Abstract |
MicroRNAs ( miRNA) have rapidly emerged as modulators of gene expression in cancer in which they may have great diagnostic and therapeutic import. MicroRNA-199a-3p (miR-199a-3p) is downregulated in several human malignancies including hepatocellular carcinoma (HCC). Here, we show that miR-199a-3p targets mammalian target of rapamycin (mTOR) and c-Met in HCC cells. Restoring attenuated levels of miR-199a-3p in HCC cells led to G(1)-phase cell cycle arrest, reduced invasive capability, enhanced susceptibility to hypoxia, and increased sensitivity to doxorubicin-induced apoptosis. These in vitro findings were confirmed by an analysis of human HCC tissues, which revealed an inverse correlation linking miR-199a-3p and mTOR as well as a shorter time to recurrence after HCC resection in patients with lower miR-199a-3p expression. These results suggest that tactics to regulate mTOR and c-Met by elevating levels of miR-199a-3p may have therapeutic benefits in highly lethal cancers such as HCC.
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Authors | Francesca Fornari, Maddalena Milazzo, Pasquale Chieco, Massimo Negrini, George Adrian Calin, Gian Luca Grazi, Daniela Pollutri, Carlo Maria Croce, Luigi Bolondi, Laura Gramantieri |
Journal | Cancer research
(Cancer Res)
Vol. 70
Issue 12
Pg. 5184-93
(Jun 15 2010)
ISSN: 1538-7445 [Electronic] United States |
PMID | 20501828
(Publication Type: Journal Article)
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Chemical References |
- Antibiotics, Antineoplastic
- Intracellular Signaling Peptides and Proteins
- MicroRNAs
- RNA, Messenger
- mirn199 microRNA, human
- Doxorubicin
- Luciferases
- MTOR protein, human
- Proto-Oncogene Proteins c-met
- Protein Serine-Threonine Kinases
- TOR Serine-Threonine Kinases
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Topics |
- Aged
- Aged, 80 and over
- Antibiotics, Antineoplastic
(pharmacology)
- Apoptosis
(drug effects)
- Blotting, Western
- Carcinoma, Hepatocellular
(drug therapy, genetics, pathology)
- Cell Adhesion
(drug effects)
- Cell Cycle
(drug effects)
- Cell Movement
(drug effects)
- Cell Proliferation
(drug effects)
- Doxorubicin
(pharmacology)
- Drug Resistance, Neoplasm
- Female
- Gene Expression Regulation, Neoplastic
- Humans
- Intracellular Signaling Peptides and Proteins
(genetics, metabolism)
- Liver Cirrhosis
(drug therapy, genetics, pathology)
- Liver Neoplasms
(drug therapy, genetics, pathology)
- Luciferases
(metabolism)
- Male
- MicroRNAs
(physiology)
- Middle Aged
- Protein Serine-Threonine Kinases
(genetics, metabolism)
- Proto-Oncogene Proteins c-met
(genetics, metabolism)
- RNA, Messenger
(genetics, metabolism)
- Reverse Transcriptase Polymerase Chain Reaction
- TOR Serine-Threonine Kinases
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