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An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
miR-26b-5p suppresses proliferation and promotes apoptosis in multiple myeloma cells by targeting JAG1
Chui-Ming Jia1, Yu-Yang Tian1, Li-Na Quan1
1Hematology Department, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, China.
Background:
Though the levels of diagnosis and treatment of multiple myeloma (MM) have been largely improved recent years, the prognosis of these patients remain unacceptable. It is urgent for us to discover the exact mechanism and determine some new indicators for MM. MiRNAs play a critical role in the occurrence and progression of cancers, including MM. MiR-26b-5p has been reported to be closely related to cells proliferation in human pulmonary cancer, hepatocellular carcinoma and so on.
Material And Methods:
Here, we measured the expression of miR-26b-5p in MM samples and cell lines by real-time PCR. Then, Kaplan-Meier Curves were applied to assess the effect of miR-26b-5p expression on MM patients prognosis. Functionally, MTT assay and Flow cytometry were conducted to explore the functions of miR-26b-5p in cells proliferation and apoptosis. Furthermore, bioinformatics tools, Pearson's correlation coefficient analysis, gain-and loss of-function experiments and rescue experiment were used to determine the relationship between JAG1 and miR-26b-5p in MM cells. In addition, we also confirmed the role of JAG1 in MM cells proliferation and apoptosis by gain-and loss of-function experiments.
Results:
Here, we reported for the first time that miR-26b-5p was under-expressed in MM by real-time PCR. Clinically, Kaplan-Meier Curves showed that MM patients with lower miR-26b-5p expression had worse prognosis. Functionally, MTT assay revealed that miR-26b-5p inhibited cells proliferation. Flow cytometry indicated that miR-26b-5p accelerated tumor cells apoptosis. Furthermore, bioinformatics tools, Pearson's correlation coefficient analysis gain-and loss of-function experiments showed that JAG1 was the target of miR-26b-5p in MM cells. And, gain-and loss of-function experiments for JAG1 confirmed that JAG1 was an oncogene in MM cells. What's more, rescue experiment showed that JAG1 mediated the function of miR-26b-5p in MM cells.
Conclusion:
MiR-26b-5p acts as a tumor suppressor through suppressing cells proliferation and inducing cells apoptosis via directly targeting JAG1 in MM. MiR-26b-5p could be a potential and ponderable tumor target for MM in future.
Insights
MicroRNA-26b-5p is underexpressed in multiple myeloma (MM), correlating with poorer prognosis. This microRNA suppresses tumor growth and promotes apoptosis by targeting JAG1, presenting a potential therapeutic target for MM.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Multiple myeloma (MM) prognosis remains poor despite treatment advances.
- MicroRNAs (miRNAs) are crucial in cancer development, including MM.
- MiR-26b-5p is implicated in various cancers, suggesting a role in MM.
Purpose of the Study:
- Investigate miR-26b-5p expression in MM.
- Determine the prognostic value of miR-26b-5p in MM patients.
- Elucidate the functional role of miR-26b-5p and its target JAG1 in MM cell behavior.
Main Methods:
- Real-time PCR for miR-26b-5p expression analysis.
- Kaplan-Meier curves for survival analysis.
- MTT assays and flow cytometry for proliferation and apoptosis studies.
- Bioinformatics, correlation analysis, and gain/loss-of-function experiments to identify and validate JAG1 as a miR-26b-5p target.
Main Results:
- MiR-26b-5p was significantly underexpressed in MM tissues and cell lines.
- Lower miR-26b-5p levels correlated with worse patient prognosis.
- MiR-26b-5p inhibited MM cell proliferation and induced apoptosis.
- JAG1 was identified as a direct target of miR-26b-5p and functions as an oncogene in MM.
Conclusions:
- MiR-26b-5p acts as a tumor suppressor in MM by targeting JAG1.
- It inhibits proliferation and promotes apoptosis in MM cells.
- MiR-26b-5p represents a potential therapeutic target for multiple myeloma.
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