Gain-of-function microRNA screens identify miR-193a regulating proliferation and apoptosis in epithelial ovarian cancer cells

Nakano, Hitoo; Yamada, Yoji; Miyazawa, Tatsuya; Yoshida, Tatsushi

doi:10.3892/ijo.2013.1896

Cited by 98 publications

(68 citation statements)

References 40 publications

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“…In order to inspect if miR-192 downregulation was functionally involved in cancer pathophysiology or a mere indicator of pancreatic abnormality, functional experiments were carried out both in vitro and in vivo, indicating a tumor suppressor role of miR-192 in PDAC. This finding is in agreement with earlier reports that have suggested a tumor suppressor function of miR-192 in other cancers, such as lung (25), breast (26), and epithelial ovarian cancer (27). Additionally, our observation that patients with high miR-192 levels in the tumor have significantly longer survival times indicates that miR-192 expression contributes to the invasive power of PDAC, as most PDAC-associated deaths are due to metastasis.…”

Section: Discussionsupporting

confidence: 83%

Early Epigenetic Downregulation of microRNA-192 Expression Promotes Pancreatic Cancer Progression

et al. 2016

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Pancreatic ductal adenocarcinoma (PDAC) is characterized by very early metastasis, suggesting the hypothesis that metastasisassociated changes may occur prior to actual tumor formation. In this study, we identified miR-192 as an epigenetically regulated suppressor gene with predictive value in this disease. miR-192 was downregulated by promoter methylation in both PDAC and chronic pancreatitis, the latter of which is a major risk factor for the development of PDAC. Functional studies in vitro and in vivo in mouse models of PDAC showed that overexpression of miR-192 was sufficient to reduce cell proliferation and invasion. Mechanistic analyses correlated changes in miR-192 promoter methylation and expression with epithelial-mesenchymal transition. Cell proliferation and invasion were linked to altered expression of the miR-192 target gene SERPINE1 that is encoding the protein plasminogen activator inhibitor-1 (PAI-1), an established regulator of these properties in PDAC cells. Notably, our data suggested that invasive capacity was altered even before neoplastic transformation occurred, as triggered by miR-192 downregulation. Overall, our results highlighted a role for miR-192 in explaining the early metastatic behavior of PDAC and suggested its relevance as a target to develop for early diagnostics and therapy.

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Section: Discussionsupporting

confidence: 83%

Early Epigenetic Downregulation of microRNA-192 Expression Promotes Pancreatic Cancer Progression

et al. 2016

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“…Functional studies of these miRNAs would be helpful for a better understanding of their contribution to the pathophysiology of schizophrenia. The validated downstream target genes for miR-130b include PDGFRA, RUNX3, ITGB1, PPARG, FMR1, and STAT3, and for miR-193a-3p they include ErbB4, S6K2, and MCL1 (33)(34)(35)(36)(37)(38)(39). These genes can be classified into three groups: schizophrenia susceptibility genes (PDGFRA, PPARG, ErbB4), neurodevelopment-related genes (RUNX3, ITGB1, FMR1, STAT3), and neuroprotective genes (S6K2 and MCL1).…”

Section: Discussionmentioning

confidence: 99%

Detection of Circulating miRNA Levels in Schizophrenia

Wei

Yuan²,

Li³

et al. 2015

AJP

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Objective: Diagnosis of schizophrenia is currently dependent on symptom-based criteria and lacks objective indicators. In this study, the authors investigated whether circulating miRNA can serve as a diagnostic biomarker for schizophrenia.Methods: Global plasma miRNAs were profiled in a test cohort of 164 schizophrenia patients and 187 control subjects, using Solexa sequencing, TaqMan Low Density Array, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. The captured miRNAs were then validated by qRT-PCR assays in an independent cohort of 400 schizophrenia patients, 213 control subjects, and 162 patients with nonschizophrenia psychiatric disorders; the 400 schizophrenia patients underwent a 12-month follow up study of regular treatment with an atypical antipsychotic (risperidone and aripiprazole). Results:The global plasma miRNA screening revealed eight miRNAs that were up-regulated in schizophrenia, as revealed by both assay platforms. The qRT-PCR analysis showed the up-regulation of miR-130b and miR-193a-3p in schizophrenia but not in nonschizophrenia disorders. Conclusions:The up-regulation of miR-130b and miR-193a-3p is a state-independent biomarker for schizophrenia, and these two miRNAs could be used to develop a diagnostic tool for schizophrenia.

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“…Studies have shown that miRNAs are involved in the regulation of cancer cell proliferation and apoptosis (26)(27).…”

Section: Discussionmentioning

confidence: 99%

Upregulation of microRNA-23a regulates proliferation and apoptosis by targeting APAF-1 in laryngeal carcinoma

et al. 2015

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Abstract. ) is a potential biomarker for laryngeal cancer. Apoptotic protease activating factor 1 (APAF-1) was recently demonstrated to be a target of miR-23a. However, whether miR-23a exerts its effects via APAF-1 in laryngeal cancer, remains unknown. In the present study, miR-23a expression was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). APAF-1 mRNA and protein expression levels were assayed by RT-qPCR and western blotting, respectively. Binding of miR-23a to APAF-1 was monitored by a luciferase reporter assay. Gain-of-function and loss-of-function studies were performed in order to investigate the roles of miR-23a and APAF-1 in Hep2 cell proliferation and apoptosis. miR-23a and APAF-1 were found to be significantly upregulated and downregulated, respectively, in laryngeal cancer tissues, and there was a significant negative correlation between APAF-1 and miR-23a expression. The results of the luciferase reporter assay demonstrated that miR-23a bound directly to the APAF-1 mRNA 3'-untranslated region. Ectopic expression of miR-23a and knockdown of APAF-1 significantly promoted cell proliferation and colony formation, and inhibited early apoptosis in Hep2 cells. In conclusion, miR-23a acts as an oncogenic regulator in laryngeal carcinoma by directly targeting APAF-1, and may be a useful biomarker in the diagnosis and treatment of laryngeal carcinoma.

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Gain-of-function microRNA screens identify miR-193a regulating proliferation and apoptosis in epithelial ovarian cancer cells

Cited by 98 publications

References 40 publications

Early Epigenetic Downregulation of microRNA-192 Expression Promotes Pancreatic Cancer Progression

Early Epigenetic Downregulation of microRNA-192 Expression Promotes Pancreatic Cancer Progression

Detection of Circulating miRNA Levels in Schizophrenia

Upregulation of microRNA-23a regulates proliferation and apoptosis by targeting APAF-1 in laryngeal carcinoma

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