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Updated: Mar 21, 2026
In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
A dual PI3K/AKT/mTOR signaling inhibitor miR-99a suppresses endometrial carcinoma
Yunyun Li1, Zhongzu Zhang2, Xiaojing Zhang1
1Department of Gynecology and Obstetrics, The Yongchuan Hospital of Chongqing Medical University Chongqing 402160, PR China.
Abstract:
Activation of the PI3K/AKT/mTOR signaling pathway, a common mechanism in all subtypes of endometrial cancers (EC), plays an important role in the initiation and progression of many cancers. Inhibitors against various components of this pathway might promise a novel effective approach for targeted therapy for EC in the future. Intriguingly, two major members of this pathway, AKT1 and mTOR, were both reported to be the putative target genes of miR-99a, which were widely reported to function as a tumor suppressor in a variety of cancers. However, the direct role of miR-99a in endometrial cancer progression and the signaling pathways might been involved have never been deciphered. In this paper, we demonstrate that the expression of miR-99a was significantly suppressed in the EC tissues and was negatively correlated with the differentiation of tumors. Furthermore, we find that overexpression of miR-99a in EC cells induced a complex phenotype, namely an inhibition of cell proliferation, block of G1/S phase transition, induction of cell apoptosis, suppression of cell invasion, and inhibition of tumor growth in vivo, which was mediated, at least partially, through dual-suppression of PI3K/AKT/mTOR pathway. This finding not only helps us understand the molecular mechanism of endometrial carcinogenesis, but also gives us a strong rationale to further investigate miR-99a as a potential biomarker and therapeutic target for EC.
Insights
MicroRNA-99a (miR-99a) acts as a tumor suppressor in endometrial cancer (EC). Its suppressed expression correlates with poor differentiation, and restoring miR-99a inhibits EC cell growth and invasion by targeting the PI3K/AKT/mTOR pathway.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- The PI3K/AKT/mTOR pathway is crucial in endometrial cancer (EC) initiation and progression.
- MicroRNAs (miRNAs) are key regulators of gene expression implicated in cancer.
- miR-99a is a known tumor suppressor in various cancers, potentially targeting AKT1 and mTOR.
Purpose of the Study:
- To investigate the role of miR-99a in endometrial cancer progression.
- To identify the signaling pathways regulated by miR-99a in EC.
- To explore miR-99a as a potential therapeutic target for EC.
Main Methods:
- Quantitative analysis of miR-99a expression in EC tissues.
- In vitro studies involving overexpression of miR-99a in EC cell lines.
- Assessment of cell proliferation, cell cycle, apoptosis, and invasion.
- In vivo tumor growth assays in mouse models.
- Western blot analysis to examine PI3K/AKT/mTOR pathway components.
Main Results:
- miR-99a expression is significantly suppressed in EC tissues and negatively correlated with tumor differentiation.
- Overexpression of miR-99a inhibits EC cell proliferation, induces apoptosis, and suppresses invasion.
- miR-99a overexpression blocks G1/S phase transition and reduces tumor growth in vivo.
- These effects are mediated, at least partially, by the dual suppression of the PI3K/AKT/mTOR pathway.
Conclusions:
- miR-99a functions as a tumor suppressor in endometrial cancer.
- Restoring miR-99a expression inhibits EC progression via the PI3K/AKT/mTOR pathway.
- miR-99a holds potential as a biomarker and therapeutic target for EC.
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