., Ju, Jingfang·2021·International Journal of Molecular Sciences
DOI 10.3390/ijms22041624PMC PMC7915611
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Abstract

Resistance to cancer treatment is one of the major challenges currently faced when treating gastrointestinal (GI) cancers. A major contributing factor to this resistance is the presence of cancer stem cells (CSCs) in GI cancers (e.g., colorectal, pancreatic, gastric, liver cancer). Non-coding RNAs, such as microRNAs (miRNAs), have been found to regulate several key targets that are responsible for cancer stemness, and function as oncogenic miRNAs (oncomiRs) or tumor suppressor miRNAs. As a result, several miRNAs have been found to alter, or be altered by, the expression of CSC-defining markers and their related pathways. These miRNAs can be utilized to affect stemness in multiple ways, including directly targeting CSCs and enhancing the efficacy of cancer therapeutics. This review highlights current studies regarding the roles of miRNAs in GI CSCs, and efforts towards the development of cancer therapeutics.

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Figure 1 Modification of tumor suppressor miRNA with 5-FU as a novel miRNA-based therapeutic strategy. The guide strand of tumor suppressor miR-15a can be modified by replacing the uracils with a chemotherapeutic nucleoside analog, 5-FU (green), to make 5-FU-miR-15a. The passenger strand remains intact to minimize off-target effects. The 5-FU-miR-15a has several unique properties derived by integrating the therapeutic powers of miR-15a with 5-FU to impact multiple targets/pathways, such as stemness, apoptosis and cell cycle in CRC and PDAC (down arrows represent downregulated expression and up arrow represents increased effect). In addition, 5-FU-miR-15a can be delivered without the use of a delivery vehicle. This novel modification strategy can potentially be applied to other tumor suppressor miRNA candidates and cancer types.
Figure 1 Modification of tumor suppressor miRNA with 5-FU as a novel miRNA-based therapeutic strategy. The guide strand of tumor suppressor miR-15a can be modified by replacing the uracils with a chemotherapeutic nucleoside analog, 5-FU (green), to make 5-FU-miR-15a. The passenger strand remains intact to minimize off-target effects. The 5-FU-miR-15a has several unique properties derived by integrating the therapeutic powers of miR-15a with 5-FU to impact multiple targets/pathways, such as stemness, apoptosis and cell cycle in CRC and PDAC (down arrows represent downregulated expression and up arrow represents increased effect). In addition, 5-FU-miR-15a can be delivered without the use of a delivery vehicle. This novel modification strategy can potentially be applied to other tumor suppressor miRNA candidates and cancer types.CC BY · PubMed Central

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Metadata

Authors
Hwang, G.-R., Yuen, J. G., & Ju, J.
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2021-02-05
Volume
22
Issue
4
Pages
1624
ISSN
1422-0067
DOI
10.3390/ijms22041624
PMC
PMC7915611
Cited by
15
References
7
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
National Institutes of Health (R01CA15501904)

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CoChat. (2026). Citation check: Roles of microRNAs in Gastrointestinal Cancer Stem Cell Resistance and Therapeutic Development. https://app.cochat.ai/papers/10.3390/ijms22041624
The paper
Hwang, G.-R., Yuen, J. G., & Ju, J. (2021). Roles of microRNAs in Gastrointestinal Cancer Stem Cell Resistance and Therapeutic Development. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms22041624