MicroRNA-130b promotes proliferation and EMT-induced metastasis via PTEN/p-AKT/HIF-1α signaling
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Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths owing to its high rate of postoperative recurrence and metastasis. New research is continuously identifying novel metastasis-associated oncogenes and tumor suppressor genes. miRNAs are noncoding RNAs that regulate protein synthesis post-translationally. miR-130b is one of several miRNAs involved in tumor metastasis. However, the role of miR-130b in HCC remains controversial. Here, we demonstrate that miR-130b is highly expressed in HCC and that it correlates with tumor number, vascular invasion, and TNM stage—important predictors of postoperative recurrence and metastases. Moreover, high levels of miR-130b predicted poor overall and disease-free survival of HCC patients, and in vitro and in vivo research revealed that knockdown or overexpression of miR-130b inhibited and promoted proliferation and metastasis of HCC cells, respectively. We identified PTEN as a direct functional target of miR-130b using miRNA databases and a dual luciferase report assay. Next, using a gain and loss assay and epithelial-mesenchymal transition (EMT) relative assays, we show that miR-130b may promote proliferation and EMT-induced metastasis via PTEN/p-AKT/HIF-1α signaling. Collectively, our data suggests that miR-130b may have prognostic value in HCC. Additionally, the miR-130b/PTEN/p-AKT/HIF-1α axis identified in this study provides novel insight into the mechanisms of HCC metastasis, which may facilitate the development of new therapeutics against HCC.
KeywordsSolitary large hepatocellular carcinoma miR-130b Prognosis EMT PTEN
Solitary large hepatocellular carcinoma
Small hepatocellular carcinoma
Nodular hepatocellular carcinoma
Adjacent nontumorous liver tissues
3′ Untranslated region
Quantitative reverse-transcription polymerase chain reaction
Phosphatase and tensin homolog
Compliance with ethical standards
This study was funded by Clinical Subjects’ Key Project of Ministry of Health (No. 2010439), National Science & Technology Major Projects (2009ZX09103-681, 2012ZX100020122011), National Nature Science Foundation of China (No. 81272395), Key Project of National Nature Science Foundation of China (No. 81330057), and The Specialized Research Fund for the Doctoral Program of Higher Education of China (No. 20130162130007).
Conflicts of interest
Prior informed consent was obtained from all patients and the study was approved by the Ethics Committee of Xiangya Hospital of CSU.
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