Insights into Regulation of the miR-17-92 Cluster of miRNAs in Cancer

Fuziwara, César Seigi; Kimura, Edna Teruko

doi:10.3389/fmed.2015.00064

Cited by 119 publications

(125 citation statements)

References 36 publications

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“…miR-17 is a tumor-related miRNA that serves important roles in the proliferation, invasion and metastasis of tumor cells (28). In AM, the invasion and metastastic abilities of endometrial cells are enhanced, which is an important cause of the disease (29).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-17 downregulates expression of the PTEN gene to promote the occurrence and development of adenomyosis

2017

Experimental and Therapeutic Medicine

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Abstract. The aim of the current study was to evaluate the expression of microRNA (miR)-17 in the endometrial tissues of patients with adenomyosis (AM) and determine its biological function in the occurrence and development of the disease. A total of 45 fresh endometrial tissues of AM patients and 32 normal endometrial tissues were collected from healthy controls. The expression of miR-17 was evaluated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The miR-17-targeting gene phosphatase and tensin homolog (PTEN) was predicted using bioinformatics and its expression was evaluated with RT-qPCR and western blot analysis. Endometrial cells were isolated from patients with AM and healthy controls. They were cultured in vitro and transfected with antagomiR-17 to downregulate miR-17 expression, subsequently cell viability and apoptosis were measured using MTT and flow cytometry. The expression of PTEN and cell cycle-and apoptosis-related proteins were evaluated using western blot analysis. Endometrial cells that stably overexpressed PTEN were screened in vitro by co-culture with G418. A dual-luciferase reporter assay was conducted to verify whether miR-17 was directly bound to PTEN mRNA. The results demonstrated that expression of miR-17 was significantly increased in the endometrial tissues of patients with AM compared with control patients (P<0.05). PTEN mRNA and protein expression were significantly lower in the AM group compared with the control group (P<0.05). When the expression of miR-17 in the cells was downregulated, the expression of PTEN was significantly increased (P<0.05). In addition, expression of Bcl-2 protein was significantly decreased and that of Bax protein significantly increased compared with the negative control (both P<0.05). The expression of cyclins E1 and D1 were also significantly downregulated (P<0.05). When PTEN was overexpressed or miR-17 was downregulated, the viability of endometrial cells significantly decreased and cell apoptosis significantly increased (all P<0.05). A dual-luciferase reporter assay indicated that miR-17 could directly bind to the PTEN mRNA 3'-untranslated region to regulate its expression. Thus the current study indicates that expression of miR-17 was increased in the endometrial tissues of patients with AM and may influence cell apoptosis and cyclin expression through the targeted regulation of PTEN. These results suggest that miR-17 promotes the occurrence and development of AM.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-17 downregulates expression of the PTEN gene to promote the occurrence and development of adenomyosis

2017

Experimental and Therapeutic Medicine

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“…The tumor-suppressive and tumorigenic properties of the miR-17-92 cluster are summarized in more detail in other recent reviews, e.g. [52,53]. …”

Section: Mir-17-5p and Its Role In Cancermentioning

confidence: 99%

MicroRNA-17-5p: At the Crossroads of Cancer and Aging - A Mini-Review

Dellago

Bobbili²,

Grillari³

2016

Gerontology

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The miR-17-92 cluster, led by its most prominent member, miR-17-5p, has been identified as the first miRNA with oncogenic potential. Thus, the whole cluster containing miR-17-5p has been termed oncomiR-1. It is strongly expressed in embryonic stem cells and has essential roles in vital processes like cell cycle regulation, proliferation and apoptosis. The importance of miR-17-5p for fundamental biological processes is underscored by the fact that a miR17-deficient mouse is neonatally lethal. Recently, miR-17-5p was identified in the context of aging, since it is comprised in a common signature of miRNAs that is downregulated in several models of aging research. Recently, miR-17-5p turned out to be the first ‘longevimiR' in an animal model, extending the lifespan of a transgenic miR-17-5p-overexpressing mouse. Here, we summarize the current status of research on miR-17-5p with emphasis on its role in cellular senescence, aging and cancer, which points to a pleiotropic function of miR-17-5p regulating multiple targets involved in autophagy, cell cycle regulation and apoptosis in a tissue-dependent fashion. In addition, its elevated presence in serum or plasma of a wide range of tumor patients suggests using it as an ‘alarmiR', a general indicator of a potential tumor pathology. However, amounts of circulating miR-17-5p of healthy individuals as reference values are still missing, before any miRNA can be classified as such an ‘alarmiR'. In conclusion, miR-17-5p is at the crossroads of aging, longevity and cancer and might represent a promising biomarker or even therapeutic tool and target in this context.

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“…However, therapeutic approaches that especially target the miR-17-92 cluster ( Figure 3B) should be considered carefully. The miR-17-92 cluster harbors several oncomirs that are associated with tumor progression and it is considered as a bona fide oncogene in lymphomagenesis (118,119). Therefore, such a strategy must be considered judiciously prior to potential application.…”

Section: Regulation Of Angiogenesismentioning

confidence: 99%

MicroRNAs: pleiotropic players in congenital heart disease and regeneration

et al. 2017

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Congenital heart disease (CHD) is the leading cause of infant death, affecting approximately 4-14 live births per 1,000. Although surgical techniques and interventions have improved significantly, a large number of infants still face poor clinical outcomes. MicroRNAs (miRs) are known to coordinately regulate cardiac development and stimulate pathological processes in the heart, including fibrosis or hypertrophy and impair angiogenesis. Dysregulation of these regulators could therefore contribute (I) to the initial development of CHD and (II) at least partially to the observed clinical outcomes of many CHD patients by stimulating the aforementioned pathways. Thus, miRs may exhibit great potential as therapeutic targets in regenerative medicine. In this review we provide an overview of miR function and elucidate their role in selected CHDs, including hypoplastic left heart syndrome (HLHS), tetralogy of Fallot (TOF), ventricular septal defects (VSDs) and Holt-Oram syndrome (HOS). We then bridge this knowledge to the potential usefulness of miRs and/or their targets in therapeutic strategies for regenerative purposes in CHDs.

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Insights into Regulation of the miR-17-92 Cluster of miRNAs in Cancer

Cited by 119 publications

References 36 publications

MicroRNA-17 downregulates expression of the PTEN gene to promote the occurrence and development of adenomyosis

MicroRNA-17 downregulates expression of the PTEN gene to promote the occurrence and development of adenomyosis

MicroRNA-17-5p: At the Crossroads of Cancer and Aging - A Mini-Review

MicroRNAs: pleiotropic players in congenital heart disease and regeneration

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