Article
Multidisciplinary Sciences
Hong-Chieh Tsai, Han-Hsing Tsou, Chun-Chi Lin, Shao-Chen Chen, Hsiao-Wei Cheng, Tsung-Yun Liu, Wei-Shone Chen, Jeng-Kai Jiang, Shung-Haur Yang, Shih-Ching Chang, Hao-Wei Teng, Hsiang-Tsai Wang
Summary: Colorectal cancer is a well-known malignancy with high prevalence and poor 5-year survival, and a high-fat diet may increase the odds of developing this cancer. Acrolein plays a crucial role in oncogenic transformation through activation of the RAS/MAPK signaling pathway in colon tumorigenesis.
SCIENTIFIC REPORTS
(2021)
Article
Endocrinology & Metabolism
Priyanka Singh, Sanjay Kumar Bhadada, Ashutosh Kumar Arya, Uma Nahar Saikia, Naresh Sachdeva, Divya Dahiya, Jyotdeep Kaur, Maria Luisa Brandi, Sudhaker Dhanwada Rao
Summary: This study investigated the epigenetic-mediated mechanism of the PAX1 gene in sporadic parathyroid adenomas. The results revealed that the expression of PAX1 was significantly reduced in parathyroid adenomas, which was associated with hypermethylation in the promoter region and lower levels of histone modification. Treatment with a pharmacologic inhibitor led to the re-expression of the PAX1 gene. These findings provide insights into the epigenetic deregulation of PAX1 in parathyroid adenomas and have potential clinical and therapeutic implications for patients with PHPT.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Cell Biology
Tao Wei, Jin Li, Jian Zhang, Qi Zhang, Xiaoyu Liu, Qi Chen, Liang Wen, Ke Ma, Wen Chen, Jianhui Zhao, Cheng Zhang, Jinyan Huang, Yali Xie, Hao Qin, Danfeng Qian, Tingbo Liang
Summary: While Mettl3 has been shown to have oncogenic roles in hepatocellular carcinoma (HCC), its function in early HCC tumorigenesis is unclear. Mettl3 loss leads to hepatocyte homeostasis disruption and liver damage, accelerating liver tumorigenesis. Depletion of Mettl3 enhances liver tumor development, while overexpression of Mettl3 inhibits hepatocarcinogenesis. These findings suggest a stage-dependent tumor-suppressive role of Mettl3 in HCC initiation and progression.
Article
Gastroenterology & Hepatology
Rossella Tricarico, Jozef Madzo, Gabrielle Scher, Maya Cohen, Jaroslav Jelinek, Shinji Maegawa, Rajeswari Nagarathinam, Carly Scher, Wen-Chi Chang, Emmanuelle Nicolas, Michael Slifker, Yan Zhou, Karthik Devarajan, Kathy Q. Cai, Tim Kwok, Pamela Nakajima, Jinfei Xu, Pietro Mancuso, Valentina Doneddu, Luigi Bagella, Riley Williams, Siddharth Balachandran, Nicholas Maskalenko, Kerry Campbell, Xueying Ma, Israel Canadas, Julen Viana-Errasti, Victor Moreno, Laura Valle, Sergei Grivennikov, Iuliia Peshkova, Natalia Kurilenko, Aleksandra Mazitova, Ekaterina Koltsova, Hayan Lee, Martin Walsh, Reuben Duttweiler, Johnathan R. Whetstine, Timothy J. Yen, Jean-Pierre Issa, Alfonso Bellacosa
Summary: Aberrant DNA methylation is common in colorectal cancer (CRC), but the underlying mechanisms and pathological consequences are not well understood. In this study, disruption of the Tet1 and/or Tdg genes in mice resulted in increased size and invasive features of colonic adenomas. Furthermore, Tet1 and Tdg mutations led to global DNA hypomethylation and CpG island hypermethylation in colonic adenomas. The mutations also upregulated inflammatory, immune, and interferon response genes.
Article
Oncology
Jie Luo, Jie-Wei Chen, Jie Zhou, Kai Han, Si Li, Jin-Ling Duan, Chen-Hui Cao, Jin-Long Lin, Dan Xie, Feng-Wei Wang
Summary: The study reveals that TBX20 is downregulated in early-stage colorectal carcinoma (CRC) tissues and is associated with poor prognosis. TBX20 suppresses cell proliferation and tumor growth in CRC cells by inhibiting the non-homologous DNA end joining (NHEJ)-mediated repair. This research uncovers the tumor-suppressive role of TBX20 in CRC and provides a potential biomarker for predicting prognosis and a therapeutic target for combination therapy in early-stage CRC patients.
Article
Oncology
Xuan Li, Du Cai, Yaoyi Huang, Yumo Xie, Dingcheng Shen, Ze Yuan, Xiaoxia Liu, Meijin Huang, Yanxin Luo, Huichuan Yu, Xiaolin Wang
Summary: This study developed a DNA methylation biomarker to evaluate the prognosis of colorectal cancer (CRC) by identifying hypermethylated genes in cancer tissue from Illumina EPIC methylation arrays. The study found that RIMS2 was frequently hypermethylated and lowly expressed in CRC, and its methylation was associated with less frequent KRAS mutation and high differentiation. RIMS2 methylation showed independent predictive value for survival outcome and could predict prognosis better when combined with KRAS status.
Article
Developmental Biology
Peng-Fen Li, Yun-Gai Xiang, Dan Zhang, Na Lu, Qian Dou, Li Tan
Summary: The study revealed that LIG1 and LIG4 were downregulated in RPL patients, leading to increased DNA damages and cell apoptosis. SRSF1 and miR-383 were found to be involved in regulating the expression of LIG1 and LIG4, contributing to the pathophysiological processes of RPL.
Article
Biochemistry & Molecular Biology
Satu Maki-Nevala, Sanjeevi Ukwattage, Erkki-Ville Wirta, Maarit Ahtiainen, Ari Ristimaki, Toni T. Seppala, Anna Lepisto, Jukka-Pekka Mecklin, Paivi Peltomaki
Summary: Immunological and epigenetic changes play a role in tumorigenesis, with colitis-associated colorectal carcinomas (CA-CRC) and Lynch syndrome (LS) tumors showing differences in gene promoter methylation and immune cell distribution. CA-CRCs share a similar immune cell score and CD274 expression pattern with LS tumors, while increased methylation in normal mucosa may be a feature of CA-CRC-associated tumorigenesis.
Article
Hematology
Huiying Han, Gao Fan, Sha Song, Yunxin Jiang, Chen'ao Qian, Weimin Zhang, Qi Su, Xiaofeng Xue, Wenzhuo Zhuang, Bingzong Li
Summary: The study demonstrates that piRNA-30473 plays an oncogenic role in promoting the aggressive phenotype of DLBCL, and its depletion can reduce proliferation and induce cell cycle arrest. Through regulating m6A RNA methylation, the piRNA-30473/WTAP/HK2 axis contributes to the progression of DLBCL.
Article
Biochemistry & Molecular Biology
Chuan-Jian Shi, Shi-Ying Li, Chun-Hui Shen, Fei-Fei Pan, Li-Qiang Deng, Wei-Ming Fu, Ji-Yong Wang, Jin-Fang Zhang
Summary: In this study, it was found that Icariside II suppressed the proliferation of colorectal cancer (CRC) by inducing cell cycle arrest and apoptosis. It also inhibited tumor growth in vivo by suppressing the expression of beta-catenin and inactivating the Wnt/beta-catenin signaling pathway. Furthermore, Icariside II was shown to epigenetically target DNA methyltransferases (DNMTs) and decrease global DNA methylation levels, resulting in the suppression of circ beta-catenin biogenesis.
BIOORGANIC CHEMISTRY
(2022)
Article
Cardiac & Cardiovascular Systems
Congxia Bai, Ming Su, Yaohua Zhang, Yahui Lin, Yingying Sun, Li Song, Ning Xiao, Haochen Xu, Hongyan Wen, Meng Zhang, Jiedan Ping, Jing Liu, Rutai Hui, Hao Li, Jingzhou Chen
Summary: DNA methylation plays a crucial role in hypertension, with OVGP1 identified as a protein associated with hypertension that interacts with MYH9 to promote vascular remodeling and dysfunction.
Article
Cell Biology
Patricia Gonzalez-Rodriguez, Mathilde Cheray, Jens Fullgrabe, Maria Salli, Pinelopi Engskog-Vlachos, Lily Keane, Virginia Cunha, Agata Lupa, Wenbo Li, Qi Ma, Kristian Dreij, Michael G. Rosenfeld, Bertrand Joseph
Summary: Autophagy is a catabolic pathway that maintains cellular homeostasis and can be stimulated under cellular stress. The persistent downregulation of MAP1LC3 expression upon autophagy induction indicates an epigenetic memory of autophagy, offering insights into its long-term effects.
Review
Genetics & Heredity
Mohammed Ali Abbass, Brandie Leach, James Michael Church
Summary: The molecular basis of colorectal neoplasia is influenced by Mendelian genetics, with tumor suppressor genes playing a significant role in growth regulation compared to oncogenes. In patients with hereditary syndromes, the absence of one allele of a key tumor suppressor gene at birth can lead to tumorigenesis, triggered by the loss of expression of the second allele. There are multiple mechanisms through which the expression of the second allele of a tumor suppressor gene can be lost, impacting the phenotype.
Article
Oncology
Lina Fan, Chaochao Xu, Qiwei Ge, Yifeng Lin, Chi Chun Wong, Yadong Qi, Bin Ye, Qingwu Lian, Wei Zhuo, Jianmin Si, Shujie Chen, Liangjing Wang
Summary: The study identified a link between reduced abundance of A. muciniphila and colorectal cancer; supplementation with A. muciniphila suppressed colonic tumorigenesis; A. muciniphila induced M1-like macrophages may serve as a therapeutic target in the colorectal cancer tumor microenvironment.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Multidisciplinary Sciences
Ritwik Patra, Amit Kumar Dey, Suprabhat Mukherjee
Summary: Ulcerative colitis (UC) is a chronic inflammatory bowel disease that can lead to the development of colorectal carcinoma (CRC). This study explored the differential expression, functional enrichment, genomic alterations, signal transduction pathways, and immune infiltration levels of UC-critical genes in UC patients to understand their role in the oncogenesis of CRC. The study identified WFDC2, TTLL12, THRA, and EPHB3 as crucial genes involved in the molecular transformation of UC to CRC and suggested their potential as biomarkers and therapeutic targets for UC-induced human CRC.
Article
Biochemistry & Molecular Biology
William Martin, Gloria Sheynkman, Felice C. Lightstone, Ruth Nussinov, Feixiong Cheng
Summary: The rapid increase in computing power has greatly enhanced the capabilities of molecular dynamics simulations. Integrating learning techniques into analysis pipelines can reveal the kinetics of protein aggregation in Alzheimer's disease, but there are limitations and potential solutions.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Xiaoqin Pan, Xuan Lin, Dongsheng Cao, Xiangxiang Zeng, Philip S. Yu, Lifang He, Ruth Nussinov, Feixiong Cheng
Summary: This review introduces guidelines on utilizing deep learning methodologies and tools for drug repurposing, which is of great importance in drug development. The article summarizes the commonly used bioinformatics and pharmacogenomics databases for drug repurposing and discusses the recently developed sequence-based and graph-based representation approaches as well as state-of-the-art deep learning-based methods. The applications of drug repurposing in fighting the COVID-19 pandemic are presented, along with an outline of future challenges.
WILEY INTERDISCIPLINARY REVIEWS-COMPUTATIONAL MOLECULAR SCIENCE
(2022)
Article
Clinical Neurology
Jiansong Fang, Pengyue Zhang, Quan Wang, Chien-Wei Chiang, Yadi Zhou, Yuan Hou, Jielin Xu, Rui Chen, Bin Zhang, Stephen J. Lewis, James B. Leverenz, Andrew A. Pieper, Bingshan Li, Lang Li, Jeffrey Cummings, Feixiong Cheng
Summary: This study develops a network-based artificial intelligence framework that integrates multi-omics data with protein-protein interactome networks to accurately infer drug targets affected by GWAS-identified variants, leading to the discovery of new therapeutics. Through applying this approach to AD, 103 validated ARGs are identified, and three drugs are found to be significantly associated with decreased risk of AD.
ALZHEIMERS RESEARCH & THERAPY
(2022)
Article
Cardiac & Cardiovascular Systems
Muzna Hussain, Alison Krywanczyk, Eoin Donnellan, Trejeeve Martyn, Ossama Abou Hassan, Saqer Alkharabsheh, Chris Watson, W. H. Tang, Deborah Kwon, Paul Cremer, Feixiong Cheng, Mohamed Kanj, Brian Griffin, Carmela Tan, E. Rene Rodriguez, Mazen Hanna, Wael Jaber, Patrick Collier
Summary: The presence of atrial wall uptake (AU) on 99mTc-PyP scans is associated with an increased risk of atrial fibrillation (AF), independent of ATTR-CA diagnosis and sex. Overlooking AU on these scans may result in missing early disease manifestation or an additional predictor for the development of AF.
CIRCULATION-CARDIOVASCULAR IMAGING
(2022)
Editorial Material
Biochemistry & Molecular Biology
Feixiong Cheng, Nurcan Tuncbag
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Immunology
Grace E. Weber, Maria Khrestian, Elizabeth D. Tuason, Yvonne Shao, Jagan Pillai, Stephen Rao, Hao Feng, Yadi Zhou, Feixiong Cheng, Tara M. DeSilva, Shaun Stauffer, James B. Leverenz, Lynn M. Bekris
Summary: This study explores the relationship between human plasma sTREM2 and inflammatory activity in AD. The results suggest that there are different patterns of inflammatory activity across AD stages, indicating early-stage alterations in peripheral sTREM2-related inflammatory activity in AD. Three inflammatory factors exhibit lower levels in AD and a change in the relationship with sTREM2.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jennifer E. Dawson, Iris Nira Smith, William Martin, Krishnendu Khan, Feixiong Cheng, Charis Eng
Summary: PTEN, a chief regulator of cellular processes and a major tumor suppressor gene, remains elusive in terms of its structure and regulation of protein stability, post-translational modifications, and protein-protein interactions. In this study, multiple methods were employed to investigate the structure and molecular behavior of PTEN's PBD. The findings suggest that the PBD exists in multiple conformations, highlighting the importance of understanding how these specific conformational substates contribute to PTEN function, disease pathogenesis, and modulation of its tumor suppressor activity.
Editorial Material
Biochemistry & Molecular Biology
Feixiong Cheng, Daniel Geschwind
HUMAN MOLECULAR GENETICS
(2022)
Article
Clinical Neurology
Pengyue Zhang, Yuan Hou, Wanzhu Tu, Noll Campbell, Andrew A. Pieper, James B. Leverenz, Sujuan Gao, Jeffrey Cummings, Feixiong Cheng
Summary: The study found that moderate to high exposure to telmisartan was significantly associated with a reduced incidence of Alzheimer's disease in African Americans, but not in non-Hispanic European Americans. The medication possession ratio and average hypertension daily dosage of telmisartan were significantly associated with a stronger reduction in the incidence of both Alzheimer's disease and dementia in African Americans.
ALZHEIMERS & DEMENTIA
(2023)
Article
Biochemistry & Molecular Biology
William J. Massey, Venkateshwari Varadharajan, Rakhee Banerjee, Amanda L. Brown, Anthony J. Horak, Rachel C. Hohe, Bryan M. Jung, Yunguang Qiu, E. Ricky Chan, Calvin Pan, Renliang Zhang, Daniela S. Allende, Belinda Willard, Feixiong Cheng, Aldons J. Lusis, J. Mark Brown
Summary: We previously showed that knocking down Mboat7 in liver and adipose tissue led to high fat diet-induced hepatic steatosis, hyperinsulinemia, and systemic insulin resistance. Further studies demonstrated that hepatocyte-specific deletion of Mboat7 promoted fatty liver and NAFLD progression without affecting insulin sensitivity, indicating a potential cell autonomous role. Here, we found that Mboat7 function in adipocytes also contributes to diet-induced metabolic disturbances including hyperinsulinemia and systemic insulin resistance. Our findings suggest that Mboat7 plays a significant role in both liver and adipose tissue in regulating insulin resistance in mice.
JOURNAL OF LIPID RESEARCH
(2023)
Correction
Cell Biology
Jiansong Fang, Pengyue Zhang, Yadi Zhou, Chien-Wei Chiang, Juan Tan, Yuan Hou, Shaun Stauffer, Lang Li, Andrew A. A. Pieper, Jeffrey Cummings, Feixiong Cheng
Article
Clinical Neurology
A. Xavier Garcia, Jielin Xu, Feixiong Cheng, Eytan Ruppin, Alejandro A. Schaffer
Summary: This study re-analyzed three single-cell transcriptomics datasets and found that excitatory neurons have more differentially expressed genes in patients with Alzheimer's disease compared to unaffected controls. Synaptic transmission and related pathways are altered in a sex-specific analysis of excitatory neurons. X-chromosome genes and genes with heterogeneous X-inactivation status may contribute to the higher incidence of Alzheimer's disease in females.
ALZHEIMERS & DEMENTIA-TRANSLATIONAL RESEARCH & CLINICAL INTERVENTIONS
(2023)
Article
Biochemical Research Methods
Junlin Xu, Jielin Xu, Yajie Meng, Changcheng Lu, Lijun Cai, Xiangxiang Zeng, Ruth Nussinov, Feixiong Cheng
Summary: Single-cell RNA sequencing (scRNA-seq) is a revolutionary technology for determining gene expression at the individual cell level, but technical limitations result in heterogeneous and sparse data. In this study, a deep-learning approach called autoCell is presented for dropout imputation and feature extraction in scRNA-seq data. The effectiveness of autoCell is validated using simulated datasets and biologically relevant experiments. It provides a comprehensive toolbox for analyzing scRNA-seq data, including visualization, clustering, imputation, and disease-specific gene network identification.
CELL REPORTS METHODS
(2023)
