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MiR-199a-3p Regulates mTOR and c-Met to Influence the Doxorubicin Sensitivity of Human Hepatocarcinoma Cells
- Source :
- Cancer Research. 70:5184-5193
- Publication Year :
- 2010
- Publisher :
- American Association for Cancer Research (AACR), 2010.
-
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 G1-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. Cancer Res; 70(12); 5184–93. ©2010 AACR.
- Subjects :
- Liver Cirrhosis
Male
Cancer Research
Cell
Apoptosis
Protein-Serine-Threonine Kinase
chemistry.chemical_compound
Cell Movement
Luciferases
Aged, 80 and over
Antibiotics, Antineoplastic
TOR Serine-Threonine Kinase
Reverse Transcriptase Polymerase Chain Reaction
TOR Serine-Threonine Kinases
Liver Neoplasms
Cell Cycle
Intracellular Signaling Peptides and Proteins
MicroRNA
Middle Aged
Proto-Oncogene Proteins c-met
Gene Expression Regulation, Neoplastic
medicine.anatomical_structure
Oncology
Liver Neoplasm
Female
Luciferase
Human
medicine.drug
Carcinoma, Hepatocellular
C-Met
Liver Cirrhosi
Blotting, Western
Protein Serine-Threonine Kinases
Biology
microRNA
Cell Adhesion
medicine
Humans
Gene silencing
Doxorubicin
RNA, Messenger
PI3K/AKT/mTOR pathway
Aged
Cell Proliferation
RPTOR
Apoptosi
Cancer
medicine.disease
digestive system diseases
MicroRNAs
chemistry
Intracellular Signaling Peptides and Protein
Drug Resistance, Neoplasm
Cancer research
Subjects
Details
- ISSN :
- 15387445 and 00085472
- Volume :
- 70
- Database :
- OpenAIRE
- Journal :
- Cancer Research
- Accession number :
- edsair.doi.dedup.....b3bdb39d394a6e686dc59ad26bee4489