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Overexpression of microRNA-133b is associated with the increased survival of patients with hepatocellular carcinoma after curative hepatectomy: Involvement of the EGFR/PI3K/Akt/mTOR signaling pathway.
- Source :
-
Oncology reports [Oncol Rep] 2017 Jul; Vol. 38 (1), pp. 141-150. Date of Electronic Publication: 2017 Jun 06. - Publication Year :
- 2017
-
Abstract
- The aim of the present study was carried out to investigate the association of microRNA-133b (miRNA-133b) expression with the prognosis of patients with hepatocellular carcinoma (HCC) after curative hepatectomy. In the present study, the expression of miRNA-133b in HCC tissues was determined to be lower than that noted in the adjacent normal tissues. Overall and disease-free survival of the HCC patients with high miRNA-133b expression was observably extended, compared with the HCC patients with low miRNA‑133b expression. Moreover, the overexpression of miRNA-133b inhibited cell proliferation, increased lactate dehydrogenase (LDH) activity, induced apoptosis and promoted caspase‑3/-8 activities and Bax/Bcl-2 protein expression in HCC cells, whereas the protein expression of epidermal growth factor receptor (EGFR) was significantly decreased. The overexpression of miRNA-133b significantly suppressed PI3K, phosphorylated (p)-Akt and p-mTOR protein expression in HCC cells. GW2974, an EGFR inhibitor, suppressed the protein expression of EGFR, inhibited cell proliferation, increased LDH activity, induced apoptosis and promoted caspase-3/-8 activities and Bax/Bcl-2 protein expression, downregulated PI3K, p-Akt and p-mTOR protein expression in the transfected HCC cells overexpressing miRNA-133b. Taken together, our results indicate that the overexpression of miRNA-133b is associated with the increased survival of HCC patients after curative hepatectomy. The effects of miRNA-133b in HCC are mediated through the EGFR/PI3K/Akt/mTOR signaling pathway.
- Subjects :
- Apoptosis
Biomarkers, Tumor genetics
Biomarkers, Tumor metabolism
Carcinoma, Hepatocellular genetics
Carcinoma, Hepatocellular pathology
Carcinoma, Hepatocellular surgery
Cell Proliferation
ErbB Receptors genetics
Female
Gene Expression Regulation, Neoplastic
Hepatectomy mortality
Humans
Liver Neoplasms genetics
Liver Neoplasms pathology
Liver Neoplasms surgery
Male
Middle Aged
Phosphatidylinositol 3-Kinases genetics
Phosphorylation
Prognosis
Prospective Studies
Proto-Oncogene Proteins c-akt genetics
Signal Transduction
Survival Rate
TOR Serine-Threonine Kinases genetics
Tumor Cells, Cultured
Carcinoma, Hepatocellular mortality
ErbB Receptors metabolism
Liver Neoplasms mortality
MicroRNAs genetics
Phosphatidylinositol 3-Kinases metabolism
Proto-Oncogene Proteins c-akt metabolism
TOR Serine-Threonine Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1791-2431
- Volume :
- 38
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Oncology reports
- Publication Type :
- Academic Journal
- Accession number :
- 28586051
- Full Text :
- https://doi.org/10.3892/or.2017.5699