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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-125b expression affects tumor growth of multiple myeloma via targeting MKK7
Yanxia Jiang1, Yajing Luan2, Dong He1
1Department of Hematology, The 1st Affiliated Hospital of Nanchang University Jiangxi, China.
Abstract:
Many miRNAs are reported to be involved in tumor development. The underlying mechanism of miRNAs driving multiple myeloma (MM) progress remains elusive. This study is to investigate the effect of miR-125b, a brain-enriched microRNA, on mitogen-activated protein kinase 7 (MKK7) in vivo. We found significantly up-regulation of miR-125b and deregulation of MKK7 in MM. The inverse correlation was further confirmed in multiple myeloma samples and cell lines. In addition, MKK7 was identified as a downstream target gene of miR-125b, which could bind to the 3' UTR of MKK7. Overexpression of miR-125b was associated with decreased MKK7 expression and miR-125b antagonisminhibited cell proliferation and clonogenicity. Taken together, our results demonstrated that MKK7 could function as an important tumor suppressor neutralized by miR-125b in MM, suggesting that miR-125b may be a novel potential molecular therapeutic target in the treatment of MM.
Insights
MicroRNAs (miRNAs) drive tumor development. This study shows miR-125b up-regulation in multiple myeloma (MM) suppresses tumor suppressor MKK7, indicating miR-125b as a potential therapeutic target for MM.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- MicroRNAs (miRNAs) play crucial roles in cancer development.
- The specific mechanisms by which miRNAs contribute to multiple myeloma (MM) progression are not fully understood.
Purpose of the Study:
- To investigate the role of miR-125b in multiple myeloma (MM).
- To determine the effect of miR-125b on mitogen-activated protein kinase 7 (MKK7) in MM.
Main Methods:
- Quantitative real-time PCR to measure miR-125b and MKK7 expression.
- Analysis of inverse correlation in MM patient samples and cell lines.
- Luciferase reporter assays to confirm MKK7 as a direct target of miR-125b.
- Assessment of cell proliferation and clonogenicity upon miR-125b manipulation.
Main Results:
- Significant up-regulation of miR-125b and deregulation of MKK7 observed in MM.
- Confirmed inverse correlation between miR-125b and MKK7 expression in MM.
- miR-125b directly targets MKK7 by binding to its 3' UTR.
- Overexpression of miR-125b decreased MKK7 expression and inhibited MM cell proliferation and clonogenicity.
Conclusions:
- MKK7 acts as a tumor suppressor in MM, and its function is inhibited by miR-125b.
- miR-125b neutralization of MKK7 contributes to MM progression.
- miR-125b represents a potential novel molecular therapeutic target for MM treatment.
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