Downregulation of MicroRNA-152 contributes to high expression of DKK1 in multiple myeloma
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Updated: Apr 3, 2026
Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
Published on: April 6, 2012
Yinyin Xu1,2, Bingda Chen3,2, Suraj K George4
1a Department of Clinical Laboratory ; Affiliated Yongchuan Hospital of Chongqing Medical University ; Chongqing , PR China.
Abstract:
Multiple myeloma (MM) induced bone lesion is one of the most crippling characteristics, and the MM secreted Dickkopf-1 (DKK1) has been reported to play important role in this pathologic process. However, the underlying regulation mechanisms involved in DKK1 expression are still unclear. In this study, we validated the expression patterns of microRNA (miR) 15a, 34a, 152, and 223 in MM cells and identified that miR-152 was significantly downregulated in the MM group compared with the non-MM group, and that miR-152 level was negatively correlated with the expression of DKK1 in the MM cells. Mechanistic studies showed that manipulating miR-152 artificially in MM cells led to changes in DKK-1 expression, and miR-152 blocked DKK1 transcriptional activity by binding to the 3'UTR of DKK1 mRNA. Importantly, we revealed that MM cells stably expressing miR-152 improved the chemotherapy sensitivity, and counteracted the bone disruption in an intrabone-MM mouse model. Our study contributes better understanding of the regulation mechanism of DKK-1 in MM, and opens up the potential for developing newer therapeutic strategies in the MM treatment.
Insights
MicroRNA-152 (miR-152) is downregulated in multiple myeloma (MM) and targets Dickkopf-1 (DKK1). Restoring miR-152 enhances chemotherapy sensitivity and reduces bone lesions in MM mouse models.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Multiple myeloma (MM) causes debilitating bone lesions.
- Dickkopf-1 (DKK1) secreted by MM cells contributes to bone pathology.
- Mechanisms regulating DKK1 expression in MM remain largely unknown.
Purpose of the Study:
- To investigate the role of specific microRNAs (miRNAs) in regulating DKK1 expression in MM.
- To explore the therapeutic potential of targeting miRNA-DKK1 interactions in MM bone disease.
Main Methods:
- Expression analysis of miR-15a, miR-34a, miR-152, and miR-223 in MM cells.
- Correlation analysis between miR-152 levels and DKK1 expression.
- Functional studies involving artificial manipulation of miR-152 in MM cells.
- Assessment of miR-152 effects on DKK1 mRNA 3'UTR activity.
- Evaluation of miR-152 impact on chemotherapy sensitivity and bone disruption in an in vivo MM mouse model.
Main Results:
- miR-152 was significantly downregulated in MM cells compared to non-MM cells.
- miR-152 expression showed a negative correlation with DKK1 levels in MM cells.
- miR-152 directly targeted DKK1 mRNA, inhibiting its transcriptional activity.
- Overexpression of miR-152 in MM cells improved chemotherapy sensitivity.
- Stable expression of miR-152 counteracted bone disruption in an intrabone-MM mouse model.
Conclusions:
- miR-152 functions as a tumor suppressor by downregulating DKK1 in MM.
- Restoring miR-152 levels presents a potential therapeutic strategy for MM bone disease.
- This study elucidates a novel regulatory pathway for DKK1 in MM, offering new treatment avenues.
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