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Updated: Apr 7, 2026
In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
MiR-99a Inhibits Cell Proliferation and Tumorigenesis through Targeting mTOR in Human Anaplastic Thyroid Cancer
Hou-Gang Huang1, Xi Luo, Shuai Wu
1Department of Anaesthesiology, Yongchuan Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China
Abstract:
MicroRNAs (miRNAs) are emerging as critical regulators in carcinogenesis and tumor progression. Recently, miR-99a has been reported as a tumor suppressor gene in various human cancers, but its functions in the context of anaplastic thyroid cancer (ATC) remain unknown. In this study, we reported that miR-99a was commonly downregulated in ATC tissue specimens and cell lines with important functional consequences. Overexpression of miR-99a not only dramatically reduced ATC cell viability by inducing cell apoptosis and accumulation of cells at G1 phase, but also inhibited tumorigenicity in vivo. We then screened and identified a novel miR-99a target, mammalian target of rapamycin (mTOR), and it was further confirmed by luciferase assay. Up-regulation of miR-99a would markedly reduce the expression of mTOR and its downstream phosphorylated proteins (p-4E- BP1 and p-S6K1). Similar to restoring miR-99a expression, mTOR down-regulation suppressed cell viability and increased cell apoptosis, whereas restoration of mTOR expression significantly reversed the miR-99a antitumor activity and the inhibition of mTOR/p-4E-BP1/p-S6K1 signal pathway profile. In clinical specimens and cell lines, mTOR was commonly overexpressed and its protein levels were statistically inversely correlated with miR-99a expression. Taken together, our results demonstrated for the first time that miR-99a functions as a tumor suppressor and plays an important role in inhibiting the tumorigenesis through targeting the mTOR/p- 4E-BP1/p-S6K1 pathway in ATC cells. Given these, miR-99a may serve as a novel prognostic/diagnostic and therapeutic target for treating ATC.
Insights
MicroRNA 99a (miR-99a) acts as a tumor suppressor in anaplastic thyroid cancer (ATC) by inhibiting cell growth and targeting the mTOR pathway. Downregulation of miR-99a correlates with increased tumor progression, suggesting its therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are key regulators of gene expression involved in cancer development.
- miR-99a is recognized as a tumor suppressor in several cancers, but its role in anaplastic thyroid cancer (ATC) is uncharacterized.
- Anaplastic thyroid cancer (ATC) is an aggressive malignancy with limited therapeutic options.
Purpose of the Study:
- To investigate the function of miR-99a in anaplastic thyroid cancer (ATC).
- To identify the molecular targets of miR-99a in ATC.
- To explore the potential of miR-99a as a therapeutic target for ATC.
Main Methods:
- Analysis of miR-99a expression levels in ATC tissues and cell lines.
- Overexpression of miR-99a in ATC cells to assess its effects on cell viability, apoptosis, and cell cycle.
- In vivo tumorigenicity assays.
- Luciferase reporter assays to validate direct targeting of mammalian target of rapamycin (mTOR) by miR-99a.
- Western blot analysis to examine the expression of mTOR and its downstream signaling proteins (p-4E-BP1, p-S6K1).
Main Results:
- miR-99a was found to be significantly downregulated in ATC tissues and cell lines.
- Overexpression of miR-99a suppressed ATC cell viability, induced apoptosis, and caused G1 cell cycle arrest.
- miR-99a directly targets and downregulates mTOR expression, subsequently inhibiting the mTOR/p-4E-BP1/p-S6K1 signaling pathway.
- Downregulation of mTOR mimicked the tumor-suppressive effects of miR-99a, while mTOR restoration reversed these effects.
- mTOR was frequently overexpressed in ATC, with an inverse correlation between mTOR protein levels and miR-99a expression.
Conclusions:
- miR-99a functions as a tumor suppressor in anaplastic thyroid cancer (ATC).
- The tumor-suppressive role of miR-99a is mediated through the inhibition of the mTOR/p-4E-BP1/p-S6K1 signaling pathway.
- miR-99a represents a potential novel diagnostic, prognostic, and therapeutic target for ATC treatment.
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