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Updated: Jul 5, 2026

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
Oncogenic role of miR-17-92 cluster in anaplastic thyroid cancer cells
Shu Takakura1, Norisato Mitsutake, Masahiro Nakashima
1Department of Molecular Medicine, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
Abstract:
Micro RNAs (miRNAs) are non-coding small RNAs and constitute a novel class of negative gene regulators that are found in both plants and animals. Several miRNAs play crucial roles in cancer cell growth. To identify miRNAs specifically deregulated in anaplastic thyroid cancer (ATC) cells, we performed a comprehensive analysis of miRNA expressions in ARO cells and primary thyrocytes using miRNA microarrays. MiRNAs in a miR-17-92 cluster were overexpressed in ARO cells. We confirmed the overexpression of those miRNAs by Northern blot analysis in ARO and FRO cells. In 3 of 6 clinical ATC samples, miR-17-3p and miR-17-5p were robustly overexpressed in cancer lesions compared to adjacent normal tissue. To investigate the functional role of these miRNAs in ATC cells, ARO and FRO cells were transfected with miRNA inhibitors, antisense oligonucleotides containing locked nucleic acids. Suppression of miR-17-3p caused complete growth arrest, presumably due to caspase activation resulting in apoptosis. MiR-17-5p or miR-19a inhibitor also induced strong growth reduction, but only miR-17-5p inhibitor led to cellular senescence. On the other hand, miR-18a inhibitor only moderately attenuated the cell growth. Thus, we have clarified functional differences among the members of the cluster in ATC cells. In conclusion, these findings suggest that the miR-17-92 cluster plays an important role in certain types of ATCs and could be a novel target for ATC treatment.
Insights
MicroRNAs (miRNAs) regulate genes and are crucial in cancer. This study found the miR-17-92 cluster is overexpressed in anaplastic thyroid cancer (ATC), with specific miRNAs inhibiting cancer cell growth and offering potential therapeutic targets.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- Micro RNAs (miRNAs) are small non-coding RNAs that function as negative gene regulators in plants and animals.
- Dysregulation of specific miRNAs is implicated in the progression of various cancers, including anaplastic thyroid cancer (ATC).
Purpose of the Study:
- To identify specific microRNAs (miRNAs) deregulated in anaplastic thyroid cancer (ATC) cells.
- To investigate the functional roles of the overexpressed miR-17-92 cluster members in ATC cell proliferation and survival.
Main Methods:
- Comprehensive analysis of miRNA expression profiles in ATC cell lines (ARO, FRO) and primary thyrocytes using miRNA microarrays.
- Confirmation of miRNA overexpression via Northern blot analysis.
- Functional studies involving transfection with miRNA inhibitors (locked nucleic acid antisense oligonucleotides) to assess effects on cell growth, apoptosis, and senescence.
Main Results:
- The miR-17-92 cluster was found to be significantly overexpressed in ATC cells compared to normal thyrocytes.
- In clinical ATC samples, miR-17-3p and miR-17-5p showed robust overexpression in cancer tissues.
- Inhibition of miR-17-3p induced complete growth arrest via apoptosis, while miR-17-5p inhibition led to growth reduction and cellular senescence, highlighting distinct functional roles within the cluster.
Conclusions:
- The miR-17-92 cluster plays a critical role in the pathogenesis of certain anaplastic thyroid cancers.
- Specific miRNAs within the cluster, particularly miR-17-3p and miR-17-5p, exhibit potent anti-proliferative effects and represent potential therapeutic targets for ATC treatment.
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