Review
Cell Biology
Ruozhu Yang, Yi Han, Xinyu Guan, Yue Hong, Jiahao Meng, Shirong Ding, Qian Long, Wenjun Yi
Summary: TERT is an essential enzyme responsible for telomere maintenance and genome stability. In breast cancer, the overactivation of hTERT plays a critical role in tumor initiation and progression. Understanding the mechanisms of hTERT activation in cancer could lead to improved understanding of the disease and the development of more effective treatment strategies.
CELL COMMUNICATION AND SIGNALING
(2023)
Review
Biochemistry & Molecular Biology
Anna A. Plyasova, Dmitry D. Zhdanov
Summary: Alternative splicing of hTERT pre-mRNA regulates telomerase activity and determines cell functions. In addition to telomerase activity regulation, alternative splicing provides cells with splice variants that may have alternative biological activities.
Article
Chemistry, Medicinal
Martina Menna, Francesco Fiorentino, Biagina Marrocco, Alessia Lucidi, Stefano Tomassi, Domenica Cilli, Mauro Romanenghi, Matteo Cassandri, Silvia Pomella, Michele Pezzella, Donatella Del Bufalo, Mohammad Salik Zeya Ansari, Nevena Tomasevic, Milan Mladenovic, Monica Viviano, Gianluca Sbardella, Rossella Rota, Daniela Trisciuoglio, Saverio Minucci, Andrea Mattevi, Dante Rotili, Antonello Mai
Summary: Chemical modifications of LSD1 led to highly active and selective inhibitors, which showed antiproliferative effects and gene expression regulation in leukemia cells. The inhibition of LSD1 demonstrated a crucial role in solid tumor cells, suggesting no added value for simultaneous G9a inhibition.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Nao Yamakado, Satoshi Okuda, Kei Tobiume, Ryo Uetsuki, Shigehiro Ono, Kuniko Mizuta, Takayuki Nakagawa, Tomonao Aikawa
Summary: Oral squamous cell carcinoma (SCC) is a tumor with bidirectional cell plasticity, and the chemical LSD1 inhibitor can induce EMT in the cell line OM-1. The induction of EMT is associated with the upregulation of EMT-TFs ZEB1 and Snail, as well as increased histone H3 methylation in the regulatory regions of ZEB1.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Catherine M. Mills, Jonathan Turner, Ivett C. Pina, Kathleen A. Garrabrant, Dirk Geerts, Andre S. Bachmann, Yuri K. Peterson, Patrick M. Woster
Summary: LSD1, an epigenetic regulator, is an oncogenic accomplice in MYCN-expressing neuroblastoma. We report 3 novel scaffolds for reversible LSD1 inhibition and found one of them to be highly potent and able to increase an important modification mark in cells. Combination treatment with bortezomib also showed a synergistic effect.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Ifra Mushtaq, Gh Rasool Bhat, Bilal Rah, Syed Besina, Sheikh Zahoor, Muneer A. Wani, Mubashir A. Shah, Sadaf Bashir, Muzamil Farooq, Rafiq A. Rather, Dil Afroze
Summary: Genetic instabilities and telomere dysfunction play a crucial role in cancer development, especially gastric cancer. This study evaluates the clinical implications of c-Myc, hTERT expression, and telomere length, shedding light on their significance in gastric cancer progression.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Li Tao, Wei Zhang, Yaxin Zhang, Mei Zhang, Yueying Zhang, Xing Niu, Qing Zhao, Zhenxing Liu, Yuyin Li, Aipo Diao
Summary: The study showed that caffeine can promote the expression of TERT to extend telomere length and prevent cellular senescence. In animal studies, caffeine also reversed the decline in organ index and improved tissue structure in aging mice. These results suggest that caffeine-containing foods can delay cellular senescence and aging through the expression of TERT.
Article
Pharmacology & Pharmacy
Baohui Yuan, He Liu, Xiaohua Pan, Xiaoliang Dong, Le-Feng Qu, Jia Sun, Li-Long Pan
Summary: LSD1 plays a crucial role in neointima formation, and its overexpression is associated with neointima formation. Knockdown of LSD1 significantly reduces neointima formation and inhibits platelet-derived growth factor-induced VSMC proliferation. Moreover, LSD1 overexpression exhibits opposite effects in vivo and in vitro.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Bo Wang, Jianping Jiang, Yun Zhang, Yingying Shen, Liqiang Wu, Siqi Tang, Shengyun Lin
Summary: The study investigated the use of plant extracts as potential therapeutic strategies for cancer treatment, particularly in high-risk MDS patients. The newly extracted coumarin HDE from Oldenlandia diffusa Willd efficiently inhibited MDS cell proliferation and induced apoptosis, with the combination of HDE and BIIB021 showing synergistic antitumor effects on SKM-1 cells, providing a novel therapeutic combination for higher-risk MDS.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2021)
Article
Multidisciplinary Sciences
Mattie J. Casey, Alexandra M. Call, Annika V. Thorpe, Cicely A. Jette, Michael E. Engel, Rodney A. Stewart
Summary: Lsd1/Kdm1a functions as both a histone demethylase enzyme and a scaffold for assembling chromatin modifier and transcription factor complexes to regulate gene expression during embryogenesis. Our analysis of zebrafish lsd1/kdm1a mutants reveals that Lsd1's scaffolding function, mediated by its SNAG-binding domain, is required for repression of gene expression, including gfi1 and snai1/2, through a negative feedback loop.
Article
Immunology
Jingjing Wang, Zhikai Wu, Xingyi Zhu, Peixuan Li, Yiwu Fu, Xia Wang, Youpeng Sun, Ershun Zhou, Zhengtao Yang
Summary: The study demonstrates the important regulatory roles of LSD1 in LPS-induced mastitis and the inhibitory effects of GSK-LSD1 on LSD1 activity, leading to reduced inflammatory response and tissue damage. The inhibition of LSD1 results in increased histone H3K4me2 and H3K9me2 levels, and suppression of NF-kappa B signaling and cytokine production in mammary gland. These findings suggest LSD1 as a potential regulator of inflammation and provide insights into epigenetic control mechanisms in inflammation.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Caixia He, Xiaorui Zhang, Jin Li, Conglin Dai, Siqi Wang, Can Dai, Sicong Zeng
Summary: Telomerase activity is not essential for the properties of mesenchymal stem cells (MSCs), but it is required for community maintenance and migration of placental mesenchymal stem cells (PMSCs).
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biology
Hueng-Chuen Fan, Fung-Wei Chang, Jeng-Dau Tsai, Kao-Min Lin, Chuan-Mu Chen, Shinn-Zong Lin, Ching-Ann Liu, Horng-Jyh Harn
Summary: Telomeres cap the ends of eukaryotic chromosomes and are essential for genome protection and replication. The maintenance of telomere length is regulated by various factors and dysfunctions in telomere maintenance and telomerase activation are associated with diseases, particularly cancer. Understanding the molecular mechanisms behind telomere length regulation and protection is crucial for future therapeutic opportunities.
Article
Oncology
Olivier Adotevi, Dewi Vernerey, Pascale Jacoulet, Aurelia Meurisse, Caroline Laheurte, Hamadi Almotlak, Marion Jacquin, Vincent Kaulek, Laura Boullerot, Marine Malfroy, Emeline Orillard, Guillaume Eberst, Aurelie Lagrange, Laure Favier, Marie Gainet-Brun, Ludovic Doucet, Luis Teixeira, Zineb Ghrieb, Anne-Laure Clairet, Yves Guillaume, Marie Kroemer, Didier Hocquet, Melanie Moltenis, Samuel Limat, Elisabeth Quoix, Celine Mascaux, Didier Debieuvre, Christine Fagnoni-Legat, Christophe Borg, Virginie Westeel
Summary: The purpose of this study was to test the safety, immunogenicity, and efficacy of UCPVax vaccine in patients with metastatic non-small-cell lung cancer. The results showed that UCPVax vaccine was highly immunogenic and safe, and achieved interesting 1-year survival rate in advanced NSCLC patients.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Review
Oncology
Miguel Angel Gonzalez-Moles, Eloisa Moya-Gonzalez, Alberto Garcia-Ferrera, Paola Nieto-Casado, Pablo Ramos-Garcia
Summary: TERT protein overexpression in oral cancer is significantly associated with poor survival and has prognostic value. This systematic review and meta-analysis, based on 21 studies and 1698 patients, support the immunohistochemical assessment of TERT overexpression as a new indicator for prognostic evaluation of oral squamous cell carcinoma.
Article
Biochemistry & Molecular Biology
Xiaotian Yuan, Ninni Mu, Na Wang, Klas Straat, Anastasios Sofiadis, Yanxia Guo, Adam Stenman, Kailin Li, Guanghui Cheng, Lu Zhang, Feng Kong, Lars Ekblad, Johan Wennerberg, Inga-Lena Nilsson, C. Christofer Juhlin, Catharina Larsson, Dawei Xu
Article
Cell Biology
Guoliang Wang, Yi Huang, Feilong Yang, Xiaojun Tian, Kun Wang, Li Liu, Yidong Fan, Xiaofeng Li, Luchao Li, Benkang Shi, Yichang Hao, Chuanyou Xia, Qingsheng Nie, Yue Xin, Zhenfeng Shi, Lulin Ma, Dawei Xu, Cheng Liu
Article
Biochemistry & Molecular Biology
Yanxia Guo, Xiaotian Yuan, Kailin Li, Mingkai Dai, Lu Zhang, Yujiao Wu, Chao Sun, Yuan Chen, Guanghui Cheng, Cheng Liu, Klas Straat, Feng Kong, Shengtian Zhao, Magnus Bjorkholm, Dawei Xu
CELL DEATH AND DIFFERENTIATION
(2020)
Review
Chemistry, Medicinal
Xiaotian Yuan, Mingkai Dai, Dawei Xu
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Cheng Liu, Li Liu, Kun Wang, Xiao-Feng Li, Li-Yuan Ge, Run-Zhuo Ma, Yi-Dong Fan, Lu-Chao Li, Zheng-Fang Liu, Min Qiu, Yi-Chang Hao, Zhen-Feng Shi, Chuan-You Xia, Klas Straat, Yi Huang, Lu-Lin Ma, Dawei Xu
Article
Biochemistry & Molecular Biology
Jenny Dahlstrom, Chuanyou Xia, Xiangling Xing, Xiaotian Yuan, Magnus Bjorkholm, Dawei Xu
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2020)
Article
Oncology
Xiangling Xing, Ninni Mu, Xiaotian Yuan, Na Wang, C. Christofer Juhlin, Klas Straat, Catharina Larsson, Dawei Xu
Article
Biochemistry & Molecular Biology
Li-Na Wang, Li Wang, Guanghui Cheng, Mingkai Dai, Yunhai Yu, Guoxin Teng, Jingjie Zhao, Dawei Xu
Summary: The study found that TERT overexpression inhibits SDC-1 expression in cervical cancer cells, affecting HPV invasion. Additionally, in females without HPV infection, telomeres in cervical epithelial cells were longer, and there were significant differences in TERT gene SNPs compared to those in the hrHPV group.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Oncology
Tiantian Liu, Jiansheng Wang, Yuchen Xiu, Yujiao Wu, Dawei Xu
Summary: The study reveals the presence of highly drifted DNAm age (HDDA) in cancer tissues, especially in thyroid carcinomas, with HDDA significantly associated with tumor cell dedifferentiation and poor patient outcomes. HDDA may serve as a new prognostic factor for thyroid carcinomas.
Article
Oncology
Xiangling Xing, Ninni Mu, Xiaotian Yuan, Na Wang, C. Christofer Juhlin, Klas Straat, Catharina Larsson, Shi Yong Neo, Dawei Xu
Summary: GABPB1 plays an oncogenic role in activating TERT gene expression, but also has tumor-suppressive functions in thyroid cancer. Targeting GABPB1 for cancer therapy should be cautious.
Article
Oncology
Jing Wang, Mingkai Dai, Xiangling Xing, Xing Wang, Xin Qin, Tao Huang, Zhiqing Fang, Yidong Fan, Dawei Xu
Summary: Research has shown a close connection between telomerase activity score and characteristics like tumor stemness, proliferation, and activation of oncogenic signaling pathways, revealing a potential biomarker for predicting patient outcomes and response to immunotherapy. Additionally, the telomerase component TCAB1 may act as a dispensable factor in telomerase function.
MOLECULAR ONCOLOGY
(2023)
Article
Medicine, Research & Experimental
Xin Qin, Jing Wang, Xing Wang, Tao Huang, Zhiqing Fang, Lei Yan, Yidong Fan, Dawei Xu
Summary: DNA helicases play a crucial role in maintaining genomic stability, and mutations in these genes can lead to genomic instability and cancer susceptibility. Interestingly, overexpression of DNA helicases is observed in certain cancers. In this study, genomic and molecular alterations in 12 important DNA helicases were analyzed across various types of cancers. The study revealed significant expression heterogeneity among these helicases, and tumors were classified into subtypes based on their DNA helicase score. The high DNA helicase score subtypes were associated with stemness, proliferation, oncogenic signaling, longer telomeres, more mutations, copy number alterations, and shorter survival. Furthermore, high DNA helicase scores were linked to sensitivity to chemo- and radio-therapies, as well as defects in DNA repair pathways like homologous recombination deficiency. Importantly, a potential DNA helicase inhibitor, Danusertib, was identified in this study. These findings highlight the dysregulation of DNA helicases in cancer and their potential as therapeutic targets.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Oncology
Xiaotian Yuan, Huiyang Yuan, Ning Zhang, Tiantian Liu, Dawei Xu
Summary: This article summarizes the mechanisms of telomerase activation and TERT gene induction in thyroid carcinomas, as well as their implications in thyroid cancer precision medicine.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Article
Endocrinology & Metabolism
Huiyang Yuan, Xin Qin, Qingya Yang, Li Liu, Zhiqing Fang, Yidong Fan, Dawei Xu
Summary: In clear cell renal cell carcinoma (ccRCC) patients, high expression of DKC1 is associated with shorter disease progression-free survival (PFS) in female but not male patients. In ccRCC patients treated with Sunitinib, female patients in the DKC1-high group have lower response rates and shorter PFS. DKC1 serves as an independent female-specific predictor for survival and Sunitinib efficacy.
BIOLOGY OF SEX DIFFERENCES
(2023)
Review
Oncology
Xiaotian Yuan, Mingkai Dai, Dawei Xu