Molecular and Cellular Biology / Genetics最新文献

{"title":"Abstract 2409: The regulation of mitochondria metabolism is correlated with gemcitabine resistance in MIA-PaCa-2 cell line","authors":"Rina Fujiwara-Tani, Shingo Kishi, S. Mori, H. Kuniyasu","doi":"10.1158/1538-7445.AM2021-2409","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2409","url":null,"abstract":"","PeriodicalId":18754,"journal":{"name":"Molecular and Cellular Biology / Genetics","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84098002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract LB201: Understanding genetic variation in cancer using nanopore targeted sequencing","authors":"S. Iyer, M. Kramer, Sara Goodwin, W. McCombie","doi":"10.1158/1538-7445.AM2021-LB201","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-LB201","url":null,"abstract":"","PeriodicalId":18754,"journal":{"name":"Molecular and Cellular Biology / Genetics","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80537137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 1969: PTEN plays a role in histone modifications during mitosis","authors":"B. Choi, T. Colon, Eunji Lee, Ziyue Kou, Wei Dai","doi":"10.1158/1538-7445.AM2021-1969","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-1969","url":null,"abstract":"","PeriodicalId":18754,"journal":{"name":"Molecular and Cellular Biology / Genetics","volume":"85 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80564227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 2367: Role of miR-34a-MET axis in head and neck cancer squamous cell carcinoma","authors":"Xun Wu, Y. Cheng, Methew Matthen, A. Yoon, G. Schwartz, S. Bala, Alison M. Taylor, F. Momen-Heravi","doi":"10.1158/1538-7445.AM2021-2367","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2367","url":null,"abstract":"","PeriodicalId":18754,"journal":{"name":"Molecular and Cellular Biology / Genetics","volume":"79 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80661452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 2073: Co-Targeting PARP and ATR in biliary tract cancer","authors":"Ah-Rong Nam, M. Jin, K. Oh, Hye-Rim Seo, Jae-Min Kim, J. Bang, J. Yoon, T. M. Kim, D. Oh","doi":"10.1158/1538-7445.AM2021-2073","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2073","url":null,"abstract":"","PeriodicalId":18754,"journal":{"name":"Molecular and Cellular Biology / Genetics","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83030360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 2022: Palmitate promotes breast cancer progression in vitro through induction of a senescent-like phenotype in fibroblasts","authors":"B. Harlow, Albert R. Davalos, A. Brenner, C. Jolly, S. Tiziani, S. Hursting, Linda A. Degraffenried","doi":"10.1158/1538-7445.AM2021-2022","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2022","url":null,"abstract":"","PeriodicalId":18754,"journal":{"name":"Molecular and Cellular Biology / Genetics","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82219471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract LB211: Epstein-Barr virus BART lncRNAs induceIKZF3/Aiolos to maintain EBV latency and promote tumorigenicity in nasopharyngeal carcinoma","authors":"Songtao He, Jiayan Liu, Honglin Chen","doi":"10.1158/1538-7445.AM2021-LB211","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-LB211","url":null,"abstract":"\u0000 Epstein-Barr virus (EBV) maintains latency in its associated tumors, including nasopharyngeal carcinoma (NPC), expressing very few viral proteins but abundant levels of noncoding RNAs (mainly EBERs and BARTs) in NPC cells. We found that IKZF3/Aiolos is a downstream target of BART lncRNAs in NPC cells. The functions of BART lncRNAs and IKZF3 in EBV latency and pathogenesis of NPC remain elusive. In this study, meta-analysis of eight EBV-associated studies showed that IKZF3/Aiolos was consistently upregulated in EBV-infected NPC cells. Our study further showed that transcription of IKZF3/Aiolos is highly upregulated in EBV-infected NPC cells and clinical tissue samples due to the action of EBV encoded BART lncRNAs, with IKZF3/Aiolos was expressed at higher levels in late stage (stage III & IV) NPC patients than in early stage (stage I & II) disease. Secondly, we found that IKZF3/Aiolos was upregulated in BART-activated NPC cells but downregulated in BART-knockdown NPC cells. In addition, this study further demonstrated that IKZF3/Aiolos modulates transcription of EBV BZLF1 and the cellular gene, LRIG1, to maintain EBV latency and promote NPC tumorigenesis in vitro and in vivo. Our results showed that the EBV lytic reactivator BZLF1 was upregulated in IKZF3/Aiolos knockout or Aiolos inhibitor-treated NPC cells. ChIP-qPCR, immunoprecipitation and immunofluorescence analyses further revealed that IKZF3/Aiolos induces H3K27 deacetylation to silence expression of BZLF1 and maintain EBV latency in NPC cells. Moreover, functional analyses and western blotting showed that IKZF3/Aiolos inhibited the tumor suppressor, LRIG1, to upregulate expression and phosphorylation of the cellular proto-oncogene Erb-B2 for NPC pathogenesis. Sphere- and colony-formation assays demonstrated that IKZF3/Aiolos enhances growth of NPC cells in vitro, and in vivo experiments further showed that IKZF3/Aiolos promotes tumorigenicity of NPC cells in NOD mice. Mechanically, we found that the expression of EBV lytic reactivator BZLF1 and cellular LRIG1 were negatively regulated by BART lncRNA/IKZF3/Aiolos regulatory machinery in NPC cells, while Erb-B2 was positively regulated, which indicated that IKZF3/Aiolos is a new biomarker for NPC and may lead to the development of novel diagnostic tests and treatments for NPC.\u0000 Citation Format: Songtao He, Jiayan Liu, Bobo Wing-Yee Mok, Sai Wah Tsao, Honglin Chen. Epstein-Barr virus BART lncRNAs induce IKZF3/Aiolos to maintain EBV latency and promote tumorigenicity in nasopharyngeal carcinoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3748.","PeriodicalId":18754,"journal":{"name":"Molecular and Cellular Biology / Genetics","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81556169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 2452: Metformin administration in hypoglycemia compromises cancer cell viability in glioblastoma initiating cells","authors":"F. Cianci, R. Cazzoli, I. Verduci, S. Minucci, M. Mazzanti","doi":"10.1158/1538-7445.AM2021-2452","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2452","url":null,"abstract":"","PeriodicalId":18754,"journal":{"name":"Molecular and Cellular Biology / Genetics","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82500917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 2238: A novel comprehensive breakpoint-targeted assay for clinically actionable RNA fusions and aberrant RNAs in solid tumors","authors":"F. Lopez-Diaz, S. Rivera, Chen-Yin Ou, C. Magnan, Brad B Thomas, T. Gyuris, Y. Mou, Segun Jung, Madhuri Paul, Forrest Blocker, Shari Brown, Jacqueline K. Lekostaj, Ryan P. Bender, S. Agersborg, L. Weiss, V. Funari","doi":"10.1158/1538-7445.AM2021-2238","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2238","url":null,"abstract":"","PeriodicalId":18754,"journal":{"name":"Molecular and Cellular Biology / Genetics","volume":"128 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82911718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 2106: Combined deacetylase and bromodomain inhibition downregulates ERCC2 and suppresses growth of metastatic colon cancer cells","authors":"Sabeeta Kapoor, Trace Gustafson, Mutian Zhang, Ying-Shiuan Chen, Jia Li, Nhung Nguyen, J. E. Pérez, W. Dashwood, P. Rajendran, R. Dashwood","doi":"10.1158/1538-7445.AM2021-2106","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2106","url":null,"abstract":"DNA repair genes have potential clinical value in predicting cancer prognosis and treatment outcomes. Nucleotide excision repair (NER) proteins like ERCC2 play a critical role in maintaining genome integrity by recognizing and unwinding DNA at sites of damage1.Aberrant expression of ERCC2 alters NER capacity, influencing treatment outcomes2. The current investigation examined the expression of ERCC2 following epigenetic combination treatment in colorectal cancer (CRC) cells and preclinical models. Attention was drawn to ERCC2 based on three observations. First, from online databases, when ERCC2 was overexpressed in colon tumors the corresponding CRC patients had reduced overall survival3. Second, ERCC2 was the most highly downregulated gene when dietary histone deacetylase 3 (HDAC3) inhibitor sulforaphane (SFN) was combined withJQ1, an inhibitor of the bromodomain and extra terminal domain family, in human colon cancer cells and in colon polyps from the polyposis in rat colon (Pirc) model4. Third, as reported here for the first time, RNA-seq analyses of Pirc colon polyps from rats treated withJQ1 and the SFN analog 6-SFN5 identified Ercc2 as the most highly downregulated gene. RNA-seq data were corroborated by RT-qPCR and immunoblotting experiments. There is much interest in combination approaches that target epigenetic ‘readers, writers, and erasers9 that are deregulated in cancer and other pathologies. The current work identified promising second-generation inhibitors with enhanced synergy and antitumor efficacy, especially in metastatic cells cultured in three-dimensions. Drug combinations decreased HDAC3, BRD4 and ERCC2 expression, while DNA damage and apoptosis markers were increased both in spheroids and in a mouse xenograft model. This investigation has potential clinical relevance for the identification of robust biomarkers that predict enhanced antitumor outcomes in CRC patients.1. Gillet LC, Scharer OD. Molecular mechanisms of mammalian global genome nucleotide excision repair. Chem Rev 2006;106:253-76.2. Shuck SC, Short EA, Turchi JJ. Eukaryotic nucleotide excision repair: from understanding mechanisms to influencing biology. Cell Res 2008;18:64-72.3. Liu J et al., The Differential Expression of Core Genes in Nucleotide Excision Repair Pathway Indicates Colorectal Carcinogenesis and Prognosis. Biomed Res Int 2018;2018:9651320.4. Rajendran P et al., Acetylation of CCAR2 establishes a BET/BRD9 acetyl switch in response to combined deacetylase and bromodomain inhibition. Cancer Res 2019;79:918-27.5. Rajendran Pet al., HDAC turnover, CtIP acetylation and dysregulated DNA damage signaling in colon cancer cell treated with sulforaphane and related dietary isothiocyanates. Epigenetics 2013;8:612-23. Citation Format: Sabeeta Kapoor, Trace Gustafson, Mutian Zhang, Ying-Shiuan Chen, Jia Li, Nhung Nguyen, Jorge Enrique Perez, Wan Mohaiza Dashwood, Praveen Rajendran, Roderick Dashwood. Combined deacetylase and bromodomain inhibition downregulates ","PeriodicalId":18754,"journal":{"name":"Molecular and Cellular Biology / Genetics","volume":"61 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90828584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}