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MicroRNA 130 family regulates the hypoxia response signal through the P-body protein DDX6.

ABSTRACT: The transcription factor HIF-1? (hypoxia inducible factor 1?) has an essential role in the maintenance of oxygen homeostasis in metazoans. HIF-1? expression and activity in the hypoxic response is regulated at the translation and post-translational levels. However, the mechanism and modulator of HIF-1? translation during hypoxia is not fully understood. We found that HIF-1? expression during hypoxia was upregulated by the microRNA 130 (miR-130) family. Levels of the miR-130 family are elevated under hypoxia, and their target is DDX6 mRNA, which is a component of the P-bodies. Furthermore, we found that a decrease of DDX6 expression by the miR-130 family enhanced the translation of HIF-1? in an internal ribosome entry site element-dependent manner. These results reveal a new HIF-1? translational mechanism and a role for P-bodies in hypoxic stress.

SUBMITTER: Saito K

PROVIDER: S-EPMC3152344 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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MicroRNA 130 family regulates the hypoxia response signal through the P-body protein DDX6.

Saito Ken K Kondo Eisaku E Matsushita Masayuki M

Nucleic acids research 20110412 14

The transcription factor HIF-1α (hypoxia inducible factor 1α) has an essential role in the maintenance of oxygen homeostasis in metazoans. HIF-1α expression and activity in the hypoxic response is regulated at the translation and post-translational levels. However, the mechanism and modulator of HIF-1α translation during hypoxia is not fully understood. We found that HIF-1α expression during hypoxia was upregulated by the microRNA 130 (miR-130) family. Levels of the miR-130 family are elevated u ...[more]

PMID: 21486751

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Project description:BackgroundEmerging evidence shows that microRNA-130 (miRNA-130) family may be useful as prognostic biomarkers in cancer. However, there is no confirmation in an independent validation study. The aim of this study was to summarize the prognostic value of miRNA-130 family (miRNA-130a and miRNA-130b) for survival in patients with cancer.MethodsThe pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to estimate the association strength between miRNA-130 family expression and prognosis. Kaplan-Meier plotters were used to verify the miRNA-130b expression and overall survival (OS).ResultsA total of 2141 patients with OS and 1159 patients with disease-free survival (DFS)/progression-free survival (PFS) were analyzed in evidence synthesis. For the miRNA-130a, the overall pooled effect size (HR) was HR 1.58 (95% CI: 1.21-2.06, P?<?0.001). Tissue and serum expression of miRNA-130a was significantly associated with the OS (HR?=?1.54, 95% CI: 1.11-2.14, P?=?0.009; HR?=?1.65, 95% CI: 1.14-2.38, P?=?0.008), and in gastric cancer (HR?=?1.81, 95% CI: 1.34-2.45, P?<?0.001). For the miRNA-13b, a statistical correlation was observed between high miRNA-130b expression and poor OS in patients with cancer (HR?=?1.95, 95% CI: 1.47-2.59, P?<?0.001), especially in tissue sample (HR?=?2.01, 95% CI: 1.39-2.91, P?<?0.001), Asian (HR?=?2.55, 95% Cl: 1.77-3.69, P?<?0.001) and hepatocellular carcinoma (HR?=?1.87, 95% CI: 1.23-2.85, P?=?0.004). The expression of miRNA-130b was significantly correlated with DFS/PFS (HR?=?1.53, 95% CI: 1.31-1.77, P?<?0.001), in tissue (HR?=?1.98, 95% CI: 1.50-2.62, P?<?0.001) and serum (HR?=?1.37, 95% CI: 1.15-1.64, P?<?0.001), especially in HCC (HR?=?1.98, 95% CI: 1.50, 2.62, P?<?0.001). In database test, a significant correlation between high miRNA-130b expression and poor OS for HCC patients was observed (HR?=?1.55, 95% CI: 1.01, 2.35, P?=?0.0045).ConclusionThe high expression of miRNA-130 family might predict poor prognosis in cancer patients. Prospectively, combining miRNA-130a and miRNA-130b may be considered as powerful prognostic predictor for clinical application.

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MicroRNA 130 family regulates the hypoxia response signal through the P-body protein DDX6.

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MicroRNA 130 family regulates the hypoxia response signal through the P-body protein DDX6.

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