MiR-138 Induces Renal Carcinoma Cell Senescence by Targeting EZH2 and Is Downregulated in Human Clear Cell Renal Cell Carcinoma

Liang, Jintai; Zhang, Yajing; Jiang, Guosong; Liu, Zhouqiang; Xiang, Wei; Chen, Xuanyu; Chen, Zhaohui; Zhao, Jun

doi:10.3727/096504013x13775486749218

Cited by 62 publications

(42 citation statements)

References 22 publications

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“…To the best of our knowledge, the present study is the first to demonstrate that miR-138 expression is significantly downregulated in cervical cancer tissues and cell lines, and that low miR-138 expression is negatively associated with advanced FIGO stage and lymph node metastasis. In addition, miR-138 has been previously reported to function as a tumor suppressor in numerous malignancies by targeting various molecules (13)(14)(15)(16)(17)(18)(19). For cervical cancer, a study showed that miR-138 could significantly inhibit HeLa cell migration by targeting required for meiotic nuclear division 5 homolog A (29).…”

Section: Discussionmentioning

confidence: 99%

“…miR-138, a family of microRNA precursors, has been reported to function as a tumor suppressor in a variety of human cancers, including renal carcinoma (13), non-small lung cancer (14), colorectal cancer (15), neuroblastoma (16), esophageal squamous cell carcinoma (17), nasopharyngeal carcinoma (18) and hepatocellular carcinoma (19). However, the role and the molecular mechanisms of miR-138 in cervical remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA-138 inhibits proliferation, migration and invasion through targeting hTERT in cervical cancer

et al. 2016

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Abstract.A growing body of evidence suggests that microRNA-138 (miR-138) functions as a tumor suppressor, and is involved in tumor initiation, development and metastasis in certain types of human cancers. However, the function and underlying molecular mechanism of miR-138 in cervical cancer remains unclear. Therefore, the purpose of the present study was to investigate the clinical significance of miR-138 expression in cervical cancer, and to evaluate its role and underlying mechanisms in cervical cancer. The present study indicated that miR-138 expression was significantly downregulated in cervical cancer tissues and cell lines, and that the low miR-138 expression was negatively associated with advanced FIGO stage and lymph node metastasis (P<0.01). Functional analyses indicated that the overexpression of miR-138 in cervical cancer cells inhibited cell proliferation, migration and invasion, induced cell apoptosis in vitro, and suppressed tumor growth in a nude mice model. Luciferase reporter assays confirmed that human telomerase reverse transcriptase was a novel target gene of miR-138. The findings of the present study suggested that miR-138 could be a potential candidate for cervical cancer therapeutics.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

MicroRNA-138 inhibits proliferation, migration and invasion through targeting hTERT in cervical cancer

et al. 2016

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“…36 EZH2 is under the regulatory control of several miRs, including but not limited to miR-26a, miR-98, miR-101, miR-124, and miR-138. 9,37,38 The best characterized of these is miR-101. 39 Consistent with the effect of miR-101 in inhibiting EZH2 translation, we observed a profound increase in EZH2 protein in podocytes exposed to an oligonucleotide inhibitor of this miR.…”

Section: Discussionmentioning

confidence: 99%

The Histone Methyltransferase Enzyme Enhancer of Zeste Homolog 2 Protects against Podocyte Oxidative Stress and Renal Injury in Diabetes

Siddiqi

Majumder

Thai

et al. 2015

JASN

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Epigenetic regulation of oxidative stress is emerging as a critical mediator of diabetic nephropathy. In diabetes, oxidative damage occurs when there is an imbalance between reactive oxygen species generation and enzymatic antioxidant repair. Here, we investigated the function of the histone methyltransferase enzyme enhancer of zeste homolog 2 (EZH2) in attenuating oxidative injury in podocytes, focusing on its regulation of the endogenous antioxidant inhibitor thioredoxin interacting protein (TxnIP). Pharmacologic or genetic depletion of EZH2 augmented TxnIP expression and oxidative stress in podocytes cultured under high-glucose conditions. Conversely, EZH2 upregulation through inhibition of its regulatory microRNA, microRNA-101, downregulated TxnIP and attenuated oxidative stress. In diabetic rats, depletion of EZH2 decreased histone 3 lysine 27 trimethylation (H3K27me3), increased glomerular TxnIP expression, induced podocyte injury, and augmented oxidative stress and proteinuria. Chromatin immunoprecipitation sequencing revealed H3K27me3 enrichment at the promoter of the transcription factor Pax6, which was upregulated on EZH2 depletion and bound to the TxnIP promoter, controlling expression of its gene product. In high glucose-exposed podocytes and the kidneys of diabetic rats, the lower EZH2 expression detected coincided with upregulation of Pax6 and TxnIP. Finally, in a gene expression array, TxnIP was among seven of 30,854 genes upregulated by high glucose, EZH2 depletion, and the combination thereof. Thus, EZH2 represses the transcription factor Pax6, which controls expression of the antioxidant inhibitor TxnIP, and in diabetes, downregulation of EZH2 promotes oxidative stress. These findings expand the extent to which epigenetic processes affect the diabetic kidney to include antioxidant repair.

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“…Epigenetic-driven gene expression profiles are dynamic, and, therefore, the complexity added due to obesity (59) and diabetes (126) needs to be evaluated systematically. (1,25,28,32,37,55,57,66,74,81,88,90,93,107,108,110,117,124,137,155,156,162). Studies examining the upstream and downstream regulation of miRNAs on oxidative stress in human disease are recently becoming available.…”

Section: Epigenetic Modification In Renal Carcinomamentioning

confidence: 99%

Renal Carcinogenesis, Tumor Heterogeneity, and Reactive Oxygen Species: Tactics Evolved

Shanmugasundaram

Block

2016

Antioxidants & Redox Signaling

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Significance: The number of kidney cancers is growing 3-5% each year due to unknown etiologies. Intra-and inter-tumor mediators increase oxidative stress and drive tumor heterogeneity. Recent Advances: Technology advancement in state-of-the-art instrumentation and methodologies allows researchers to detect and characterize global landscaping modifications in genes, proteins, and pathophysiology patterns at the single-cell level. Critical Issues: We postulate that the sources of reactive oxygen species (ROS) and their activation within subcellular compartments will change over a timeline of tumor evolvement and contribute to tumor heterogeneity. Therefore, the complexity of intracellular changes within a tumor and ROS-induced tumor heterogeneity coupled to the advancement of detecting these events globally are limited at the level of data collection, organization, and interpretation using software algorithms and bioinformatics. Future Directions: Integrative and collaborative research, combining the power of numbers with careful experimental design, protocol development, and data interpretation, will translate cancer biology and therapeutics to a heightened level or leave the abundant raw data as stagnant and underutilized. Antioxid. Redox Signal. 25, 685-701.

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MiR-138 Induces Renal Carcinoma Cell Senescence by Targeting EZH2 and Is Downregulated in Human Clear Cell Renal Cell Carcinoma

Cited by 62 publications

References 22 publications

MicroRNA-138 inhibits proliferation, migration and invasion through targeting hTERT in cervical cancer

MicroRNA-138 inhibits proliferation, migration and invasion through targeting hTERT in cervical cancer

The Histone Methyltransferase Enzyme Enhancer of Zeste Homolog 2 Protects against Podocyte Oxidative Stress and Renal Injury in Diabetes

Renal Carcinogenesis, Tumor Heterogeneity, and Reactive Oxygen Species: Tactics Evolved

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