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LINE-1 Methylation Analysis in Mesenchymal Stem Cells Treated with Osteosarcoma-Derived Extracellular Vesicles
Published on: February 1, 2020
Profiling of Autophagy-Associated microRNAs in the Osteosarcoma Cell Line of U2OS
Harun Mutlu1, Serhat Mutlu2, Mehmet Bostancıklıoğlu3
1Department of Orthopedics, Taksim Education and Research Hospital, Istanbul, Turkey.
Background:
Autophagy is a cellular process that plays a role in the destruction of proteins and organelles. It has been shown that impaired autophagic flux triggers canceration, infectious disease, and neurodegenerative diseases. It has been suggested that tumor formation is inhibited by autophagy that reduces oxidative stress and recycles damaged organelles. microRNAs are 17-25 bp in length, single-stranded, and noncoding small RNAs that play roles in the regulation of metabolic gene expression at the post-transcriptional level. Osteosarcoma is an aggressive bone cancer that affects mainly children and adolescents.
Objective:
The current article aims to profile autophagy-associated miRNAs in osteosarcoma cell lines and to examine the therapeutical potentials of these miRNAs by suppressing their expressions with Adriamycin and Rapamycin.
Methods:
We used fluidigm dynamic array nanofluidic chip 96.96 for mRNA expression assay in osteosarcoma cell line U2OS.
Results:
It was probed that after the suppression of autophagy-associated miRNAs by adriamycin and rapamycin, while most of the miRNAs were down-regulated in osteosarcoma cell lines, some miRNAs' expressions, such as miR-3141, miR-4296, miR-133b, and miR-720, were strikingly increased. Rapamycin and adriamycin, mTOR inhibitors, stir autophagic machinery, which results in decreased cell survival.
Conclusion:
Together, we propose that the expressions of miR-3141, miR-4296, miR-133b, and miR-720 might exacerbate the pathogenesis of osteosarcoma; therefore, the suppression of these miRNAs with the loss-offunction approaches could be an appropriate strategy that is worth testing in osteosarcoma.
Insights
Autophagy-associated microRNAs (miRNAs) were profiled in osteosarcoma. Certain miRNAs, including miR-3141 and miR-4296, were upregulated, suggesting they may promote osteosarcoma progression.
Area of Science:
- Cell Biology
- Molecular Oncology
- Biochemistry
Background:
- Autophagy is a cellular degradation process crucial for preventing diseases like cancer.
- Dysfunctional autophagy is linked to cancer, infectious, and neurodegenerative diseases.
- MicroRNAs (miRNAs) are small noncoding RNAs regulating gene expression post-transcriptionally.
Purpose of the Study:
- To profile autophagy-associated miRNAs in osteosarcoma cell lines.
- To investigate the therapeutic potential of targeting these miRNAs.
- To examine the effects of Adriamycin and Rapamycin on miRNA expression in osteosarcoma.
Main Methods:
- Utilized a fluidigm dynamic array nanofluidic chip for mRNA expression assays.
- Osteosarcoma cell line U2OS was used for experiments.
- Adriamycin and Rapamycin were employed to suppress miRNA expressions.
Main Results:
- Most autophagy-associated miRNAs were downregulated after treatment with Adriamycin and Rapamycin.
- Expressions of miR-3141, miR-4296, miR-133b, and miR-720 were significantly increased.
- Adriamycin and Rapamycin, as mTOR inhibitors, activate autophagy, leading to reduced cell survival.
Conclusions:
- Upregulated miR-3141, miR-4296, miR-133b, and miR-720 may contribute to osteosarcoma pathogenesis.
- Targeting these specific miRNAs through loss-of-function approaches could be a viable therapeutic strategy.
- Further investigation into miRNA suppression for osteosarcoma treatment is warranted.
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