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Repression of Multiple Myeloma Cell Growth In Vivo by Single-wall Carbon Nanotube SWCNT-delivered MALAT1 Antisense Oligos
Published on: December 13, 2018
miR-186 inhibits cell proliferation in multiple myeloma by repressing Jagged1
Zengyan Liu1, Guoqiang Zhang2, Wenzheng Yu3
1Department of Hematology, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan, Shandong 250012, China; Department of Hematology, Hospital Affiliated to Binzhou Medical University, 661 Second Huanghe Street, Binzhou 256603, China.
Abstract:
MicroRNAs (miRNAs) are small, noncoding ribonucleic acids that regulate gene expression by targeting mRNAs for translational repression and degradation. Accumulating experimental evidence supports a causal role of miRNAs in hematology tumorigenesis. However, the specific functions of miRNAs in the pathogenesis of multiple myeloma (MM) remain to be established. In this study, we demonstrated that miR-186 is commonly downregulated in MM cell lines and patient MM cells. Ectopic expression of miR-186 significantly inhibited cell growth, both in vitro and in vivo, and induced cell cycle G0/G1 arrest. Furthermore, miR-186 induced downregulation of Jagged1 protein expression by directly targeting its 3'-untranslated region (3'-UTR). Conversely, overexpression of Jagged1 rescued cells from miR-186-induced growth inhibition. Our collective results clearly indicate that miR-186 functions as a tumor suppressor in MM, supporting its potential as a therapeutic target for the disease.
Insights
MicroRNAs (miRNAs) are key regulators in cancer. This study shows miR-186 acts as a tumor suppressor in multiple myeloma (MM) by inhibiting cell growth and targeting Jagged1, offering a potential therapeutic target for MM.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- MicroRNAs (miRNAs) are small noncoding RNAs regulating gene expression.
- miRNAs play a role in hematologic malignancies.
- The function of miRNAs in multiple myeloma (MM) pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the role of miR-186 in multiple myeloma (MM).
- To identify the molecular targets and mechanisms of miR-186 in MM.
Main Methods:
- Assessed miR-186 expression in MM cell lines and patient samples.
- Performed in vitro and in vivo functional assays upon ectopic miR-186 expression.
- Identified Jagged1 as a direct target of miR-186 by 3'-UTR analysis.
Main Results:
- miR-186 was found to be downregulated in MM.
- Overexpression of miR-186 inhibited MM cell proliferation and induced G0/G1 cell cycle arrest.
- miR-186 directly targets Jagged1, and Jagged1 overexpression rescues MM cells from miR-186-mediated growth inhibition.
Conclusions:
- miR-186 functions as a tumor suppressor in multiple myeloma (MM).
- miR-186 warrants further investigation as a potential therapeutic target for MM.
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