Article
Biochemistry & Molecular Biology
Yingwei Li, Zhongshao Chen, Jiali Peng, Cunzhong Yuan, Shi Yan, Ning Yang, Peng Li, Beihua Kong
Summary: This study found that SNRPB plays a key role in ovarian cancer and is associated with poor prognosis. Functionally, SNRPB knockdown inhibits ovarian cancer cell proliferation and invasion, while overexpression has the opposite effect. SNRPB expression increases after cisplatin treatment, and silencing SNRPB enhances ovarian cancer cell sensitivity to cisplatin. SNRPB promotes ovarian cancer progression by repressing exon 3 skipping of POLA1 and BRCA2.
Review
Oncology
Zhaoqi Liu, Raul Rabadan
Summary: This review summarizes the latest computational approaches to studying alternative splicing in cancer and highlights the current limitations of popular tools in this field. Additionally, some of the current computational challenges in characterizing the role of alternative splicing in cancer are discussed.
Article
Medicine, Research & Experimental
Martina Cusan, Haifeng Shen, Bo Zhang, Aijun Liao, Lu Yang, Meiling Jin, Mike Fernandez, Prajish Iyer, Yiming Wu, Kevyn Hart, Catherine Gutierrez, Sara Nik, Shondra M. Pruett-Miller, Jeremy Stark, Esther A. Obeng, Teresa Bowman, Catherine J. Wu, Ren-Jang Lin, Lili Wang
Summary: This research discovers that the mutation of RNA splicing factor SF3B1 results in the accumulation of centromeric R-loops, leading to increased chromosomal oscillation, impaired chromosome segregation, altered spindle architecture, and aneuploidy. The study reveals the relationship between dysregulated RNA splicing and chromosomal instability and highlights the role of centromeric R-loop augmentation in leukemogenesis.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Biotechnology & Applied Microbiology
Dong Cao
Summary: This study obtained neuronal circRNA data in C. elegans through large-scale neuron isolation and RNA sequencing, revealing that circRNAs are highly expressed in neurons and positively correlated with their cognate linear mRNAs. Deletion of reverse complementary match (RCM) sequences in circRNA flanking introns effectively abolished circRNA formation. RCMs not only promote back-splicing but also facilitate exon-skipping, providing a new explanation for the correlation between the two processes.
Article
Biochemistry & Molecular Biology
Miguel Barquin, Ian U. Kouzel, Beat Ehrmann, Michael Basler, Andreas J. Gruber
Summary: This study presents a single cell-based Terminal Exon Annotation database (scTEA-db), which provides yet unannotated terminal exons and associated transcript isoforms for studying their biological role in cell identity and function.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Asmaa Samy, Mehmet Kemal Ozdemir, Reda Alhajj
Summary: This study focuses on the relationship between SF3B1 and four types of cancer (MDS, AML, CLL, and BC). The results show that SF3B1 is more closely associated with hematologic malignancies (MDS, AML, CLL) than with breast cancer (BC). Different gene networks may be required to investigate the impact of mutant splicing factors on cancer development based on the type of cancer. Additionally, we summarized the set of genes and cellular pathways that are affected by aberrant splicing in cancerous cells based on the literature analyzed in this study.
SCIENTIFIC REPORTS
(2023)
Article
Biochemical Research Methods
Mengyuan Yang, Yiya Ke, Pora Kim, Xiaobo Zhou
Summary: Exon skipping is a common alternative splicing event that can contribute to human diseases. ExonSkipAD database provides functional annotation of ES events in AD and identifies potential therapeutic targets.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Cardiac & Cardiovascular Systems
Jia Li, Kaiying Wang, Yuchen Zhang, Tuan Qi, Juanjuan Yuan, Lei Zhang, Han Qiu, Jinxi Wang, Huang-Tian Yang, Yi Dai, Yan Song, Xing Chang
Summary: The study analyzed a novel murine model of DMD and examined the feasibility of using a cytidine base editor for exon skipping in vivo. The results showed that AAV9-eTAM treatment in the mouse model restored dystrophin and improved cardiac and skeletal muscle functions significantly.
Article
Multidisciplinary Sciences
Young Jin Kim, Nicole Sivetz, Jessica Layne, Dillon M. Voss, Lucia Yang, Qian Zhang, Adrian R. Krainer
Summary: Mutations in the CFTR gene cause cystic fibrosis (CF), and the CFTR-W1282X mutation results in severe CF. Current therapies for CF benefit most patients, but targeted therapy for patients with the W1282X mutation is lacking. This study explores a potential solution by using an exon-skipping antisense oligonucleotide strategy to bypass nonsense-mediated mRNA decay (NMD) and increase the expression of CFTR protein. The results pave the way for developing allele-specific therapy for CF caused by the W1282X mutation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Medicine, Research & Experimental
Melita Kaltak, Rocio Blanco-Garavito, Laurie L. Molday, Claire-Marie Dhaenens, Eric E. Souied, Gerard Platenburg, Jim Swildens, Robert S. Molday, Frans P. M. Cremers
Summary: This study investigated the exon skipping phenomenon of exon 17 in the ABCA4 gene associated with Stargardt disease (STGD1) and designed corresponding oligonucleotides to induce exon 17 skipping. The results showed that the deletion of exon 17 in ABCA4 does not result in the absence of protein activity and does not cause a severe STGD1 phenotype when in trans with a null allele. Therefore, the impact of severe variants in exon 17 can potentially be ameliorated by exon skipping using antisense oligonucleotides (AONs), generating partial ABCA4 activity in STGD1 patients.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Agronomy
Lei Liu, Depeng Wu, Yujuan Gu, Fuxia Liu, Bin Liu, Feng Mao, Xin Yi, Tang Tang, Xiangxiang Zhao
Summary: The study found that alternative splicing changes can lead to an increase in transcriptomic diversity during secondary dormancy induction, with intron retention being the dominant splicing type. The global isoform expression percentage variations in alternative splicing are more significant in differentially expressed genes (DEGs) than in non-DEGs. Spliceosome components are overrepresented among the differently spliced genes associated with secondary dormancy.
MOLECULAR BREEDING
(2022)
Article
Agriculture, Dairy & Animal Science
Qingyuan Ouyang, Shenqiang Hu, Qingliang Chen, Shuai Xin, Zhiyu He, Jiwei Hu, Bo Hu, Hua He, Hehe Liu, Liang Li, Jiwen Wang
Summary: This study identifies molecular markers and mechanisms related to egg production in geese, specifically highlighting the role of the ATP1A1 gene in follicle selection and maturation processes.
Article
Multidisciplinary Sciences
Ysobel R. Baker, Cameron Thorpe, Jinfeng Chen, Laura M. Poller, Lina Cox, Pawan Kumar, Wooi F. Lim, Lillian Lie, Graham McClorey, Sven Epple, Daniel Singleton, Michael A. McDonough, Jack S. Hardwick, Kirsten E. Christensen, Matthew J. A. Wood, James P. Hall, Afaf H. El-Sagheer, Tom Brown
Summary: This study describes reduced-charge oligonucleotides containing artificial LNA-amide linkages, which have improved bioavailability and therapeutic efficacy, making it a potential new approach for treating untreatable diseases.
NATURE COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Franciscus C. Vermeer, Jeroen Bremer, Robert J. Sietsma, Aileen Sandilands, Robyn P. Hickerson, Marieke C. Bolling, Anna M. G. Pasmooij, Henny H. Lemmink, Morris A. Swertz, Nine V. A. M. Knoers, K. Joeri van der Velde, Peter C. van den Akker
Summary: Epidermolysis bullosa is a genetic skin condition characterized by skin fragility caused by gene variants, with treatment currently focused on symptom relief. Exon skipping shows potential as a therapeutic strategy for EB, with the severity of the disease linked to gene involvement and variants.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Bo Zhao, Xin Hu, Yuning Zhou, Yueru Shi, Rui Qian, Youzhong Wan
Summary: SF3B1, an essential component of the U2 snRNP, is frequently mutated in cancers, leading to aberrant RNA splicing at 3' splice sites. Mutated SF3B1 prefers alternative branchpoint sequences with higher affinity to U2 snRNA for splicing, affecting the splicing of DVL2. The selection of branchpoint sequences for splicing is influenced by the affinity to U2 snRNA and the distance to the 3'ss.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Genetics & Heredity
Melissa Nel, Amokelani C. Mahungu, Nomakhosazana Monnakgotla, Gerrit R. Botha, Nicola J. Mulder, Gang Wu, Evadnie Rampersaud, Marka van Blitterswijk, Joanne Wuu, Anne Cooley, Jason Myers, Rosa Rademakers, J. Paul Taylor, Michael Benatar, Jeannine M. Heckmann
Summary: This study performed a screening of 44 ALS genes in ALS patients with African genetic ancestry using whole-genome sequencing data and identified pathogenic variants in 13% of the cases, with C9orf72 and SOD1 being the most common genes.
NEUROLOGY-GENETICS
(2022)
Article
Oncology
Wenqing Qi, Wojciech Rosikiewicz, Zhaohong Yin, Beisi Xu, Huihong Jiang, Shibiao Wan, Yiping Fan, Gang Wu, Lu Wang
Summary: Mesenchymal chondrosarcoma is a rare and aggressive primitive mesenchymal tumor that mainly affects adolescents and young adults. Researchers have identified the fusion protein HEY1-NCOA2, which promotes cell proliferation and upregulates the expression of PDGFB and PDGFRA, providing a potential target for treating mesenchymal chondrosarcoma.
JOURNAL OF PATHOLOGY
(2022)
Article
Multidisciplinary Sciences
Wenan Chen, Shuoguo Wang, Saima Sultana Tithi, David W. Ellison, Daniel J. Schaid, Gang Wu
Summary: This article introduces a framework that can control confounding factors in clinical and cancer genomics studies to identify genes enriched with pathogenic variants. By controlling genotype summary counts from public data sets, this framework provides a cost-effective solution for prioritizing disease-risk genes enriched with rare pathogenic variants.
NATURE COMMUNICATIONS
(2022)
Article
Hematology
Jamie E. Flerlage, Jason R. Myers, Jamie L. Maciaszek, Ninad Oak, Sara R. Rashkin, Yawei Hui, Yong-Dong Wang, Wenan Chen, Gang Wu, Ti-Cheng Chang, Kayla Hamilton, Saima S. Tithi, Lynn R. Goldin, Melissa Rotunno, Neil Caporaso, Aurelie Vogt, Deborah Flamish, Kathleen Wyatt, Jia Liu, Margaret Tucker, Christopher N. Hahn, Anna L. Brown, Hamish S. Scott, Charles Mullighan, Kim E. Nichols, Monika L. Metzger, Mary L. McMaster, Jun J. Yang, Evadnie Rampersaud
Summary: Familial aggregation of HL has been shown to have a genetic component. In this study, whole genome sequencing was performed on individuals with and without HL from pedigrees with multiple affected relatives. A total of 44 HL-risk variants were identified, including both coding and noncoding variants. The study also identified several novel variants and observed segregation patterns in most pedigrees.
Article
Oncology
Chih-Hsiang Yu, Shiann-Tarng Jou, Ying-Hui Su, Elane Coustan-Smith, Gang Wu, Chao-Neng Cheng, Meng-Yao Lu, Kai-Hsin Lin, Kang-Hsi Wu, Shu-Huey Chen, Fang-Liang Huang, Hsiu-Hao Chang, Jinn-Li Wang, Hsiu-Ju Yen, Meng-Ju Li, Shu-Wei Chou, Wan-Ling Ho, Yen-Lin Liu, Chia-Ching Chang, Ze-Shiang Lin, Chien-Yu Lin, Hsuan-Yu Chen, Yu-Ling Ni, Dong-Tsamn Lin, Shu-Wha Lin, Jun J. Yang, Yen-Hsuan Ni, Ching-Hon Pui, Sung-Liang Yu, Yung-Li Yang
Summary: This study analyzed data from two consecutive protocols to determine the clinical impact of minimal/measurable residual disease (MRD) and tumor genetic subtypes in newly diagnosed pediatric acute lymphoblastic leukemia (ALL) patients. The results showed that MRD-directed therapy improved outcomes for pediatric ALL, especially for standard-risk patients. This study provides important data to inform the design of future clinical trials in Taiwan.
Article
Oncology
Jennifer L. Kamens, Jinjun Dang, Timothy I. Shaw, Alexander M. Gout, Scott Newman, Kohei Hagiwara, Amelia M. R. Smith, Alyssa N. Obermayer, Sarah Aldridge, Jing Ma, Yang Zhang, Gang Wu, Vasiliki Leventaki, Teresa Santiago, Susana Raimondi, Joy Nakitandwe, Alberto Pappo, Chunliang Li, Jinghui Zhang, Tanja A. Gruber
Summary: This study reports a case of myeloid sarcoma with fusion oncogene CIC-NUTM2A, suggesting its clonal evolution from bone marrow despite the absence of pathology. Murine modeling confirmed the transforming ability of the fusion gene and identified RTK signaling activation. These findings broaden the definition of CIC-rearranged malignancies and emphasize the importance of molecular analysis and tracking bone marrow involvement in myeloid sarcoma.
MOLECULAR CANCER RESEARCH
(2023)
Letter
Hematology
Carolin Escherich, Wenan Chen, Satoshi Miyamoto, Yui Namikawa, Wenjian Yang, David T. Teachey, Zhenhua Li, Elizabeth A. Raetz, Eric Larsen, Meenakshi Devidas, Paul L. Martin, Gang Wu, Ching-Hon Pui, Stephen P. Hunger, Mignon L. Loh, Masatoshi Takagi, Jun J. Yang
Article
Hematology
Qingsong Gao, Sarra L. Ryan, Ilaria Iacobucci, Pankaj S. Ghate, Ruth E. Cranston, Claire Schwab, Abdelrahman H. Elsayed, Lei Shi, Stanley Pounds, Shaohua Lei, Pradyuamna Baviskar, Deqing Pei, Cheng Cheng, Matthew Bashton, Paul Sinclair, David R. Bentley, Mark T. Ross, Zoya Kingsbury, Terena James, Kathryn G. Roberts, Meenakshi Devidas, Yiping Fan, Wenan Chen, Ti-Cheng Chang, Gang Wu, Andrew Carroll, Nyla Heerema, Virginia Valentine, Marcus Valentine, Wenjian Yang, Jun J. Yang, Anthony Moorman, Christine J. Harrison, Charles G. Mullighan
Summary: In this study, the genomic and transcriptomic profiles of 124 patients with iAMP21-ALL were analyzed, revealing subgroups based on copy number alteration and structural variation. The study identified a common amplification region on chromosome 21 and found several differentially expressed genes associated with acute leukemia. Single-cell genomic profiling showed clonal heterogeneity and genomic evolution, indicating that the acquisition of iAMP21 is an early event that may progress during disease development. The study also found characteristic secondary genetic features and suggested the use of cytogenetic or genomic methods for precise diagnosis of iAMP21-ALL.
Article
Hematology
Zhenhua Li, Ti-Cheng Chang, Jacob J. Junco, Meenakshi Devidas, Yizhen Li, Wenjian Yang, Xin Huang, Dale J. Hedges, Zhongshan Cheng, Mary Shago, Andrew J. Carroll, Nyla A. Heerema, Julie Gastier-Foster, Brent L. Wood, Michael J. Borowitz, Lauren Sanclemente, Elizabeth A. Raetz, Stephen P. Hunger, Eleanor Feingold, Tracie C. Rosser, Stephanie L. Sherman, Mignon L. Loh, Charles G. Mullighan, Jiyang Yu, Gang Wu, Philip J. Lupo, Karen R. Rabin, Jun J. Yang
Summary: This study investigates the genomics of Down syndrome-related acute lymphoblastic leukemia (DS-ALL) and identifies 15 molecular subtypes, as well as abnormal activation of key genes. It also reveals the common occurrence of somatic genomic abnormalities mediated by gene rearrangements in DS-ALL and the association between subtype heterogeneity and prognosis. These findings provide important insights into the biology of DS-ALL and offer opportunities for individualized treatment.
Article
Oncology
Jia Xie, Teneema Kuriakose, Brandon Bianski, Nathaniel Twarog, Evan Savage, Ke Xu, Xiaoyan Zhu, Chen He, Baranda Hansen, Hong Wang, Anthony High, Yuxin Li, Jerold E. Rehg, Heather S. Tillman, Burgess B. Freeman, Zoran Rankovic, Arzu Onar-Thomas, Yiping Fan, Gang Wu, Junmin Peng, Shondra Miller, Suzanne J. Baker, Anang A. Shelat, Christopher L. Tinkle
Summary: This study aimed to evaluate the therapeutic potential and molecular consequences of combining radiation with selective DDR inhibition in pediatric high-grade glioma (pHGG). The results showed that the ATM inhibitor AZD1390 significantly potentiated radiation in pHGG, regardless of TP53 status. Additionally, a novel mechanism of resistance to AZD1390 + radiation was identified, which involved attenuated ATM pathway response and synthetic lethality with ATR inhibition.
Article
Multidisciplinary Sciences
Yanling Liu, Jonathon Klein, Richa Bajpai, Li Dong, Quang Tran, Pandurang Kolekar, Jenny L. Smith, Rhonda E. Ries, Benjamin J. Huang, Yi-Cheng Wang, Todd A. Alonzo, Liqing Tian, Heather L. Mulder, Timothy I. Shaw, Jing Ma, Michael P. Walsh, Guangchun Song, Tamara Westover, Robert J. Autry, Alexander M. Gout, David A. Wheeler, Shibiao Wan, Gang Wu, Jun J. Yang, William E. Evans, Mignon Loh, John Easton, Jinghui Zhang, Jeffery M. Klco, Soheil Meshinchi, Patrick A. Brown, Shondra M. Pruett-Miller, Xiaotu Ma
Summary: The authors identified 272 oncogenic fusions in childhood cancer patients and explored their etiologies, links with tumor progression, and therapeutic potential. These findings have important clinical implications, such as risk stratification and genome-editing-based therapeutics.
NATURE COMMUNICATIONS
(2023)
Article
Clinical Neurology
Caroline A. McHutchison, Joanne Wuu, Corey T. McMillan, Rosa Rademakers, Jeffrey Statland, Gang Wu, Evadnie Rampersaud, Jason Myers, Jessica P. Hernandez, Sharon Abrahams, Michael Benatar, CReATe Consortium
Summary: In this study, researchers explored the cognitive and behavioral changes in people with motor neuron disease (MND) over time. They found that cognitive impairment was less common than previously reported and remained stable for most participants. However, a small subset of participants experienced a decline in cognition over time, which was not solely related to the C9ORF72 genetic mutation. These findings raise questions about the timing and progression of cognitive impairment in MND.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Article
Multidisciplinary Sciences
Yurika Matsui, Mohamed Nadhir Djekidel, Katherine Lindsay, Parimal Samir, Nina Connolly, Gang Wu, Xiaoyang Yang, Yiping Fan, Beisi Xu, Jamy C. Peng
Summary: The study shows that SNIP1 is critical for the survival and differentiation of stem cells in the developing brain. It regulates PRC2 activities downstream of TGFb and NFkB, influencing cell fates. Understanding the role of SNIP1 in brain development can provide insights into cell survival and death during development.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
George Daniel Grass, Dalia Ercan, Alyssa N. Obermayer, Timothy Shaw, Paul A. Stewart, Jad Chahoud, Jasreman Dhillon, Alex Lopez, Peter A. S. Johnstone, Silvia Regina Rogatto, Philippe E. Spiess, Steven A. Eschrich
Summary: This study provides the first description of the surfaceome in penile cancer and evaluates the impact of human papillomavirus (HPV) infection on surfaceome diversity. The analysis found a diverse surfaceome within patient tumors, with a high proportion of membrane proteins and transporters. The study also identified significant differences in protein classes based on HPV status and a prognostic immunoglobulin protein called BSG/CD147.
Article
Oncology
Cheng Chen, Na Qin, Mingjuan Wang, Qian Dong, Saima Sultana Tithi, Yawei Hui, Wenan Chen, Gang Wu, Dennis Kennetz, Michael N. Edmonson, Michael C. Rusch, Andrew Thrasher, John Easton, Heather L. Mulder, Nan Song, Noel -Marie Plonski, Kyla Shelton, Cindy Im, Matthew J. Ehrhardt, Kim E. Nichols, Wendy M. Leisenring, Kayla L. Stratton, Rebecca Howell, Yutaka Yasui, Smita Bhatia, Gregory Armstrong, Kirsten K. Ness, Melissa M. Hudson, Jinghui Zhang, Hui Wang, Deo Kumar Srivastava, Leslie L. Robison, Zhaoming Wang
Summary: Carriers of cancer predisposing variants are at an increased risk of developing subsequent malignant neoplasms among childhood cancer survivors. Implementing early personalized cancer surveillance and prevention strategies based on genetic counseling and clinical genetic testing can reduce the risk of subsequent malignant neoplasm-related mortality.