Review
Biochemistry & Molecular Biology
Sarah S. Wang, Jihao Xu, Keely Y. Ji, Chang-Il Hwang
Summary: Pancreatic cancer, particularly pancreatic ductal adenocarcinoma (PDA), is a significant cause of cancer-related deaths in the United States. While genetic mutations driving PDA initiation and progression have been identified, the mechanisms underlying PDA metastasis remain elusive. It is suggested that epigenetic fluctuations may play a critical role in driving PDA metastasis.
Article
Multidisciplinary Sciences
Zhenhui Zhong, Suhua Feng, Sascha H. Duttke, Magdalena E. Potok, Yiwei Zhang, Javier Gallego-Bartolom, Wanlu Liu, Steven E. Jacobsen
Summary: DNA methylation influences chromatin accessibility, particularly in heterochromatin, in plants. Different sequence contexts of DNA methylation interact with each other, and methylation can impact chromatin structure through mechanisms other than transcription. Increased chromatin accessibility is associated with enhanced long-range chromatin interactions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Oncology
Yuhao Zhao, Mao Yang, Shijia Wang, Sk Jahir Abbas, Junzhe Zhang, Yongsheng Li, Rong Shao, Yingbin Liu
Summary: This review focuses on the mechanistic insights of DNA, histone, and RNA methylation in regulating the progression of pancreatic cancer. The roles of methylation regulators in modulating gene expression associated with cell proliferation, invasion, and apoptosis are discussed. Recent clinical trials on methylation drug targeting are also explored. Understanding the novel regulatory mechanisms of methylation modification may offer alternative opportunities to improve therapeutic efficacy in combating this devastating disease.
FRONTIERS IN ONCOLOGY
(2022)
Review
Environmental Sciences
Sherihan G. AbdelHamid, Aya A. Refaat, Anthony M. Benjamin, Laila A. Elmawardy, Lougine A. Elgendy, Mark M. Manolly, Nada Abd Elmaksoud, Nourhan Sherif, Nadia M. Hamdy
Summary: The COVID-19 pandemic has led to drastic postinfection complications with interindividual variations, prompting research on the impact of epigenetic modulation on infection susceptibility and outcome. Studies suggest that viral microRNAs and host DNA methylation and chromatin remodeling may play crucial roles in influencing the severity and outcome of the disease.
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2021)
Article
Oncology
Olga A. Sukocheva, Elena Lukina, Markus Friedemann, Mario Menschikowski, Albert Hagelgans, Gjumrakch Aliev
Summary: This article discusses recent advances in the epigenetic regulation of endocrine drug resistance and evaluates novel anti-resistance strategies. It has been found that epigenetic mechanisms can effectively silence ER expression and facilitate the development of endocrine resistance in breast cancer cells. Targeted inhibition of specific epigenetic tools can recover ER expression and increase sensitivity to anti-estrogens, preventing the selection of resistant cells and cancer stem cell survival.
SEMINARS IN CANCER BIOLOGY
(2022)
Review
Medicine, Research & Experimental
Felix Recillas-Targa
Summary: Cancer is a complex disease caused by genetic and epigenetic alterations in cell division control. Understanding the origin and evolution of tumorigenic processes through cancer genomics and epigenomics has advanced our knowledge of the molecular causes of cancer. The interplay between genetic and epigenetic mutations, as well as their interaction with environmental factors such as the microbiome, influences cellular metabolism and proliferation rates, leading to tumorigenesis. Integrating and improving our understanding of these processes can enhance cancer diagnosis, prognosis, and genetic and epigenetic therapies.
ARCHIVES OF MEDICAL RESEARCH
(2022)
Editorial Material
Biochemistry & Molecular Biology
Eleni Skourti, Paraminder Dhillon
Summary: This Special Issue of The FEBS Journal, Cancer Epigenetics, features a collection of review articles that focus on the functions of a broad spectrum of epigenetic modulators in cancer. The topics explored in these articles range from the roles of transposable elements and chromatin architecture in cancer, to the effects of altered epigenetics on transcription and advanced cancer cell phenotypes. The potential of epigenetics for targeted cancer therapeutics is also discussed.
Review
Oncology
Francisco Gimeno-Valiente, Gerardo Lopez-Rodas, Josefa Castillo, Luis Franco
Summary: This review focuses on the interconnections between epigenetics and alternative splicing in the development of cancer. It discusses the mechanisms involved in these interconnections and the potential diagnostic and therapeutic tools that can be derived from them. The reversible nature of epigenetic alterations and the possibility of correcting aberrant alternative splicing offer promising therapeutic possibilities for cancer treatment.
Article
Oncology
Harumi Yamada, Hideyuki Takeshima, Ryoji Fujiki, Satoshi Yamashita, Shigeki Sekine, Takayuki Ando, Naoko Hattori, Atsushi Okabe, Takaki Yoshikawa, Kazutaka Obama, Hitoshi Katai, Atsushi Kaneda, Toshikazu Ushijima
Summary: The CpG island methylator phenotype (CIMP) is associated with prognosis and drug sensitivity in multiple cancer types. This study demonstrates that mutations in the SWI/SNF chromatin remodeling complex, particularly ARID1A, are associated with CIMP induction in gastric cancer, as well as in uterine endometrial and colorectal cancers. The loss of ARID1A function causes aberrant DNA methylation and is likely a potential mechanism for CIMP induction.
Review
Oncology
Chitra Thakur, Yiran Qiu, Yao Fu, Zhuoyue Bi, Wenxuan Zhang, Haoyan Ji, Fei Chen
Summary: Breast cancer is the most commonly diagnosed cancer in women worldwide, and factors such as delayed presentation, late stage at diagnosis, limited treatment options, metastasis, and relapse contribute to high mortality rates. The development and progression of breast cancer involve complex genetic and epigenetic alterations, influenced by external environmental factors and internal cellular microenvironmental cues. Understanding the gene-environment interactions in breast cancer through a multidisciplinary approach is crucial. Epigenetic modifications, being reversible and influenced by external and intrinsic stimuli, offer potential avenues for designing effective therapies for breast cancer.
FRONTIERS IN ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Eshaan Patnaik, Chikezie Madu, Yi Lu
Summary: Epigenetics plays a crucial role in gene regulation and tumor development. DNA methylation inhibitors and histone deacetylase inhibitors can restore normal gene expression and be effective against cancer. Understanding epigenetic modifications and utilizing inhibitors offer new possibilities for cancer research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Chaithanya Ganji, Batoul Farran
Summary: This review focuses on dysregulated genes associated with epigenetic mechanisms in pancreatic cancer progression and resistance, as well as current clinical trials for epigenetic drugs. Combining epigenetic drugs with targeted therapies might represent a promising approach for treating pancreatic cancer.
DRUG DISCOVERY TODAY
(2022)
Article
Biology
Samuel N. Bogan, Marie E. Strader, Gretchen E. Hofmann
Summary: This study investigates the effects of DNA methylation on gene expression and splicing in the larvae of the purple sea urchin. It finds that differential gene body methylation has stronger effects on gene expression among genes with poorly accessible transcriptional start sites, and the baseline transcript abundance influences the direction of this effect. Considering the interactions between methylation and chromatin accessibility, the transcriptional responses to maternal conditioning are significantly increased, suggesting that the relationship between methylation and gene regulation is partially explained by chromatin state.
Review
Genetics & Heredity
Sonam Tulsyan, Mehreen Aftab, Sandeep Sisodiya, Asiya Khan, Atul Chikara, Pranay Tanwar, Showket Hussain
Summary: The global cancer cases and mortality rates are increasing, and efficient biomarkers are needed for accurate screening and diagnosis. Alterations in epigenetic marks may serve as potential biomarkers for early cancer detection. This review discusses the key epigenetic mechanisms and their deregulation in cancer etiology, exploring the future prospects of cancer precision medicine.
FRONTIERS IN GENETICS
(2022)
Review
Cell Biology
Rodrigo Villasenor, Tuncay Baubec
Summary: Nucleosomes are basic structures used to package genetic information, subject to diverse chemical modifications. These modifications serve as interaction hubs for nuclear proteins, ensuring correct deposition to the genome. The regulation of chromatin marks relies on coordinated activities of writer, eraser, and reader enzymes, often depending on complex multicomponent regulatory circuits.
CURRENT OPINION IN CELL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Jeremy Guillot, Chloe Dominici, Adrien Lucchesi, Huyen Thi Trang Nguyen, Angelique Puget, Melanie Hocine, Martha M. Rangel-Sosa, Milesa Simic, Jeremy Nigri, Fabienne Guillaumond, Martin Bigonnet, Nelson Dusetti, Jimmy Perrot, Jonathan Lopez, Anders Etzerodt, Toby Lawrence, Pierre Pudlo, Florence Hubert, Jean-Yves Scoazec, Serge A. van de Pavert, Richard Tomasini, Sophie Chauvet, Fanny Mann
Summary: This study utilized 3D imaging to analyze the sympathetic innervation in a mouse model of pancreatic ductal adenocarcinoma (PDAC) and found that sympathectomy aggravates cancer progression.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Michal Antoszczak, Sebastian Muller, Tatiana Caneque, Ludovic Colombeau, Nelson Dusetti, Patricia Santofimia-Castano, Christine Gaillet, Alain Puisieux, Juan Lucio Iovanna, Raphael Rodriguez
Summary: Persisting cancer cells are resistant to therapy and can adopt a drug-tolerant state through epithelial-mesenchymal plasticity. This study synthesized complex small molecule chimeras that accumulate in lysosomes and induce ferroptosis in drug-tolerant pancreatic cancer cells. The findings pave the way for the development of new cancer medicines targeting active ferroptosis.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Yunfang Xiong, Ran Ke, Qingyu Zhang, Wenjun Lan, Wanjun Yuan, Karol Nga Ieng Chan, Tom Roussel, Yifan Jiang, Jing Wu, Shuai Liu, Alice Sze Tsai Wong, Joong Sup Shim, Xuanjun Zhang, Ruiyu Xie, Nelson Dusetti, Juan Iovanna, Nagy Habib, Ling Peng, Leo Tsz On Lee
Summary: This study reports the effective modulation of a GPCR for cancer treatment using small activating RNAs (saRNAs) for the first time. The saRNAs promote the expression of MAS1, a GPCR that counteracts cancer cell proliferation and migration. By enhancing MAS1 expression, these saRNAs suppress tumorigenesis and inhibit tumor progression in multiple cancer models. This research not only provides a new strategy for cancer therapy by targeting the renin-angiotensin system, but also offers a new avenue to modulate GPCR signaling through RNA activation.
Article
Biology
Patricia Santofimia-Castano, Can Huang, Xi Liu, Yi Xia, Stephane Audebert, Luc Camoin, Ling Peng, Gwen Lomberk, Raul Urrutia, Philippe Soubeyran, Jose Luis Neira, Juan Iovanna
Summary: Mutations or treatment with the NUPR1 inhibitor ZZW-115 can inhibit the activity of PARP1 and induce cell death. Treatment with ZZW-115 or genetic inactivation of NUPR1 leads to mitochondrial catastrophe, which can be partially rescued by olaparib and NAD(+) precursor nicotinamide mononucleotide.
COMMUNICATIONS BIOLOGY
(2022)
Article
Gastroenterology & Hepatology
Raphael Rapetti-Mauss, Jeremy Nigri, Camille Berenguier, Pascal Finetti, Sarah Simha Tubiana, Bonnie Labrum, Benoit Allegrini, Bernard Pellissier, Georgios Efthymiou, Zainab Hussain, Corinne Bousquet, Nelson Dusetti, Francois Bertucci, Helene Guizouarn, Patricia Melnyk, Franck Borgese, Richard Tomasini, Olivier Soriani
Summary: This study reveals that ion channel SK2 plays a role in intercellular communication in pancreatic ductal adenocarcinoma (PDAC). Stimulation of SK2 by cues from cancer-associated fibroblasts (CAFs) leads to the activation of the integrin-epidermal growth factor receptor (EGFR)-AKT signaling pathway, promoting cancer cell invasiveness and metastasis formation. The formation of the signaling hub involving SK2 and AKT requires the sigma-1 receptor chaperone. Targeting the sigma-1 receptor with pharmacological approaches inhibits tumor progression and prolongs overall survival in mice.
Letter
Gastroenterology & Hepatology
Nicolas Fraunhoffer, Brice Chanez, Carlos Teyssedou, Juan L. Iovanna, Emmanuel Mitry, Nelson J. Dusetti
Article
Gastroenterology & Hepatology
Melinda Wang, Frank Ulrich Weiss, Xiaojia Guo, Thomas Kolodecik, Jan Philipp Bewersdorf, Loren Laine, Markus M. Lerch, Gary Desir, Fred S. Gorelick
Summary: Severe acute pancreatitis is associated with high morbidity and mortality rates. Plasma renalase levels decrease significantly in a murine acute pancreatitis model. This study aimed to investigate the levels of plasma renalase in hospitalized acute pancreatitis patients to determine if similar phenomenon occurs in humans.
Article
Cell Biology
Yizeng Yang, Dharmendra Bhargava, Xiao Chen, Taicheng Zhou, Gizem Dursuk, Wenpeng Jiang, Jinshen Wang, Zhen Zong, Sharyn I. Katz, Gwen A. Lomberk, Raul A. Urrutia, Jonathan P. Katz
Summary: In non-transformed human squamous epithelial cells, the decision of whether to arrest or undergo apoptosis in response to stress is mediated by the interaction between p53 and the zinc-finger transcription factor KLF5. The levels of cellular stress determine the specific outcome, with moderate stress leading to cell survival and severe stress resulting in apoptosis.
CELL DEATH & DISEASE
(2023)
Article
Multidisciplinary Sciences
Charlie Saillard, Flore Delecourt, Benoit Schmauch, Olivier Moindrot, Magali Svrcek, Armelle Bardier-Dupas, Jean Francois Emile, Mira Ayadi, Vinciane Rebours, Louis de Mestier, Pascal Hammel, Cindy Neuzillet, Jean Baptiste Bachet, Juan Iovanna, Nelson Dusetti, Yuna Blum, Magali Richard, Yasmina Kermezli, Valerie Paradis, Mikhail Zaslavskiy, Pierre Courtiol, Aurelie Kamoun, Remy Nicolle, Jerome Cros
Summary: This study developed a deep learning model called PACpAInt to predict the tumor tissue and subtypes of pancreatic adenocarcinoma (PDAC) using transcriptomic data. The model identified PDAC heterogeneity and revealed the presence of different tumor subtypes and transitional states during PDAC evolution.
NATURE COMMUNICATIONS
(2023)
Article
Medicine, General & Internal
Nicolas A. Fraunhoffer, Aura I. Moreno Vega, Anala Meilerman Abuelafia, Marie Morvan, Emilie Lebarbier, Tristan Mary-Huard, Michael Zimmermann, Gwen Lomberk, Raul Urrutia, Nelson Dusetti, Yuna Blum, Remy Nicolle, Juan Iovanna
Summary: Using epigenomic inhibitors to reset gene expression patterns in pancreatic tumors shows promise in developing new therapies for pancreatic cancer.
Article
Medicine, General & Internal
Abdessamad El Kaoutari, Nicolas A. Fraunhoffer, Luc Camoin, Yolande Berthois, Odile Gayet, Julie Roques, Martin Bigonnet, Claire Bongrain, Joseph Ciccolini, Juan L. Iovanna, Nelson J. Dusetti, Philippe Soubeyran
Summary: Through specific proteomic tools and bioinformatics analysis, we established the ubiquitin dependent proteome of 60 PDAC, identifying 38 ubiquitination site profiles correlated with tumor phenotype and having prognostic capabilities. These findings have potential application in predicting chemotherapy response and personalized treatment in clinical settings.
Article
Multidisciplinary Sciences
Gabriela Reyes-Castellanos, Nadine Abdel Hadi, Scarlett Gallardo-Arriaga, Rawand Masoud, Julie Garcia, Sophie Lac, Abdessamad El Kaoutari, Tristan Gicquel, Melanie Planque, Sarah-Maria Fendt, Laetitia Karine Linares, Odile Gayet, Fabienne Guillaumond, Nelson Dusetti, Juan Iovanna, Alice Carrier
Summary: Pancreatic ductal adenocarcinoma is a highly fatal cancer. A study found that mitochondrial respiration in primary human PDAC cells relies on fatty acid oxidation for energy production. The use of perhexiline, an inhibitor of fatty acid oxidation, in combination with chemotherapy showed promising results in inhibiting PDAC cell growth in vitro and in vivo. Molecular analysis revealed the importance of the CPT1C isoform in the response to perhexiline and its association with better prognosis in PDAC patients.
Article
Oncology
Ellis Michiels, Hediel Madhloum, Silke Van Lint, Nouredin Messaoudi, Rastislav Kunda, Sandrina Martens, Philippe Giron, Catharina Olsen, Pierre Lefesvre, Nelson Dusetti, Leila EL Mohajer, Richard Tomasini, Lukas J. A. C. Hawinkels, Farah Ahsayni, Remy Nicolle, Tatjana Arsenijevic, Christelle Bouchart, Jean-Luc Van Laethem, Ilse Rooman
Summary: This study identifies two subtypes of pancreatic cancer and reveals spatial phenotypes within tumors through analysis of mRNA panels. These findings are important for understanding tumor heterogeneity and guiding therapeutic approaches.
JOURNAL OF PATHOLOGY
(2023)
Review
Immunology
Juliane Glaubitz, Saeedeh Asgarbeik, Rabea Lange, Hala Mazloum, Hager Elsheikh, Frank Ulrich Weiss, Matthias Sendler
Summary: Acute pancreatitis is a common inflammatory disease of the gastrointestinal tract and is increasingly diagnosed in hospitalized patients. It often progresses to chronic pancreatitis over time, with immune response playing a significant role in determining the severity and course of the disease. The mortality rate of acute pancreatitis is high, caused by excessive inflammation or inhibition of bacterial defense mechanisms leading to severe necrotizing pancreatitis. Targeting the immune response is the most promising therapeutic strategy, but the complexity of the immune response and the risk of chronic disease development limit treatment interventions.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Young-In Chi, Davin R. Jensen, Brian C. Smith, Brian F. Volkman, Angela J. Mathison, Gwen Lomberk, Michael T. Zimmermann, Raul Urrutia
Summary: This study investigates the functional significance of various variants of uncertain significance in the EHMT1 protein. By combining traditional tools with computational methods, the researchers were able to classify the variants into different categories based on their structural and dynamic properties. The damaging variants were found to be located near important functional sites. This study improves upon conventional tools for variant interpretation and provides a molecular mechanism for variant dysfunction.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Review
Oncology
Xinru Zhou, Yin Jia, Chuanbin Mao, Shanrong Liu
Summary: Small extracellular vesicles (sEVs), such as exosomes, have emerged as crucial targets for liquid biopsy and promising drug delivery vehicles in tumor progression. They can serve as biomarkers for tumor diagnosis and as drug carriers for cancer treatment.
Article
Oncology
Ruochan Chen, Ju Zhu, Xiao Zhong, Jie Li, Rui Kang, Daolin Tang
Summary: The interplay between autophagy and apoptosis plays a crucial role in tumorigenesis and cancer therapy, with HMGB1 serving as a key regulator in these processes.
Article
Oncology
Zongfu Pan, Xixuan Lu, Tong Xu, Jinming Chen, Lisha Bao, Ying Li, Yingying Gong, Yulu Che, Xiaozhou Zou, Zhuo Tan, Ping Huang, Minghua Ge
Summary: This study uncovered the emerging role of HN1 in promoting dedifferentiation of anaplastic thyroid cancer (ATC) cells. HN1 negatively regulated the thyroid differentiation markers and had an inhibitory effect on the transcriptional activation of CTCF, thereby influencing the chromatin accessibility of thyroid differentiation genes.
Article
Oncology
Yi Qin, Shengjun Xiong, Jun Ren, Gautam Sethi
Summary: Autophagy plays an important regulatory role in glioblastoma, and its dysregulation can lead to drug resistance and radioresistance. It also affects stem cell characteristics, overall growth, and metastasis. Therefore, autophagy is a promising target for glioblastoma therapy.
Article
Oncology
Katsuya Nagaoka, Xuewei Bai, Dan Liu, Kevin Cao, Joud Mulla, Chengcheng Ji, Hongze Chen, Muhammad Azhar Nisar, Amalia Bay, William Mueller, Grace Hildebrand, Jin-Song Gao, Shaolei Lu, Hiroko Setoyama, Yasuhito Tanaka, Jack R. Wands, Chiung-Kuei Huang
Summary: This study found that serum 2-OG levels in cholangiocarcinoma patients are associated with the effectiveness of chemotherapy. Patients with progressive disease showed significantly higher levels of serum 2-OG compared to stable disease and partial response patients. The study also revealed that overexpression of ASPH mimics the effects of 2-OG, and knockdown of ASPH improves chemotherapy. Targeting ASPH enhances the effects of chemotherapy by modulating ATM and ATR, two key regulators of DDRs.