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Updated: Jun 22, 2025

Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
Published on: April 6, 2012
MicroRNA-138 promotes the progression of multiple myeloma through targeting paired PAX5
Xiao Yan1, Keting Wang2, Cong Shi3
1Department of Haematology, The First Affiliated Hospital of Ningbo University, China; Ningbo Clinical Research Center for Hematologic malignancies, China.
Background:
Multiple myeloma cancer stem cells (MMSC) have been considered as the leading cause of multiple myeloma (MM) drug resistance and eventual relapse, microRNAs (miRNAs) collectively participate in the progression of MM. However, the pathogenesis of miR-138 in MMSC is still not fully understood.
Objective:
The intention of this study was to investigate the mechanism and role of miR-138 in multiple myeloma.
Method:
Bone marrow samples and peripheral blood from patients and normal controls were collected. Use Magnet-based Cancer Stem Cell Isolation Kit to separate and extract MMSC. Real-time quantitative PCR (RT-qPCR) was carried out to determine mRNA level. Western blot was applied to detect protein levels. MTT and flow cytometry were conducted to examine the proliferation and apoptosis of MMSC. Finally, dual-luciferase reporter gene assays were performed to confirm that paired box 5 (PAX5) is a direct target for miR-138.
Results:
Compared with normal group, the expression of miR-138 in patients was significantly up-regulated, and the expression of miR-138 was in a negative correlation with PAX5. Additionally, downregulated miR-138 facilitated the apoptosis and inhibited the proliferation of MMSC in vitro and in vivo. Downregulated miR-138 moderated the expression of PAX5, Bcl-2, Bax, and Caspase-3. PAX5 was a direct target of miR-138.
Conclusion:
Taken together, miR-138 plays a carcinogenic role in MM, and miR-138 adjusted the proliferation and apoptosis of MMSC by targeting PAX5. miR-138 has the probability of becoming a new medicinal target for the treatment of MM.
Insights
MicroRNA-138 (miR-138) promotes multiple myeloma (MM) progression and drug resistance by targeting PAX5. Downregulating miR-138 may offer a new therapeutic strategy for MM patients.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Multiple myeloma cancer stem cells (MMSC) drive drug resistance and relapse in multiple myeloma (MM).
- MicroRNAs (miRNAs) are implicated in MM progression, but the role of miR-138 in MMSC remains unclear.
Purpose of the Study:
- To investigate the mechanism and role of miR-138 in multiple myeloma.
Main Methods:
- Collected bone marrow and peripheral blood samples.
- Isolated MMSC using a Magnet-based Cancer Stem Cell Isolation Kit.
- Quantified gene and protein expression via RT-qPCR and Western blot.
- Assessed MMSC proliferation and apoptosis using MTT and flow cytometry.
- Confirmed PAX5 as a direct miR-138 target using dual-luciferase reporter assays.
Main Results:
- miR-138 expression was significantly upregulated in MM patients compared to controls.
- miR-138 expression negatively correlated with PAX5 expression.
- Downregulation of miR-138 inhibited MMSC proliferation and promoted apoptosis in vitro and in vivo.
- miR-138 regulated PAX5, Bcl-2, Bax, and Caspase-3 expression.
Conclusions:
- miR-138 acts as an oncomiR in MM, promoting MMSC proliferation and survival by targeting PAX5.
- miR-138 represents a potential therapeutic target for multiple myeloma treatment.
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