MicroRNA Regulation of Cancer Stem Cells and Therapeutic Implications

Overview

Journal AAPS J

Specialty Pharmacology

Date 2009 Oct 21

PMID 19842044

Citations 71

Authors

Jeffrey T DeSano

Liang Xu

Affiliations

Soon will be listed here.

Abstract

MicroRNAs (miRNAs) are a class of endogenous non-protein-coding RNAs that function as important regulatory molecules by negatively regulating gene and protein expression via the RNA interference (RNAi) machinery. MiRNAs have been implicated to control a variety of cellular, physiological, and developmental processes. Aberrant expressions of miRNAs are connected to human diseases such as cancer. Cancer stem cells are a small subpopulation of cells identified in a variety of tumors that are capable of self-renewal and differentiation. Dysregulation of stem cell self-renewal is a likely requirement for the initiation and formation of cancer. Furthermore, cancer stem cells are a very likely cause of resistance to current cancer treatments, as well as relapse in cancer patients. Understanding the biology and pathways involved with cancer stem cells offers great promise for developing better cancer therapies, and might one day even provide a cure for cancer. Emerging evidence demonstrates that miRNAs are involved in cancer stem cell dysregulation. Recent studies also suggest that miRNAs play a critical role in carcinogenesis and oncogenesis by regulating cell proliferation and apoptosis as oncogenes or tumor suppressors, respectively. Therefore, molecularly targeted miRNA therapy could be a powerful tool to correct the cancer stem cell dysregulation.

Citing Articles

The Multifaceted Roles of MicroRNA-181 in Stem Cell Differentiation and Cancer Stem Cell Plasticity.

Yang C, Wang R, Hardy P Cells. 2025; 14(2.

PMID: 39851559 PMC: 11763446. DOI: 10.3390/cells14020132.

miR-3191 promotes the proliferation and metastasis of hepatocellular carcinoma via regulating PAK6.

Xie A, Wang H, Huang J, Sun M, Chen L Infect Agent Cancer. 2024; 19(1):64.

PMID: 39696440 PMC: 11654304. DOI: 10.1186/s13027-024-00628-w.

MicroRNA-206 as a promising epigenetic approach to modulate tumor-associated macrophages in hepatocellular carcinoma.

Ramoni D, Montecucco F World J Gastroenterol. 2024; 30(41):4503-4508.

PMID: 39534416 PMC: 11551670. DOI: 10.3748/wjg.v30.i41.4503.

MHESMMR: a multilevel model for predicting the regulation of miRNAs expression by small molecules.

Guan Y, Yu C, Li L, You Z, Wei M, Wang X BMC Bioinformatics. 2024; 25(1):6.

PMID: 38166644 PMC: 10763044. DOI: 10.1186/s12859-023-05629-x.

Cancer Stem Cells and Treatment of Cancer: An Update and Future Perspectives.

Khan M, Naeem M, Chaudary S, Ahmed A, Ahmed A Curr Stem Cell Res Ther. 2023; 19(10):1312-1320.

PMID: 37818567 DOI: 10.2174/011574888X247548230921063514.

References

Bussolati B, Grange C, Sapino A, Camussi G . Endothelial cell differentiation of human breast tumour stem/progenitor cells. J Cell Mol Med. 2008; 13(2):309-319. PMC: 3087118. DOI: 10.1111/j.1582-4934.2008.00338.x. View

Zhao R, Zhu Y, Shi Y . New hope for cancer treatment: exploring the distinction between normal adult stem cells and cancer stem cells. Pharmacol Ther. 2008; 119(1):74-82. DOI: 10.1016/j.pharmthera.2008.04.008. View

Szotek P, Pieretti-Vanmarcke R, Masiakos P, Dinulescu D, Connolly D, Foster R . Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsiveness. Proc Natl Acad Sci U S A. 2006; 103(30):11154-9. PMC: 1544057. DOI: 10.1073/pnas.0603672103. View

Xu L, Huang C, Huang W, Tang W, Rait A, Yin Y . Systemic tumor-targeted gene delivery by anti-transferrin receptor scFv-immunoliposomes. Mol Cancer Ther. 2002; 1(5):337-46. View

Cimmino A, Calin G, Fabbri M, Iorio M, Ferracin M, Shimizu M . miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A. 2005; 102(39):13944-9. PMC: 1236577. DOI: 10.1073/pnas.0506654102. View

Domen J, Cheshier S, Weissman I . The role of apoptosis in the regulation of hematopoietic stem cells: Overexpression of Bcl-2 increases both their number and repopulation potential. J Exp Med. 2000; 191(2):253-64. PMC: 2195763. DOI: 10.1084/jem.191.2.253. View

Hambardzumyan D, Becher O, Holland E . Cancer stem cells and survival pathways. Cell Cycle. 2008; 7(10):1371-8. DOI: 10.4161/cc.7.10.5954. View

Quintana E, Shackleton M, Sabel M, Fullen D, Johnson T, Morrison S . Efficient tumour formation by single human melanoma cells. Nature. 2008; 456(7222):593-8. PMC: 2597380. DOI: 10.1038/nature07567. View

Zhang M, Behbod F, Atkinson R, Landis M, Kittrell F, Edwards D . Identification of tumor-initiating cells in a p53-null mouse model of breast cancer. Cancer Res. 2008; 68(12):4674-82. PMC: 2459340. DOI: 10.1158/0008-5472.CAN-07-6353. View

10.

Zeng Y, Yi R, Cullen B . MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms. Proc Natl Acad Sci U S A. 2003; 100(17):9779-84. PMC: 187842. DOI: 10.1073/pnas.1630797100. View

11.

Jin L, Hope K, Zhai Q, Smadja-Joffe F, Dick J . Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat Med. 2006; 12(10):1167-74. DOI: 10.1038/nm1483. View

12.

Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C . let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell. 2007; 131(6):1109-23. DOI: 10.1016/j.cell.2007.10.054. View

13.

He X, He L, Hannon G . The guardian's little helper: microRNAs in the p53 tumor suppressor network. Cancer Res. 2007; 67(23):11099-101. DOI: 10.1158/0008-5472.CAN-07-2672. View

14.

Morrison S, Spradling A . Stem cells and niches: mechanisms that promote stem cell maintenance throughout life. Cell. 2008; 132(4):598-611. PMC: 4505728. DOI: 10.1016/j.cell.2008.01.038. View

15.

Zhang B, Pan X, Cobb G, Anderson T . microRNAs as oncogenes and tumor suppressors. Dev Biol. 2006; 302(1):1-12. DOI: 10.1016/j.ydbio.2006.08.028. View

16.

Uziel T, Karginov F, Xie S, Parker J, Wang Y, Gajjar A . The miR-17~92 cluster collaborates with the Sonic Hedgehog pathway in medulloblastoma. Proc Natl Acad Sci U S A. 2009; 106(8):2812-7. PMC: 2636735. DOI: 10.1073/pnas.0809579106. View

17.

Lawson D, Witte O . Stem cells in prostate cancer initiation and progression. J Clin Invest. 2007; 117(8):2044-50. PMC: 1934594. DOI: 10.1172/JCI32810. View

18.

Godlewski J, Nowicki M, Bronisz A, Williams S, Otsuki A, Nuovo G . Targeting of the Bmi-1 oncogene/stem cell renewal factor by microRNA-128 inhibits glioma proliferation and self-renewal. Cancer Res. 2008; 68(22):9125-30. DOI: 10.1158/0008-5472.CAN-08-2629. View

19.

Mayr C, Hemann M, Bartel D . Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation. Science. 2007; 315(5818):1576-9. PMC: 2556962. DOI: 10.1126/science.1137999. View

20.

Dick J . Normal and leukemic human stem cells assayed in SCID mice. Semin Immunol. 1996; 8(4):197-206. DOI: 10.1006/smim.1996.0025. View