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Published on: February 21, 2014
Emerging roles of microRNAs in regulating the mTOR signaling pathway during tumorigenesis
Hossein Javid1,2, Arash Soltani1,2, Fariba Mohammadi1,2
1Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Abstract:
The mammalian target of rapamycin (mTOR) is a large Ser/Thr protein kinase that belongs to the phosphoinositide 3-kinase (PI3K) family and mediates various physiological and pathological processes, especially cell proliferation, protein synthesis, autophagy, and cancer development. The mTOR expression is transient and tightly regulated in normal cells, but it is overactivated in cancer cells. Recently, several studies have indicated that microRNAs (miRNAs) play a critical role in the regulation of mTOR and mTOR-associated processes, some acting as inhibitors and the others as activators. Although it is still in infancy, the strategy of combining both miRNAs and mTOR inhibitors might provide an approach to selectively sensitizing tumor cells to chemotherapy-induced DNA damage and subsequently attenuating the tumor cell growth and apoptosis.
Insights
MicroRNAs (miRNAs) regulate the mammalian target of rapamycin (mTOR) pathway, which is crucial in cell growth and cancer. Combining miRNAs and mTOR inhibitors may enhance cancer therapy by increasing tumor cell sensitivity to chemotherapy.
Area of Science:
- Molecular Biology
- Biochemistry
- Oncology
Background:
- The mammalian target of rapamycin (mTOR) is a key protein kinase involved in cell proliferation, protein synthesis, and autophagy.
- mTOR signaling is dysregulated in cancer, with overactivation observed in tumor cells compared to normal cells.
- MicroRNAs (miRNAs) are emerging as critical regulators of mTOR pathway activity, acting as both inhibitors and activators.
Purpose of the Study:
- To investigate the role of microRNAs (miRNAs) in regulating the mammalian target of rapamycin (mTOR) pathway.
- To explore the potential of combining miRNA-based strategies with mTOR inhibitors for cancer treatment.
Main Methods:
- Review of recent studies on miRNA-mTOR interactions.
- Analysis of miRNA and mTOR expression patterns in cancer.
- Exploration of therapeutic strategies involving miRNAs and mTOR inhibitors.
Main Results:
- miRNAs significantly influence mTOR activity and associated cellular processes.
- Dysregulation of specific miRNAs contributes to mTOR overactivation in cancer.
- Combination therapy with miRNAs and mTOR inhibitors shows promise in preclinical studies.
Conclusions:
- miRNAs are vital regulators of the mTOR pathway in both normal physiology and cancer.
- Targeting miRNAs alongside mTOR inhibitors offers a novel therapeutic avenue for cancer treatment.
- This combined approach may enhance chemotherapy efficacy by sensitizing tumor cells to DNA damage and promoting apoptosis.
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