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.
Review
Cell Biology
Ning Wang, Yue Hu, Zefeng Wang
Summary: Eukaryotic gene expression is tightly regulated at multiple levels, including alternative splicing, which generates multiple mRNA isoforms from a single gene. Epigenetic modifications play crucial roles in the regulation of alternative splicing by affecting transcription, splicing factor recruitment, and splicing factor expression/activity. Dysregulation of epigenetics and splicing is common in cancer and can have functional consequences. Understanding the complex regulation of gene expression layers can provide new insights into modulating disease-related splicing dysregulation.
WILEY INTERDISCIPLINARY REVIEWS-RNA
(2023)
Article
Plant Sciences
Ibtissam Jabre, Saurabh Chaudhary, Cornelia M. Wilson, Dorothee Staiger, Naeem Syed
Summary: Plants utilize gene regulatory mechanisms to adapt to environmental challenges. This study reveals that stochastic changes in DNA methylation can modulate nucleosome occupancy and alternative splicing (AS) in response to cold stress, thus influencing plant metabolism and stress adaptation.
Article
Biotechnology & Applied Microbiology
Shuting Lin, Soojin Yi, Peng Qiu
Summary: The relationship between DNA methylation and alternative splicing was examined in this study using multiple omics data types from TCGA. The study revealed significant associations between CpG sites and exon expression, consistent across different cancer contexts. CpG sites correlated with exon expression were also found to be more likely to be associated with patient survival outcomes. Furthermore, CpG sites were shown to have a stronger correlation with exon expression than with the expression of isoforms harboring the corresponding exons.
Article
Gastroenterology & Hepatology
Ming Zhang, Can Chen, Zequn Lu, Yimin Cai, Yanmin Li, Fuwei Zhang, Yizhuo Liu, Shuoni Chen, Heng Zhang, Shuhui Yang, Hui Gen, Yuan Jiang, Caibo Ning, Jinyu Huang, Wenzhuo Wang, Linyun Fan, Yi Zhang, Meng Jin, Jinxin Han, Zhen Xiong, Ming Cai, Jiuyang Liu, Chaoqun Huang, Xiaojun Yang, Bin Xu, Heng Li, Bin Li, Xu Zhu, Yongchang Wei, Ying Zhu, Jianbo Tian, Xiaoping Miao
Summary: This study provides a comprehensive functional analysis of splicing quantitative trait loci (sQTLs) in cancer and specifically in colorectal cancer (CRC). The researchers identified genetic variants that control messenger RNA splicing and examined their association with CRC risk. They also conducted biological experiments to investigate the potential mechanisms of these sQTLs and target genes. The study highlights the role of sQTLs in cancer susceptibility and suggests their potential as biomarkers and therapeutic targets.
Article
Plant Sciences
Zhipeng Yu, Xia Huang, Shuhan Wen, Haijuan Cao, Nan Wang, Shihua Shen, Mingquan Ding
Summary: This study reveals that the paper mulberry undergoes a substantial number of alternative splicing events in response to cold stress, with significant enrichment in starch and sucrose metabolism and circadian rhythm pathways. The differential spliced genes also showed differential expression, suggesting a coordinated regulation between gene alternative splicing and expression. Additionally, DNA methylation may play a role in governing gene splicing.
Article
Biotechnology & Applied Microbiology
Saurabh Chaudhary, Ibtissam Jabre, Naeem H. Syed
Summary: This study investigates the influence of stable and temperature-dependent variations in DNA methylation and nucleosome occupancy on alternative splicing in plants using an epigenetic Recombinant Inbred Line and the parental ecotype Columbia. The results show significant epigenetic differences between the two lines in response to normal and cold temperatures, affecting gene expression levels and alternative splicing. The patterns of DNA methylation and nucleosome levels around intron-exon boundaries are shown to modulate alternative splicing in Arabidopsis.
Article
Biology
Ling Wang, Lei Wang, Meilian Tan, Linhai Wang, Wei Zhao, Jun You, Lijun Wang, Xingchu Yan, Wei Wang
Summary: This study analysed the DNA methylation patterns and gene transcription and splicing changes in linseed under drought stress. The study found that drought stress significantly increased the occurrence of intron-retention and alternative 3' splice site events. The study also revealed that gene body methylation plays an important role in the AS regulation of specific genes.
BIOLOGICAL RESEARCH
(2023)
Article
Plant Sciences
Peng Tian, Zeteng Lin, Dongbo Lin, Shuangyu Dong, Jianzi Huang, Tengbo Huang
Summary: In response to phosphate starvation, tomato seedlings showed a slight increase in overall DNA methylation levels, with millions of differentially methylated cytosines and hundreds of differentially methylated regions. Thousands of genes displayed differential expression and alternative splicing under phosphate-deficient conditions, with differentially methylated cytosines more abundant in non-expressed genes. Additionally, DNA methylation changes weakly correlated with transcription changes, but not with alternative splicing events.
Review
Oncology
Adrian Casas-Benito, Sonia Martinez-Herrero, Alfredo Martinez
Summary: Approximately a century ago, Otto Warburg discovered that cancer cells use a different metabolism called aerobic glycolysis or the Warburg effect. This metabolism allows cancer cells to produce more ATP and promotes cancer progression. Succinate, a Krebs cycle intermediate, has been found to have protumoral functions in cancer and could be a potential target for cancer therapy. However, further research is needed to explore its potential in cancer prevention and treatment.
Article
Horticulture
Ding-Ding Zuo, Guang-Qi He, Hao-Ting Sun, Da-Long Guo
Summary: Hydrogen peroxide, methylation and alternative splicing have important regulatory roles in fruit development. This study analyzed the alternative splicing events during grape berry development under hydrogen peroxide treatment and control conditions. It was found that there were stage-specific regulations of alternative splicing and more events occurred at the early stages of berry development. Additionally, there were significant differences in alternative splicing events between the treatment and control, with some genes associated with methylation modifications.
SCIENTIA HORTICULTURAE
(2023)
Article
Chemistry, Multidisciplinary
Shengnan Liu, Ziru Sun, Min Liang, Weijie Song, Ru Zhang, Yunli Shi, Yujun Cui, Qingzhi Gao
Summary: This study uncovers the unexpected role of corannulene pi-bowls as an effective anticancer agent for selective tumor targeting mediated by the Warburg effect. The study also reveals that corannulene pi-bowls exploit tumor-specific glucose transporter GLUT1 for targeted cell delivery and intra-tumoral accumulation.
Review
Biochemistry & Molecular Biology
Yuanjiao Zhang, Jinjun Qian, Chunyan Gu, Ye Yang
Summary: The study systematically describes the abnormal regulation and functions of alternative splicing in tumors, as well as introduces therapeutic strategies targeting splicing catalysis and regulatory proteins. Further research is needed to fully understand the association between alternative splicing and cancer.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2021)
Review
Genetics & Heredity
Kiran Kumar Kolathur
Summary: Alternative splicing is crucial for enhancing proteome complexity in higher eukaryotes, with almost all multi intron-containing genes undergoing AS in humans. RNA polymerase II plays a crucial role in coordinating transcription and pre-mRNA splicing. Specific epigenetic changes at promoter regions may regulate alternative splicing.
Article
Oncology
Arpankumar Choksi, Apoorva Parulekar, Richa Pant, Vibhuti Kumar Shah, Ramakrishna Nimma, Priyanka Firmal, Smriti Singh, Gopal C. Kundu, Sanjeev Shukla, Samit Chattopadhyay
Summary: The study demonstrates that SMAR1 inhibits the Warburg effect by promoting PKM1 expression over PKM2 in breast cancer cells. It also shows that SMAR1 deacetylates PTBP1, leading to reduced enrichment of PTBP1 on PKM pre-mRNA and suppression of cancer cell metabolism and tumorigenesis. Additionally, SMAR1 suppresses tumor formation in vivo in a PKM2-dependent manner.
CANCER & METABOLISM
(2021)
Article
Biochemistry & Molecular Biology
Jiali Yu, Michael D. Green, Shasha Li, Yilun Sun, Sara N. Journey, Jae Eun Choi, Syed Monem Rizvi, Angel Qin, Jessica J. Waninger, Xueting Lang, Zoey Chopra, Issam El Naqa, Jiajia Zhou, Yingjie Bian, Long Jiang, Alangoya Tezel, Jeremy Skvarce, Rohan K. Achar, Merna Sitto, Benjamin S. Rosen, Fengyun Su, Sathiya P. Narayanan, Xuhong Cao, Shuang Wei, Wojciech Szeliga, Linda Vatan, Charles Mayo, Meredith A. Morgan, Caitlin A. Schonewolf, Kyle Cuneo, Ilona Kryczek, Vincent T. Ma, Christopher D. Lao, Theodore S. Lawrence, Nithya Ramnath, Fei Wen, Arul M. Chinnaiyan, Marcin Cieslik, Ajjai Alva, Weiping Zou
Summary: Liver metastases diminish the efficacy of immunotherapy by siphoning activated CD8(+) T cells from systemic circulation, creating systemic immune desert. Combining liver-directed radiotherapy with immunotherapy can promote systemic antitumor immunity.
Article
Oncology
Arpankumar Choksi, Apoorva Parulekar, Richa Pant, Vibhuti Kumar Shah, Ramakrishna Nimma, Priyanka Firmal, Smriti Singh, Gopal C. Kundu, Sanjeev Shukla, Samit Chattopadhyay
Summary: The study demonstrates that SMAR1 inhibits the Warburg effect by promoting PKM1 expression over PKM2 in breast cancer cells. It also shows that SMAR1 deacetylates PTBP1, leading to reduced enrichment of PTBP1 on PKM pre-mRNA and suppression of cancer cell metabolism and tumorigenesis. Additionally, SMAR1 suppresses tumor formation in vivo in a PKM2-dependent manner.
CANCER & METABOLISM
(2021)
Review
Cell Biology
Subhashis Natua, Shruti Ganesh Dhamdhere, Srinivas Abhishek Mutnuru, Sanjeev Shukla
Summary: The interaction between heterogeneous cancer cells within a tumor mass and the surrounding microenvironment shapes cancer pathophysiology, affecting immune tolerance, angiogenesis, metastasis, and therapy resistance. This dynamic interaction involves a dramatic reconstruction of the transcriptomic landscape of tumors by altering gene readout synthesis, modifications, stability, and processing.
WILEY INTERDISCIPLINARY REVIEWS-RNA
(2022)
Article
Multidisciplinary Sciences
Arun Prakash Mishra, Suzanne A. Hartford, Sounak Sahu, Kimberly Klarmann, Rajani Kant Chittela, Kajal Biswas, Albert B. Jeon, Betty K. Martin, Sandra Burkett, Eileen Southon, Susan Reid, Mary E. Albaugh, Baktiar Karim, Lino Tessarollo, Jonathan R. Keller, Shyam K. Sharan
Summary: The presence of homologous chromosomes in close proximity to the DNA double strand breaks compensates for the defect in the interaction between tumor suppressor BRCA2 and DSS1, allowing for normal RAD51 recruitment during meiosis.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Tarun Mishra, Vipin Bhardwaj, Neha Ahuja, Pallavi Gadgil, Pavitra Ramdas, Sanjeev Shukla, Ajit Chande
Summary: Strategies to modulate cellular DNA repair pathways have great potential for enhancing the efficiency of CRISPR-Cas9 genome editing. This study describes a reporter-based assay for measuring loss-of-function editing by CRISPR-Cas9 and identifies a small molecule, Repsox, that enhances editing efficiency. Repsox consistently increased CRISPR-Cas9 editing in various cell lines and primary cells, and enabled the generation of HIV-1-resistant cells with high efficiency in human CD4(+) T cells.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Biology
Tarun Mishra, Rishikesh Dalavi, Garima Joshi, Atul Kumar, Pankaj Pandey, Sanjeev Shukla, Ram K. Mishra, Ajit Chande
Summary: Emerging SARS-CoV-2 variants have raised concerns about breakthrough infections. A study sequenced and characterized the spike gene in breakthrough infections associated with the B.1.617 sublineage. The study found that specific spike mutations, such as E156G/Delta 157-158, contributed to increased infectivity and reduced sensitivity to vaccine-induced antibodies.
LIFE SCIENCE ALLIANCE
(2022)
Article
Genetics & Heredity
Bing Xia, Kajal Biswas, Tzeh K. Foo, Thiago T. Gomes, Maximilian Riedel-Topper, Eileen Southon, Zhihua Kang, Yanying Huo, Susan Reid, Stacey Stauffer, Weiyin Zhou, Bin Zhu, Hela Koka, Sally Yepes, Seth A. Brodie, Kristine Jones, Aurelie Vogt, Bin Zhu, Brian Carter, Neal D. Freedman, Belynda Hicks, Meredith Yeager, Stephen J. Chanock, Fergus Couch, Dilys M. Parry, Alvaro N. Monteiro, Alisa M. Goldstein, Marcelo A. Carvalho, Shyam K. Sharan, Xiaohong R. Yang
Summary: A study identified rare germline variants in PALB2 and BRCA2 genes that are associated with chordoma susceptibility. These genes play essential roles in homologous recombination and tumor suppression. The study also found a significantly increased burden of rare variants in both genes in chordoma cases compared to population controls. Experimental assays showed that some of these variants affected HR function. These findings contribute to our understanding of chordoma etiology and suggest potential therapeutic options for chordoma patients, such as PARP-1 inhibitors.
Article
Medicine, Research & Experimental
Shimaa Sherif, Raghvendra Mall, Hossam Almeer, Adviti Naik, Abdulaziz Al Homaid, Remy Thomas, Jessica Roelands, Sathiya Narayanan, Mahmoud Gasim Mohamed, Shahinaz Bedri, Salha Bujassoum Al-Bader, Kulsoom Junejo, Davide Bedognetti, Wouter Hendrickx, Julie Decock
Summary: We identified an immune-related 3-lncRNA signature with prognostic connotation in multiple solid cancer types, which performed equally well and in some cases better than the 20-gene ICR signature, indicating that it could be used as a minimal informative signature for clinical implementation.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Neelesh C. Reddy, Rajib Molla, Pralhad Namdev Joshi, T. K. Sajeev, Ipsita Basu, Jyotsna Kawadkar, Neetu Kalra, Ram Kumar Mishra, Suman Chakrabarty, Sanjeev Shukla, Vishal Rai
Summary: The authors report a method using cysteine-based chemoselective Linchpin Directed site-selective Modification of lysine residue in a protein, which provides high-level control over reactivity, chemoselectivity, site-selectivity, modularity, dual-probe installation, and protein-selectivity. The method offers protein selectivity by targeting a single lysine residue of a single protein in a complex biomolecular mixture, and it is useful for precision engineering of proteins.
NATURE COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
Kalyani Thakur, T. K. Sajeev, Shivam Kumar Singh, V. Ragendu, Dattatraya Gautam Rawale, Srinivasa Rao Adusumalli, Neetu Kalra, Sanjeev Shukla, Ram Kumar Mishra, Vishal Rai
BIOCONJUGATE CHEMISTRY
(2022)
Review
Oncology
Kajal Biswas, Altaf Mohammed, Shyam K. Sharan, Robert H. Shoemaker
Summary: Advances in molecular diagnostics have improved the diagnosis and understanding of hereditary cancers. Preclinical experimental models, such as genetically engineered mouse (GEM) models, play a crucial role in studying and preventing cancer in high-risk populations.
Article
Multidisciplinary Sciences
Pooja Yadav, Anchala Pandey, Parik Kakani, Srinivas Abhishek Mutnuru, Atul Samaiya, Jharna Mishra
Summary: Alternative splicing of VEGFA generates different isoforms with unique roles in tumor angiogenesis. Our research showed that the splicing factor SRSF2 promotes the formation of anti-angiogenic VEGFA-165b isoform under normal conditions by including exon-8b and inhibiting the expression of pro-angiogenic VEGFA-165a by excluding exon-8a. Under hypoxic conditions, SRSF2 is downregulated by miR-222-3p induced by HIF1 alpha, leading to exon-8b exclusion and reduced VEGFA-165b expression, while increased CTCF recruitment and exon-8a inclusion enhance the expression of VEGFA-165a.
Article
Oncology
Madhura R. Pandkar, Atul Samaiya, Sanjeev Shukla
Summary: This study finds that an enhanced rate of aerobic glycolysis supports the expression of c-Myc through histone lactylation, which further upregulates SRSF10 to drive alternative splicing in breast cancer cells. Restricting the activity of critical glycolytic enzymes affects the c-Myc-SRSF10 axis and reduces the proliferation of breast cancer cells. These findings provide new insights into the molecular mechanisms of breast tumorigenesis and suggest that targeting glycolytic rate may be a potential therapeutic strategy for breast cancer.
TRANSLATIONAL ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Madhura R. Pandkar, Adarsh Raveendran, Kajal Biswas, Srinivas Abhishek Mutnuru, Jharna Mishra, Atul Samaiya, Tyler Malys, Alexander Y. Mitrophanov, Shyam K. Sharan, Sanjeev Shukla
Summary: The study reveals that non-canonical PKM2 mediates the upregulation of PFKFB3 under hypoxia by facilitating the enrichment of HIF-1α and p300 at PFKFB3 hypoxia-responsive elements. The absence of PKM2 promotes the occupancy of HIF-2α and a poised state of PFKFB3 HREs-associated chromatin, which restricts HIF-2α from inducing PFKFB3 while maintaining its basal-level expression through multiple histone modifications. Shikonin has been demonstrated to inhibit nuclear translocation of PKM2 and effectively suppress PFKFB3 expression, leading to substantial growth inhibition of TNBC patient-derived organoids and MCF7 cells-derived xenograft tumors.
Review
Biochemistry & Molecular Biology
Flavio R. Palma, Benjamin N. Gantner, Marcelo J. Sakiyama, Cezar Kayzuka, Sanjeev Shukla, Riccardo Lacchini, Brian Cunniff, Marcelo G. Bonini
Summary: In eukaryotic cells, mitochondria are traditionally viewed as the primary organelles responsible for ATP generation under normoxic conditions. However, recent studies have shown that mitochondrial ROS play important signaling functions in cellular adaptation and stress resistance. Contrary to previous beliefs, ROS production is not merely a by-product of dysfunctional mitochondria, but an essential component in cellular adaptation triggered by important stressors.
