Somatic mutation and loss of expression of a candidate tumor suppressor gene TET3 in gastric and colorectal cancers

Publication date: Available online 14 December 2019Source: Pathology - Research and PracticeAuthor(s): Ha Yoon Mo, Chang Hyeok An, Eun Ji Choi, Nam Jin Yoo, Sug Hyung LeeABSTRACTTen-eleven translocation 3 (TET3) is responsible for the DNA methylation and plays an important role in regulation of the gene expression. TET2, another TET, is frequently mutated in hematologic malignancies and considered a driver gene for leukemogenesis. TET3 mRNA downregulation has been identified in many solid cancers, suggesting its role as a candidate tumor suppressor gene (TSG). However, somatic inactivating mutation and protein expression in solid cancers are largely unknown. The aim of our study was to find whether TET3 gene was mutated and expressionally altered in gastric (GC) and colorectal cancers (CRC). TET3 gene possesses mononucleotide repeats in the coding sequence that could be mutated in cancers with high microsatellite instability (MSI-H). We analyzed 79 GCs and 124 CRCs, and found that GCs (2.9%) and CRCs (7.6%) with MSI-H, but not those with microsatellite stable/low MSI (MSS), harbored frameshift mutations within the repeats. In immunohistochemistry, loss of TET3 expression was identified in 32% of GCs and 28% of CRCs. Positive TET3 immunostaining in MSI-H cancers with TET3 frameshift mutation (1/7) was significantly lower than that without TET3 frameshift mutations (75/110). Our data may indicate TET3 harbored not only frameshift mutation but also loss of expression, which toge...
Source: Pathology Research and Practice - Category: Pathology Source Type: research

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Abstract Ten-eleven translocation 3 (TET3) is responsible for the DNA methylation and plays an important role in regulation of the gene expression. TET2, another TET, is frequently mutated in hematologic malignancies and considered a driver gene for leukemogenesis. TET3 mRNA downregulation has been identified in many solid cancers, suggesting its role as a candidate tumor suppressor gene (TSG). However, somatic inactivating mutation and protein expression in solid cancers are largely unknown. The aim of our study was to find whether TET3 gene was mutated and expressionally altered in gastric (GC) and colorectal ca...
Source: Pathology, Research and Practice - Category: Pathology Authors: Tags: Pathol Res Pract Source Type: research
In conclusion, TTB inhibited OGD/R-induced astrocytes oxidative stress, at least partially through inhibition of HIF1α and VEGF via Nrf2/HO-1 signaling pathway.
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusions: Primary carcinoma with plasmacytoid morphology is a dedifferentiated variant of adenocarcinoma or poorly cohesive carcinomas. Vimentin positive dedifferentiated-poorly cohesive carcinomas should be considered as mesenchymal-type highly malignant carcinomas. This rare histologic variant of gastrointestinal cancer might respond to anti-c-MET tyrosine kinases. PMID: 31205468 [PubMed]
Source: Journal of Oncology - Category: Cancer & Oncology Tags: J Oncol Source Type: research
Alessandro Poggi1*, Roberto Benelli2, Roberta Venè1, Delfina Costa1, Nicoletta Ferrari1, Francesca Tosetti1 and Maria Raffaella Zocchi3 1Molecular Oncology and Angiogenesis Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy 2Immunology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy 3Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy It is well established that natural killer (NK) cells are involved in both innate and adaptive immunity. Indeed, they can recognize molecules induced at the cell surface by stress signals ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion MTDH is pro-oncogenic factor playing multifaceted and diverse roles in cancer progression. Its association and central role in regulating signaling pathways such a MAPK, wnt/β-catenin, PI3K/AkT, NF-κβ pathways in various cancers shows that it plays a vital role in metastasis. MTDH contribution to chemo and radiotherapy resistance provides a new direction for the development of anticancer therapeutics. Multiple mechanisms converge to promote expression of MTDH in cancers. Further studies are therefore warranted to determine whether the elevated MTDH expression has prognostic value for development...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions This review describes how leukocyte-heparanase can be a double-edged sword in tumor progression; it can enhance tumor immune surveillance and tumor cell clearance, but also promote tumor survival and growth. We also discuss the potential of using heparanase in leukocyte therapies against tumors, and the effects of heparanase inhibitors on tumor progression and immunity. We are just beginning to understand the influence of heparanase on a pro/anti-tumor immune response, and there are still many questions to answer. How do the pro/anti-tumorigenic effects of heparanase differ across different cancer types? Does...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In this study we adopted an all-in-one method. Primers designed according to the two gRNA sequences and the tracRNA-U6 vector sequences were used to produce a gRNA1-tracRNA-U6-gRNA2 fragment. Then the proper fragment was ligated into the lentiCRISPRv2 vector and verified by sequencing. Lentiviral Packaging and Stable Cell Line Screening The constructed eukaryotic expression vector and gene knockdown vector were transfected into the 293T cells with the packaging plasmids psPAX2 and pMD2.G using Lipofectamine 2000 (Thermo Fisher, Massachusetts, USA). The lentivirus was harvested 48 h after transfection, and the lentivirus ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
This study was carried out in accordance with the recommendations of international guidelines and ethical standards with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the Institutional Ethics Committee of Kunming General Hospital, China. miRNAs, Plasmids, Transfection, and Irradiation To predict miRNAs with potential binding sites in the 3′UTR of PHLDA2, Targetscan (http://www.targetscan.org/), miRanda (http://www.microrna.org/), and Diana database (http://diana.cslab,ece.nura.gr/) algorithms were u...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Minghui Wan†, Lei Zhang†, Yiming Chen, Qiang Li, Wenli Fan, Qingxia Xue, Fang Yan* and Weiguo Song* School of Pharmacy, Weifang Medical University, Weifang, China Based on the structure of sanguinarine, fourteen phenanthridine derivatives were designed and synthesized in the current study. The cytotoxic activities of synthesized compounds were evaluated against five human cancer cell lines (MCF-7, PC3, Hela, A549, and HepG2 cell lines) via MTT assay. Among all the compounds tested, molecule 8a exhibited significant cytotoxic activity against MCF-7 cells with a IC50 value of 0.28 μM. A following u...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusion Most head and neck pathologies show a broad cellular heterogeneity making it difficult to achieve an accurate diagnosis and efficient treatment (Graf and Zavodszky, 2017; Lo Nigro et al., 2017). Single cell analysis of circadian omics (Lande-Diner et al., 2015; Abraham et al., 2018), may be a crucial tool needed in the future to fully understand the circadian control of head and neck diseases. It becomes more obvious that there is only a small genetic component but a largely unknown epigenetics and/or environmental component for most of the head and neck pathologies (Moosavi and Motevalizadeh Ardekani, 2016; He...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
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