OIP5 is a highly expressed potential therapeutic target for colorectal and gastric cancers

Chun, Ho-Kyung; Chung, Kyung‐Sook; Kim, Hee Cheol; Kang, Ji-Sun; Kang, Min Sung; Kim, Jong-Tae; Choi, Eun Hwa; Jung, Kyuwhan; Kim, Moon-Hee; Song, Eun Young; Kim, Seon‐Young; Won, Misun; Lee, Hee Gu

doi:10.5483/bmbrep.2010.43.5.349

Cited by 43 publications

(26 citation statements)

References 21 publications

(11 reference statements)

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“…These results suggest that OIP5 expression is correlated with the mitotic proliferation of tumor cells, and that OIP5 knockdown-mediated inhibition of tumor cell growth causes accumulation of G 2 /M phase cell cycle regulators via OIP5/AKT signaling. Interestingly, our data also demonstrated that OIP5 knockdown induced apoptotic cell death, as reported previously [23]. …”

Section: Discussionsupporting

confidence: 91%

“…In addition, transient expression of OIP5 in NIH3T3 cells results in an increase in proliferation rate, highlighting its oncogenic properties [5]. Recently, OIP5 has also been reported to be upregulated in the tumors of colorectal cancer patients [6] and in female acute myeloid leukemia patients [7], implicating the protein as a potential therapeutic target for cancer [8]. Furthermore, it is a promising target for the development of new prognostic biomarkers and anti-cancer drugs in lung and esophageal cancers [9].…”

Section: Introductionmentioning

confidence: 99%

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OIP5, a target of miR-15b-5p, regulates hepatocellular carcinoma growth and metastasis through the AKT/mTORC1 and β-catenin signaling pathways

Zhang

Lee

et al. 2017

Oncotarget

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Opa interacting protein 5 (OIP5) is upregulated in some types of human cancers, but the biological implications of its upregulation have not yet been clarified in human hepatocellular carcinoma (HCC). In this study, the signaling pathway downstream of OIP5 was analyzed by proteome kinase profiling. A putative microRNA targeting OIP5 was identified using a miRNA PCR array. Tumorigenicity and metastatic ability were examined in an orthotopic animal model. OIP5 expression was strongly detected in early and advanced tumors via gene expression profiling and immunohistochemical staining analyses. Cells with knockdown of OIP5 via target shRNA exhibited reduced hepatic mass formation and metastatic tumor nodules in an orthotopic mouse model. OIP5-induced AKT activation was mediated by both mTORC2 and p38/PTEN activation. AKT activation was linked to mTORC1 and GSK-3β/β-catenin signaling, which are primarily associated with tumor cell growth and metastasis, respectively. miR-15b-5p, which targets OIP5, efficiently inhibited OIP5-mediated mTORC1 and GSK-3β/β-catenin signaling. These findings suggest that OIP5 may be involved in HCC growth and metastasis and that miR-15b-5p inhibits OIP5-mediated oncogenic signaling in HCC.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

OIP5, a target of miR-15b-5p, regulates hepatocellular carcinoma growth and metastasis through the AKT/mTORC1 and β-catenin signaling pathways

Zhang

Lee

et al. 2017

Oncotarget

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“…31, 32 Knockdown of OIP5 expression has been reported to inhibit cell growth of several cancer cell lines. 33, 34 The serine/threonine kinase Aurora-A plays a pivotal role in several mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis. 35 CKS2 associates with cyclin-dependent kinases and has been shown to play a direct role in cell cycle regulation.…”

Section: Discussionmentioning

confidence: 99%

Telmisartan Exerts Pleiotropic Effects in Endothelial Cells and Promotes Endothelial Cell Quiescence and Survival

Siragusa

Sessa

2013

ATVB

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Objective Telmisartan, an angiotensin II type 1 (AT1) receptor blocker, and amlodipine, a calcium channel blocker, are antihypertensive agents clinically used as monotherapy or in combination. They exert beneficial cardiovascular effects independently of blood pressure lowering and classic mechanisms of action. In this study, we investigate molecular mechanisms responsible for the off-target effects of telmisartan and telmisartan-amlodipine in endothelial cells (EC), using an unbiased genomic approach. Approach and Results In human umbilical vein endothelial cells, microarray analysis of gene expression followed by pathway enrichment analysis and quantitative PCR validation revealed that telmisartan modulates the expression of key genes responsible for cell cycle progression and apoptosis. Amlodipine’s effect was similar to control. EC exposed to telmisartan, but not amlodipine, losartan or valsartan, exhibited a dose-dependent impairment of cell growth and failed to enter the S-phase of the cell cycle. Similarly, telmisartan inhibited proliferation in COS-7 cells lacking the AT1 receptor. In telmisartan-treated EC, phosphorylation and activation of Akt as well as MDM2 was reduced, leading to accumulation of p53 in the nucleus, where it represses the transcription of cell cycle promoting genes. Phosphorylation of GSK3β was also reduced, resulting in rapid proteolytic turnover of CyclinD1. Telmisartan induced downregulation of proapoptotic genes and protected EC from serum starvation- and 7-ketocholesterol-induced apoptosis. Conclusions Telmisartan exerts antiproliferative and antiapoptotic effects in EC. This may account for the improved endothelial dysfunction observed in the clinical setting.

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“…Except for the findings as previously reported, we also predicted several novel potential chromosome aberrations, which were not found in previous array-based studies. Among them, a representative chromosome regions were located on the chromosome 15.1, which were enriched by a number of up-regulated carcinogenesis-related genes, such as OIP5 , a potential cancer therapeutic target [50], and PAK6 , a member of the p21-activated kinase (PAK) family of serine/threonine kinases, may play roles in the regulation of cell motility and in stress responses [51]. Our findings gave a deep insight into the HCC pathogenesis at the level of chromosome.…”

Section: Discussionmentioning

confidence: 99%

RNA-Seq Analyses Generate Comprehensive Transcriptomic Landscape and Reveal Complex Transcript Patterns in Hepatocellular Carcinoma

et al. 2011

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RNA-seq is a powerful tool for comprehensive characterization of whole transcriptome at both gene and exon levels and with a unique ability of identifying novel splicing variants. To date, RNA-seq analysis of HBV-related hepatocellular carcinoma (HCC) has not been reported. In this study, we performed transcriptome analyses for 10 matched pairs of cancer and non-cancerous tissues from HCC patients on Solexa/Illumina GAII platform. On average, about 21.6 million sequencing reads and 10.6 million aligned reads were obtained for samples sequenced on each lane, which was able to identify >50% of all the annotated genes for each sample. Furthermore, we identified 1,378 significantly differently expressed genes (DEGs) and 24, 338 differentially expressed exons (DEEs). Comprehensive function analyses indicated that cell growth-related, metabolism-related and immune-related pathways were most significantly enriched by DEGs, pointing to a complex mechanism for HCC carcinogenesis. Positional gene enrichment analysis showed that DEGs were most significantly enriched at chromosome 8q21.3–24.3. The most interesting findings were from the analysis at exon levels where we characterized three major patterns of expression changes between gene and exon levels, implying a much complex landscape of transcript-specific differential expressions in HCC. Finally, we identified a novel highly up-regulated exon-exon junction in ATAD2 gene in HCC tissues. Overall, to our best knowledge, our study represents the most comprehensive characterization of HBV-related HCC transcriptome including exon level expression changes and novel splicing variants, which illustrated the power of RNA-seq and provided important clues for understanding the molecular mechanisms of HCC pathogenesis at system-wide levels.

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OIP5 is a highly expressed potential therapeutic target for colorectal and gastric cancers

Cited by 43 publications

References 21 publications

OIP5, a target of miR-15b-5p, regulates hepatocellular carcinoma growth and metastasis through the AKT/mTORC1 and β-catenin signaling pathways

OIP5, a target of miR-15b-5p, regulates hepatocellular carcinoma growth and metastasis through the AKT/mTORC1 and β-catenin signaling pathways

Telmisartan Exerts Pleiotropic Effects in Endothelial Cells and Promotes Endothelial Cell Quiescence and Survival

RNA-Seq Analyses Generate Comprehensive Transcriptomic Landscape and Reveal Complex Transcript Patterns in Hepatocellular Carcinoma

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