RASSF tumor suppressor gene family: Biological functions and regulation

Volodko, Natalia; Gordon, Myron J.; Salla, Mohamed; Ghazaleh, Haya Abu; Baksh, Shairaz

doi:10.1016/j.febslet.2014.02.041

Cited by 116 publications

(123 citation statements)

References 185 publications

(387 reference statements)

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“…Therefore, miR-214 regulates cell apoptosis through suppressing RASSF5, which inhibits FOXO3a phosphorylation and BIM expression. The exact mechanism of RASSF5 down-regulation in oral cancer remains unclear, though some other studies have demonstrated that hyper-methylation of the RASSF5 promoter might be involved in the down-regulation of RASSF5 in several cancers (Hesson et al, 2003;Volodko et al, 2014). However, the hyper-methylation of RASSF5 promoter was not measured in our study and is the main study limitation.…”

Section: Discussionmentioning

confidence: 66%

MiR-214 regulates oral cancer KB cell apoptosis through targeting RASSF5

Yin

Chen

et al. 2017

Genet. Mol. Res.

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ABSTRACT. Ras association domain family member 5 (RASSF5), a member of the Ras association domain family, induces cell apoptosis by phosphorylating FOXO3a, which triggers target gene BIM (proapoptotic factor) activation. MiR-214 is overexpressed in oral cancer tissue, indicating its possible involvement in oral cancer pathogenesis. Bioinformatics analysis has revealed a complimentary sequence between miR-214 and the 3'-UTR of RASSF5 mRNA. However, whether miR-124 regulates RASSF5 in oral cancer remains poorly understood. We aimed to investigate the role of miR-214 in RASSF5 expression regulation in oral cancer. Tumor and paracarcinoma tissues were obtained from 48 oral cancer patients to examine miR-214 and RASSF5 expression. The relationship between miR-214 and RASSF5 was investigated by dual luciferase reporter gene assay. Oral cancer KB cells were cultured in vitro and divided into inhibitor NC, miR-214 inhibitor, Scramble-pMD18, RASSF5-pMD18, and miR-214 inhibitor + RASSF5-pMD18 groups. Caspase 3 activity, cell apoptosis, and total protein expression were measured by spectrophotometry, flow cytometry, and western blot, respectively. MiR-214 expression was significantly increased, while that of RASSF5 decreased in oral cancer tumor tissues compared to paracarcinoma tissues. Luciferase assay showed that miR-214 suppressed RASSF5 expression by targeting its 3'-UTR. Down-regulation of miR-214 and/or enhancement of RASSF5 expression markedly increased FOXO3a phosphorylation, BIM expression, caspase 3 activity, and apoptosis. In conclusion, miR-214 expression was elevated and RASSF5 was down-regulated in oral cancer. Moreover, miR-214 regulated KB cell apoptosis through targeted inhibition of RASSF5 expression, FOXO3a phosphorylation, and BIM expression, suggesting its possible application as a novel therapeutic oral cancer target.

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Section: Discussionmentioning

confidence: 66%

MiR-214 regulates oral cancer KB cell apoptosis through targeting RASSF5

Yin

Chen

et al. 2017

Genet. Mol. Res.

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“…One potential mechanism for hypermethylation-induced silencing is changing the structure of specific binding sites for certain transcriptional regulators (24). Epigenetic silencing of genes by promoter hypermethylation is associated with the loss of tumor suppression, increasing tumor severity and reducing patient survival (25). The present meta-analysis revealed significant changes in the methylation status of the CDKN2A, CDKN2B, ID4, GliPR1, p73 and Wilms' tumor 1 (WT1) genes in the major types of leukemia (21,23,(26)(27)(28).…”

Section: Discussionmentioning

confidence: 99%

DNA methylation and leukemia susceptibility in China: Evidence from an updated meta-analysis

Jiang

Hong

et al. 2016

Molecular and Clinical Oncology

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Abstract. Mounting evidence supports a role for DNA methylation in the pathogenesis of leukemia; however, there no overview of these results in the Chinese population. The present study performed a comprehensive meta-analysis to establish candidate genes with an altered methylation status in Chinese leukemia patients. Eligible studies were identified through searching the National Center of Biotechnology Information PubMed and Wanfang databases. Studies were pooled and overall odds ratios with corresponding confidence intervals were calculated. A total of 4,325 leukemia patients and 2,010 controls from 94 studies on 53 genes were included in this meta-analysis, and 47 genes were found to be aberrantly methylated in leukemia patients. A further subgroup meta-analysis by leukemia subtype demonstrated that hypermethylation of 5 genes, namely cyclin-dependent kinase (CDKN)2A, DNA-binding protein inhibitor-4, CDKN2B, glioma pathogenesis-related protein 1 and p73, contributed to the risk of various subtypes of leukemia. In addition, a strong association between CDKN2A and leukemia was identified in Chinese (P<0.00001) but not in European patients. The aberrantly methylated genes identified in the present meta-analysis may help elucidate the mechanisms underlying the development of leukemia in Chinese patients.

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“…SAV1 contains two WW domains and a SARAH domain in the C-terminal region [38]. RASSF family contains 10 members, namely RASSF1 to RASSF10 [39,40]. RASSF5 is also known as new Ras effector 1 (NORE1) and regulator for cell adhesion and polarization enriched in lymphoid tissues (RAPL).…”

Section: Core Kinase Cascadementioning

confidence: 99%

Structural dissection of Hippo signaling

Shi¹,

Shi

Zhou

2015

ABBS

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The Hippo pathway controls cell number and organ size by restricting cell proliferation and promoting apoptosis, and thus is a key regulator in development and homeostasis. Dysfunction of the Hippo pathway correlates with many pathological conditions, especially cancer. Hippo signaling also plays important roles in tissue regeneration and stem cell biology. Therefore, the Hippo pathway is recognized as a crucial target for cancer therapy and regeneration medicine. To date, structures of several key components in Hippo signaling have been determined. In this review, we summarize current available structural studies of the Hippo pathway, which may help to improve our understanding of its regulatory mechanisms, as well as to facilitate further functional studies and potential therapeutic interventions.

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RASSF tumor suppressor gene family: Biological functions and regulation

Cited by 116 publications

References 185 publications

MiR-214 regulates oral cancer KB cell apoptosis through targeting RASSF5

MiR-214 regulates oral cancer KB cell apoptosis through targeting RASSF5

DNA methylation and leukemia susceptibility in China: Evidence from an updated meta-analysis

Structural dissection of Hippo signaling

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