The Role and Function of microRNA in the Pathogenesis of Multiple Myeloma
Abstract
:1. Introduction
2. What Is miRNA?
3. Mechanisms of miRNA Production and Action
4. Cancer and miRNAs
5. miRNA Abnormalities in MM
6. Chromosomal Abnormalities and miRNA Expression in MM
7. miRNA and the p53 Pathway
8. Epigenetic Regulation and miRNA in MM
9. Other miRNA Regulatory Mechanisms in MM
10. Drug Resistance and miRNA
11. Possible Classification of MM by miRNA Expression Profiling
12. Circulating miRNA in the Bloodstream
13. miRNA and the Microenvironment
14. Potential Therapies Using miRNA
15. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Cytogenetic Group | Deregulated miRNA | Chromosomal Location | miRNA Target | Ref. |
---|---|---|---|---|
t(4;14) | miR-133b | 6p12.2 | FSCN1 | [29] |
miR-135b | 1q32.1 | |||
miR-146a | 5q34 | IRAK1, Fas, SMAD4, TBP, CCL8/MCP2 | ||
miR-155 | 21q21.3 | KPC1, IL-13Rα1, CYR61, SMAD1, SMAD2, SMAD5, HIVEP2, CEBPB, RUNX2, MYO10, JARID2, AGTR1 | ||
miR-193a | 17q11.2 | |||
miR-196b | 7p15.2 | |||
miR-203 | 14q32.33 | P63, SOCS-3 | ||
miR-215 | 1q41 | DHFR, TS | ||
miR-342 | 14q32.2 | |||
miR-375 | 2q35 | YAP, RASD1, PDK1, 14-3-3Zeta | ||
miR-650 | 22q11.22 | NDRG2, ING4 | ||
t(11;14) | miR-95 | 4p16.1 | SNX1 | [29] |
miR-125a | 19q13.41 | PDPN, BAK1, KLF13, preproET1, ARID3B, HuR, ERBB2, ERBB3 | ||
miR-184 | 15q25.1 | AKT2 | ||
miR-199a | 19p13.2/1q24.3 | CD44, mTOR, c-MET, HIF1-α | ||
miR-215 | 1q41 | DHFR, TS | ||
miR-375 | 2q35 | YAP, RASD1, PDK1, 14-3-3Zeta | ||
miR-650 | 22q13.41 | NDRG2, ING4 | ||
t(14;16) | miR-1 | 20q13.33 | TAGLN2, KLF4, c-MET | [25,29] |
miR-99b | 19q13.41 | |||
miR-125a-5p | 19q13.42 | PDPN, BAK1, KLF13, preproET1, ARID3B, HuR, ERBB2, ERBB3 | ||
miR-133a | 18q11.2/20q13.33 | |||
miR-135b | 1q32.1 | |||
miR-196b | 7p15.2 | |||
miR-214 | 1q24.3 | PTEN | ||
miR-375 | 2p35 | YAP, RASD1, PDK1, 14-3-3Zeta | ||
miR-642 | 19q13.32 | |||
Deletion 13q14 | miR-15a-16 | 13q14.3 | E2F, CCND1, WNT3A, BCL-2 | [16,27] |
miR-181a/b | 1q32.1/9q33.3 | RASSF1A, TIMP3, NLK, Prox1, HOXA11 | ||
miR-221 | Xp11.3 | p27, ETS1, PUMA, p57, TIMP3, PTEN | ||
miR-222 | Xp11.3 | p27, PUMA, p57, TIMP3, PETN | ||
miR-382 | 14q32.31 | SOD2, NPM1, PSPC1, HSPD1, ECH1 | ||
1q gain | miR-205 | 1q32.2 | [25] | |
miR-215 | 1q41 | MDM2, RUNX1 | ||
miR-488 | 1q25.2 | |||
miR-1231 | 1q32.1 | |||
Deletion 17p | miR-22 | 17p13.3 | [25,29] | |
miR-324-5p | 17p13.1 | MDR, MRP, BCRP, BCL-2 family | [31] |
miRNA | Observed Alteration | Target | Functional Response | Ref |
---|---|---|---|---|
15a/16 | Downregulated | NA | IL-6 downregulates miR-15a/16 and enhances drug resistance | [72] |
221/222 | Upregulated in melphalan-resistant HMCLs | PUMA/BBC3 | miR-221/222 inhibitor upregulates PUMA, increasing apoptosis in drug-resistant HMCLs | [20,21] |
221/222 | Upregulated in DEX-resistant HMCL (MM.1R) | PUMA/BBC3 | Inhibition of miR-221/222 in MM.1R cells partially restores their DEX sensitivity, whereas enforced expression in MM.1S cells downregulates PUMA and renders them resistant to DEX | [22] |
125a | Upregulated in MM cells following adhesion to BMSCs | p53 | NA | [39] |
125b | Upregulated in DEX-responsive MM cells | p53, interacts with miR-34a targeting SIRT1 | Anti-miR-125b increases p53, miR-34a, decreased SIRT1, and increases DEX-induced apoptosis | [42] |
137 | Downregulated in MM cells harboring 1p12-21 deletion | MCL-1, AKT, AURKA | Targets MCL1, AURKA, and AKT; Ectopic expression of miR-137 sensitizes cells to bortezomib via upregulating p53 and downregulating ATM/Chk2 | [73,74,75] |
27a | Downregulated in BTZ-resistant HMCLs | CDK5 | Ectopic expression of miR-27a in MM cells increases their sensitivity to BTZ | [76] |
631 | Downregulated in BTZ-resistant HMCL | UbcH10/MDR1 | Modulates UbcH10/MDR1 pathway, which is associated with BTZ resistance in HMCL | [77] |
324-5p | Located on 17p and downregulated in MM cells harboring 17p deletion | BCL2 family gene and MDR1, BCRP, MRP | Regulates sensitivity to bortezomib in MM cells by targeting hedgehog signaling | [31] |
155 | Downregulated in MM cells | PSMβ5 | miR-155 elicits anti-MM activity likely via proteasome inhibition | [78] |
497 | Downregulated in MM cells | BCL-2 | miR-497 suppresses MM cell proliferation and promotes apoptosis by directly targeting BCL-2 and increases the sensitivity of MM cells to bortezomib | [79] |
520g/520h | Downregulated in BTZ-resistant HMCL | APE1 | Combined overexpression of miR-520g and miR-520h overcomes bortezomib resistance in MM through inhibition of DNA repair | [80] |
21 | Upregulated in MM cells following adhesion to BMSCs | RhoB | Enforced expression of miR-21 leads to reduced apoptosis induced by DEX, DOX, and BTZ; inhibition of this miRNA induces the opposite effects | [81] |
21 | Upregulated in melphalan-resistant HMCLs | NA | NA | [19] |
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Handa, H.; Murakami, Y.; Ishihara, R.; Kimura-Masuda, K.; Masuda, Y. The Role and Function of microRNA in the Pathogenesis of Multiple Myeloma. Cancers 2019, 11, 1738. https://doi.org/10.3390/cancers11111738
Handa H, Murakami Y, Ishihara R, Kimura-Masuda K, Masuda Y. The Role and Function of microRNA in the Pathogenesis of Multiple Myeloma. Cancers. 2019; 11(11):1738. https://doi.org/10.3390/cancers11111738
Chicago/Turabian StyleHanda, Hiroshi, Yuki Murakami, Rei Ishihara, Kei Kimura-Masuda, and Yuta Masuda. 2019. "The Role and Function of microRNA in the Pathogenesis of Multiple Myeloma" Cancers 11, no. 11: 1738. https://doi.org/10.3390/cancers11111738
APA StyleHanda, H., Murakami, Y., Ishihara, R., Kimura-Masuda, K., & Masuda, Y. (2019). The Role and Function of microRNA in the Pathogenesis of Multiple Myeloma. Cancers, 11(11), 1738. https://doi.org/10.3390/cancers11111738