Article
Biochemistry & Molecular Biology
Shani Journo, Anat Klein Goldberg, Ethan S. Sokol, Lotem Zinger, Metsada Pasmanik-Chor, Boris Sarvin, Dor Simkin, Sivan Fuchs, Tomer Shlomi, Ido Wolf, Tami Rubinek
Summary: This study aimed to investigate the genomic alterations (GA) that mediate the tropism and metastasis formation of pancreatic ductal adenocarcinoma (PDAC) cells to the liver. It was found that the deletion of CDKN2A/B played a significant role in promoting liver metastasis by enhancing the tumorigenic phenotype of PDAC cells. Additionally, these cells showed unique adaptations to the high-ammonia low-glutamine environment in the liver, including regulation of genes involved in glutaminolysis. These findings provide insights into the vulnerabilities of PDAC cells and may contribute to the development of novel therapeutic strategies for preventing liver metastasis formation.
Article
Oncology
Jenna K. Minami, Danielle Morrow, Nicholas A. Bayley, Elizabeth G. Fernandez, Jennifer J. Salinas, Christopher Tse, Henan Zhu, Baolong Su, Rhea Plawat, Anthony Jones, Alessandro Sammarco, Linda M. Liau, Thomas G. Graeber, Kevin J. Williams, Timothy F. Cloughesy, Scott J. Dixon, Steven J. Bensinger, David A. Nathanson
Summary: Malignant tumors exhibit heterogeneous metabolic reprogramming, hindering the identification of vulnerabilities for metabolism-targeted therapy. Through analysis of lipidomic, transcriptomic, and genomic data, this study identifies CDKN2A deletion as a molecular alteration that remodels the lipidome in glioblastoma (GBM), leading to higher lipid peroxidation and selective vulnerability to ferroptosis. This research provides a resource for understanding the molecular and lipidomic characteristics of GBM, and reveals a potential therapeutic target related to altered lipid metabolism.
Article
Oncology
Juanli Qiao, Yuan Tian, Xiaojing Cheng, Zhaojun Liu, Jing Zhou, Liankun Gu, Baozhen Zhang, Lianhai Zhang, Jiafu Ji, Rui Xing, Dajun Deng
Summary: The study suggests that somatic copy number deletion of the CDKN2A gene may drive gastric cancer metastasis and could serve as a predictor for hematogenous metastasis of gastric cancers.
FRONTIERS IN ONCOLOGY
(2021)
Article
Endocrinology & Metabolism
Christian H. Burns, Belinda Yau, Anjelica Rodriguez, Jenna Triplett, Drew Maslar, You Sun An, Reini E. N. van der Welle, Ross G. Kossina, Max R. Fisher, Gregory W. Strout, Peter O. Bayguinov, Tineke Veenendaal, David Chitayat, James A. J. Fitzpatrick, Judith Klumperman, Melkam A. Kebede, Cedric S. Asensio
Summary: VPS41 is essential for insulin granule biogenesis and regulated insulin secretion. Loss of VPS41 results in reduced insulin granule number, changes in transmembrane protein composition, and defects in granule-regulated exocytosis, ultimately leading to diabetes in mice.
Article
Gastroenterology & Hepatology
Xintong Jia, Bin Sun, Qiu Tu, Huaxin Qi, Lin Li, Xiuyun Liu, Lanzhen Yan, Hongjuan Dai, Qingpeng Kong, Chengwei Tang, Xudong Zhao
Summary: The study revealed the essential role of Smad4 deficiency in pancreatic ductal adenocarcinoma (PDAC) formation. This model better recapitulates the adult onset, clonal origin, and genetic alterations in human PDAC and can be simply generated on a large scale.
Review
Oncology
Marion Grard, Camille Chatelain, Tiphaine Delaunay, Elvire Pons-Tostivint, Jaafar Bennouna, Jean-Francois Fonteneau
Summary: The review discusses the potential impact of homozygous deletion of IFN I genes on thoracic cancers therapy, advocating for better consideration of this genetic alteration in patient monitoring.
FRONTIERS IN ONCOLOGY
(2021)
Article
Clinical Neurology
Xiaopeng Cui, Wen-Qiang Xin, Bangyue Wang, Yan Zhao, Changkai Hou, Shifei Cai, Chao Peng, Zhen Wang, Jian Li, Linchun Huan, Lei Chen, Xinyu Yang
Summary: The study examined the association between SNPs of the CDKN2A/CDKN2B gene on chromosome 9p21.3 and intracranial aneurysm (IA) risk in the Chinese Han population. The results showed that rs10811661 and rs4977574 were significantly associated with IA, highlighting the need for further investigation.
NEUROPSYCHIATRIC DISEASE AND TREATMENT
(2021)
Letter
Dermatology
Samantha L. Wong, Daniela Martiniuc, Maija Kiuru
Summary: This article describes a family with a deletion of exon 1B in CDKN2A, who had multiple cutaneous melanomas, neural tumors, and various malignancies.
CLINICAL AND EXPERIMENTAL DERMATOLOGY
(2022)
Article
Toxicology
Diana M. Paredes-Cespedes, Yael Yvette Bernal-Hernandez, Jose Francisco Herrera-Moreno, Aurora Elizabeth Rojas-Garcia, Irma Martha Medina-Diaz, Cyndia A. Gonzalez-Arias, Briscia Socorro Barron-Vivanco
Summary: This study aimed to investigate the methylation profiles of the CDKN2B and CDKN2A genes in a genetically conserved population exposed to pesticides. The results showed that the farmer group had a higher methylation percentage of CDKN2B than the non-farmer group, while no differences in CDKN2A were observed between groups. These results suggest that pesticide exposure and exposure time could modify the methylation pattern of the CDKN2B gene in Huichol indigenous individuals.
HUMAN & EXPERIMENTAL TOXICOLOGY
(2022)
Article
Oncology
Jessica Merkle, Markus Breunig, Maximilian Schmid, Chantal Allgoewer, Jana Krueger, Michael K. Melzer, Susanne Bens, Reiner Siebert, Lukas Perkhofer, Ninel Azoitei, Thomas Seufferlein, Sandra Heller, Matthias Meier, Martin Mueller, Alexander Kleger, Meike Hohwieler
Summary: The study provides a hereditary human pancreatic cancer model using patient-specific CDKN2A-mutated pluripotent stem cells to investigate tumor initiation and early development, revealing structural and molecular changes following inducible KRAS(G12D) expression in pancreatic duct-like organoids (PDLOs).
Article
Clinical Neurology
Raquel T. Yokoda, William S. Cobb, Raymund L. Yong, John F. Crary, Mariano S. Viapiano, Jamie M. Walker, Melissa Umphlett, Nadejda M. Tsankova, Timothy E. Richardson
Summary: Homozygous deletion of CDKN2A/B is considered a molecular signature for grade 4 in IDH-mutant astrocytomas, but there are no grading recommendations for lower-grade IDH-mutant astrocytomas with CDKN2A mutation or other alterations. We evaluated a cohort of IDH-mutant astrocytomas and found that those with CDKN2A mutation had worse survival outcomes, similar to those with CDKN2A deletion. These findings suggest that CDKN2A mutation should be considered for grading schemes.
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2023)
Review
Gastroenterology & Hepatology
Hirokazu Kimura, Alison P. Klein, Ralph H. Hruban, Nicholas J. Roberts
Summary: CDKN2A plays a crucial role in the development of pancreatic cancer, with carriers of pathogenic germline variants having an increased risk of the disease.
Article
Oncology
Sofian Al Shboul, Shelagh Boyle, Ashita Singh, Tareq Saleh, Moath Alrjoub, Ola Abu Al Karsaneh, Amel Mryyian, Rand Dawoud, Sinem Gul, Shaden Abu Baker, Kathryn Ball, Ted Hupp, Paul M. Brennan
Summary: Deletion of CDKN2A and IFNA14 genes on chromosome 9 in glioblastomas may occur simultaneously, and their co-deletion is negatively correlated with patient survival. The intact status of CDKN2A/IFNA14 is associated with longer survival and second surgery, indicating improved patient outcomes.
BRAIN TUMOR PATHOLOGY
(2023)
Article
Cell Biology
Yan Wang, Sheng Zhang, Zhaohui Lan, Vui Doan, Bokyung Kim, Sihan Liu, Meina Zhu, Vanessa L. Hull, Sami Rihani, Chun-Li Zhang, John A. Gray, Fuzheng Guo
Summary: Children with SOX2 deficiency may develop ocular disorders and extra-ocular CNS anomalies. Within the central nervous system, SOX2 deficiency in astroglial cells can lead to abnormal brain development, resulting in hyperactivity in locomotion and increased neuronal excitability. This deficiency inhibits postnatal astrocyte maturation without affecting proliferation, affecting molecular, morphological, and electrophysiological aspects.
Article
Oncology
Motaz Ashkar, Shruti Chandra, Santhi Swaroop Vege, Hiroaki Takahashi, Naoki Takahashi, Robert R. McWilliams
Summary: In patients receiving ICI therapy, the majority of pancreatic irAEs were classified as asymptomatic pancreatic injury with some risk of pancreatic atrophy. This classification can help in assessing patterns of pancreatic involvement, pathogenesis, and treatment decisions.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Letter
Cell Biology
Dongming Xu, Cuiping Yang, Qiushuo Shen, Shengkai Pan, Zhen Liu, Tongzuo Zhang, Xin Zhou, Menglong Lei, Peng Chen, Hui Yang, Tao Zhang, Yuanting Guo, Xiangjiang Zhan, Yongbin Chen, Peng Shi
Article
Biochemistry & Molecular Biology
Zhen Liu, Peng Chen, Yuan-Yuan Li, Meng-Wen Li, Qi Liu, Wen-Lu Pan, Dong-Ming Xu, Jing Bai, Li-Biao Zhang, Jie Tang, Peng Shi
Summary: The cochlear hair cells of echolocating bats show resistance to intense noise, preventing noise-induced hearing loss. Experimental evidence indicates that echolocating bats can maintain their hearing and cochlear health even after exposure to continuous intense noise.
JOURNAL OF GENETICS AND GENOMICS
(2021)
Letter
Biochemistry & Molecular Biology
Hui Yang, Songlin Yang, Fei Fan, Yun Li, Shaoxing Dai, Xin Zhou, Cynthia C. Steiner, Bretton Coppedge, Christian Roos, Xianghai Cai, David M. Irwin, Peng Shi
Summary: Research has shown that the family size variance of bitter taste receptors genes correlates with dietary preference in animals; however, there have been few systematic studies on the functional evolution of specific Tas2R. A parallel amino acid substitution in Tas2R16 shared by humans and white-faced sakis was found, leading to increased sensitivity to beta-glucopyranosides in both species.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Article
Biochemistry & Molecular Biology
Tao Zhang, Jie Chen, Jia Zhang, Yuan-Ting Guo, Xin Zhou, Meng-Wen Li, Zhi-Zhong Zheng, Tong-Zuo Zhang, Robert W. Murphy, Eviatar Nevo, Peng Shi
Summary: This study analyzed the phenotypic and genomic data of plateau zokor populations at different elevations, revealing potential differences in adaptation mechanisms among populations living in extreme high elevation environments. The populations living at the highest elevations showed specific adaptations in cardiovascular and erythrocyte traits, possibly driven by positive selection. Overall, heterogeneous stressors impact adaptations to extreme elevations, highlighting stress-dependent and genetically constrained adaptation to hypoxia.
Article
Biology
Zhizhong Zheng, Rong Hua, Guoqiang Xu, Hui Yang, Peng Shi
Summary: This study provides new insights into the molecular basis of subterranean adaptations and highlights the importance of gene losses in mammalian evolution.
Article
Microbiology
Zhanshan (Sam) Ma, Wendy Li, Peng Shi
Summary: Based on a meta-analysis of a large dataset, this study reveals the relationship between animal gastrointestinal microbiome diversity and host phylogeny and diet, suggesting that power-law patterns govern this relationship.
FEMS MICROBIOLOGY ECOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Junjun Hao, Wuling Hao, Zhen Liu, Peng Shi
Summary: The prenatal-to-postnatal transition is a crucial process in an organism's life cycle, involving physiological adaptations to extrauterine stresses. However, the molecular basis of these adaptations remains unclear. In this study, we analyzed the transcriptomes of seven organs from five mammalian species and identified a developmental shift in gene expression during the perinatal stage. The genes with low-to-high and high-to-low expression during this stage were found to be involved in various physiological adaptations, such as lipid metabolism, circadian rhythm, immune response, cell cycle, and cell division. These genes also formed mutually inhibitory toggle switch pairs, highlighting the importance of gene regulatory networks in the prenatal-to-postnatal transition. We propose a toggle switch model to investigate the mechanisms underlying the developmental shift in gene expression and the physiological adaptations during this transition.
MOLECULAR BIOLOGY AND EVOLUTION
(2022)
Article
Neurosciences
Peng Chen, Jun-Jun Hao, Meng-Wen Li, Jing Bai, Yuan-Ting Guo, Zhen Liu, Peng Shi
Summary: This study constructed gene co-expression networks and found shared molecular mechanisms, including apoptosis, immune response, inflammation, and ion transport, across different types of SNHL. Several potential hub regulators, such as IL1B and CCL2, were identified and shown to play a crucial role in promoting apoptosis. These findings provide insights into potential therapeutic targets for SNHL.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Genetics & Heredity
Jimei Li, Zhifang An, Linna Wei, Bo Xu, Zhijie Wang, Conghui Gao, Lian Wei, Delin Qi, Peng Shi, Tongzuo Zhang, Dengbang Wei
Summary: This study identified a novel heme-containing protein, named gamma(4)-like, in the pulmonary surfactant of plateau zokors. The protein has a higher affinity to oxygen and increases the oxygen-dissolving capability, which benefits the zokors in obtaining oxygen in the low-oxygen environment.
FRONTIERS IN GENETICS
(2022)
Article
Multidisciplinary Sciences
Zhen Liu, Peng Chen, Dong-Ming Xu, Fei-Yan Qi, Yuan-Ting Guo, Qi Liu, Jing Bai, Xin Zhou, Peng Shi
Summary: Research finds that the laryngeal echolocation in bats may have originated from a common ancestor, but is lost in some fruit bats.
Article
Oncology
Qiu Tu, Xiuyun Liu, Xiaoqing Yao, Ruixue Li, Gaojing Liu, Honglv Jiang, Kaiqin Li, Qiongfang Chen, Xiaoyan Huang, Qing Chang, Guoqiang Xu, Hong Zhu, Peng Shi, Bo Zhao
Summary: This study identified RETSAT as a novel replication fork protein in pancreatic ductal adenocarcinoma (PDAC) cells. RETSAT functions by interacting with DDX39B to promote fork restarting and increase cellular resistance to replication stresses co-induced by tumor environmental hypoxia and gemcitabine.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Cell Biology
Zhifang An, Linna Wei, Bo Xu, Zhijie Wang, Conghui Gao, Jimei Li, Lian Wei, Delin Qi, Peng Shi, Tongzuo Zhang, Dengbang Wei
Summary: This study investigates the expression of the protein HBD in the lungs of plateau pikas and finds that when HBD expression is downregulated, the pikas show hypoxemia. These findings provide insights into the adaptive mechanisms of plateau pikas in high-altitude environments.
Article
Multidisciplinary Sciences
Qi Long, Kai Yan, Chendong Wang, Yanling Wen, Furong Qi, Hui Wang, Peng Shi, Xingguo Liu, Wai-Yee Chan, Xuemei Lu, Hui Zhao
Summary: Increasing evidence shows that interspecific hybridization plays a crucial role in speciation, but chromatin compatibility issues often hinder this process. Genomic imbalances, such as chromosomal DNA loss and rearrangements, lead to infertility in hybrids. The mechanism behind reproductive isolation in interspecific hybridization remains unknown. In this study, it was found that the modification of maternally defined H3K4me3 in Xenopus laevis and Xenopus tropicalis hybrids determines the fate of the hybrids, with texls showing developmental arrest and lexts being viable. Transcriptomic analysis revealed that the P53 pathway is overactivated and the Wnt signaling pathway is suppressed in texls hybrids. Furthermore, the lack of maternal H3K4me3 disrupts gene expression balance between the L and S subgenomes in texls hybrids. Attenuation of p53 can delay the arrested development of texls. This study proposes an additional model of reproductive isolation based on modifications of maternally defined H3K4me3.
Article
Cell Biology
Dong Yang, Bin Sun, Shirong Li, Wenwen Wei, Xiuyun Liu, Xiaoyue Cui, Xianning Zhang, Nan Liu, Lanzhen Yan, Yibin Deng, Xudong Zhao
Summary: Cellular senescence plays an important role in aging and age-associated pathologies. NKG2DLs are up-regulated in senescent cells, and CAR T cells targeting NKG2DLs can effectively diminish senescent cells, improving age-associated pathologies and physical performance.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Zoology
Tao Zhang, Meng-Long Lei, Hao Zhou, Zhong-Zheng Chen, Peng Shi
Summary: In this study, the taxonomic and phylogenetic relationships of Eospalax, a genus of subterranean rodents endemic to China, were investigated using genomic and morphological analyses. The study identified six previously described species and discovered a new species, Eospalax muliensis sp. nov., which diverged from closely related species shortly after the first divergence in the genus. The findings contribute to our understanding of the evolution and taxonomy of Eospalax.
ZOOLOGICAL RESEARCH
(2022)
