Article
Oncology
Jagyeong Oh, Davide Pradella, Yoonseong Kim, Changwei Shao, Hairi Li, Namjeong Choi, Jiyeon Ha, Anna Di Matteo, Xiang-Dong Fu, Xuexiu Zheng, Claudia Ghigna, Haihong Shen
Summary: Aberrant alternative splicing (AS) regulation is crucial in breast cancer development, progress, and resistance to therapy. Our study identified dysregulated AS events in breast cancer cells, shedding light on the molecular mechanisms underlying malignant transformation. Analysis revealed that aberrantly regulated AS events in cancer tissues encode for regions with high flexibility and potential for modifications, impacting breast cancer biology.
Article
Cell Biology
Jagyeong Oh, Davide Pradella, Changwei Shao, Hairi Li, Namjeong Choi, Jiyeon Ha, Sonia Ruggiero, Xiang-Dong Fu, Xuexiu Zheng, Claudia Ghigna, Haihong Shen
Summary: Aberrant alternative splicing in breast cancer is linked to disease progression, metastasis, and patient survival. High-metastatic breast cancer cells exhibit different AS choices in genes related to cancer progression compared to low-metastatic cells. Analysis reveals novel AS features in metastatic breast tumors.
Review
Biochemistry & Molecular Biology
Subhashis Natua, Cheemala Ashok, Sanjeev Shukla
Summary: Maintenance of oxygen homeostasis is crucial for the existence of multicellular organisms, and disruption of this homeostasis can lead to pathological hypoxia in various conditions. Cellular adaptations include changes in gene expression, post-transcriptional modification of gene products, bioenergetics, and metabolism under hypoxic conditions. Hypoxia-induced alternative splicing events are associated with diseases like cancer, cardiovascular diseases, and neurological disorders, offering potential strategies for novel translational diagnosis and therapeutic interventions.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Oncology
Jamal Elhasnaoui, Giulio Ferrero, Valentina Miano, Santina Cutrupi, Michele De Bortoli
Summary: This study reveals a novel mechanism of gene regulation mediated by estrogen receptor alpha in breast cancer cells, involving the control of RNA-binding protein expression and effects on isoform usage and alternative splicing. These regulatory mechanisms play a significant role in cell proliferation and epithelial-to-mesenchymal transition in breast cancer.
Review
Oncology
Jiawei Ouyang, Yijie Zhang, Fang Xiong, Shanshan Zhang, Zhaojian Gong, Qijia Yan, Yi He, Fang Wei, Wenling Zhang, Ming Zhou, Bo Xiang, Fuyan Wang, Xiaoling Li, Yong Li, Guiyuan Li, Zhaoyang Zeng, Can Guo, Wei Xiong
Summary: This article introduces the definition of alternative splicing in eukaryotes and its importance in cancer development. Alternative splicing is a transcription process that allows coding genes to be translated into multiple proteins with different functions. Alterations in splicing mechanisms may lead to changes in the splicing patterns of cancer-related genes.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Review
Oncology
Antoine Bernard, Romain Boidot, Frederique Vegran
Summary: This article presents the role and mechanism of alternative splicing in cancer cells and immune cells. Alternative splicing is an important mechanism that can generate multiple proteins from a single gene. In normal cells, alternative splicing is involved in the regulation of cellular behavior. However, in cancer, alternative splicing is dysregulated and contributes to the characteristics of tumor cells.
Review
Oncology
Weronika Wojtys, Magdalena Oron
Summary: The development of RNA sequencing methods enables us to study and understand the aberrant pre-mRNA splicing in tumors. Altered splicing patterns affect various aspects of cancer development and are influenced by driver oncogenes. In turn, aberrant splicing activates key oncogenes and oncogenic pathways. Cancer research aims to improve diagnosis and treatment, and targeting alternative splicing mechanisms in the context of driver oncogenes presents potential therapeutic opportunities.
Article
Oncology
Zhihui Dou, Xuetian Zhang, Wei Su, Taotao Zhang, Fei Ye, Dapeng Zhao, Qiang Li, Hong Zhang, Cuixia Di, Xiaohua Chen
Summary: This study evaluated and investigated the therapeutic potential of Indisulam in human cervical cancer cells. The results showed that Indisulam inhibited tumor growth, disrupted transcriptional regulation pathways related to mRNA splicing and apoptosis, and caused mis-splicing of RNA transcripts including p73 isoforms and UDelta;Np73 and TAp73. Indisulam increased TAp73 expression and triggered mitochondrial apoptosis, independent of p53 status, suggesting it as a potential strategy for p53-disrupted cancers.
AMERICAN JOURNAL OF CANCER RESEARCH
(2023)
Article
Cell Biology
Yuka Ikeda-Iwabu, Yoshiaki Taniyama, Naruto Katsuragi, Fumihiro Sanada, Nobutaka Koibuchi, Kana Shibata, Kenzo Shimazu, Hiromi Rakugi, Ryuichi Morishita
Summary: The study found that POSTN in cancer cells can be detected using an Ex17 antibody but not an Ex12 antibody. A short fragment of POSTN with exon 17 was identified in the fraction secreted from fibroblasts. POSTN with exon 17 specifically bound to wnt3a, and this binding was inhibited by the Ex17 antibody.
Article
Biochemistry & Molecular Biology
Kamila Kwiecien, Pawel Majewski, Maciej Bak, Piotr Brzoza, Urszula Godlewska, Izabella Skulimowska, Joanna Cichy, Mateusz Kwitniewski
Summary: This study identified novel transcript variants of mouse Rarres2 and found limited role for alternative splicing in generating chemerin isoform diversity, except in brown adipose tissue. Only one transcript variant of human RARRES2 was present in liver and adipose tissue.
MOLECULAR BIOLOGY REPORTS
(2023)
Article
Oncology
Laurynas Vilys, Inga Peciuliene, Egle Jakubauskiene, Ruta Zinkeviciute, Yuichi Makino, Arvydas Kanopka
Summary: The splicing machinery is crucial for cellular adaptability and hypoxia can alter RNA splicing, leading to the formation of different Fas mRNA isoforms.
EXPERIMENTAL CELL RESEARCH
(2021)
Article
Oncology
Pihua Han, Jingjun Zhu, Guang Feng, Zizhang Wang, Yanni Ding
Summary: This study identified survival-associated AS events and signatures that can help predict the survival outcomes of patients with BRCA. Additionally, constructed SF-AS networks in BRCA can reveal the underlying regulatory mechanisms in BRCA.
Article
Cell Biology
Rui Wu, Junfeng Zhan, Bo Zheng, Zhen Chen, Jianbo Li, Changrong Li, Rong Liu, Xinhua Zhang, Xiaoyan Huang, Mengcheng Luo
Summary: The study reveals that SYMPK plays a critical role in male germ cells development, and its knockout leads to male infertility in mice. Deletion of SYMPK affects spermatogenesis and meiotic progression by influencing alternative splicing and gene expression.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Yun-Song Yang, Xi Jin, Qin Li, Yi-Yu Chen, Fenfang Chen, Hena Zhang, Ying Su, Yi Xiao, Gen-Hong Di, Yi-Zhou Jiang, Shenglin Huang, Zhi-Ming Shao
Summary: This study explored the transcription variation landscape in triple-negative breast cancers (TNBCs) and identified a crucial oncogenic transcript MARCO-TST, which is associated with tumor progression and poor prognosis in TNBC patients. MARCO-TST enhances the stability of HIF-1 alpha by interacting with PLOD2, leading to metabolic dysregulation and the formation of a hypoxic tumor microenvironment in TNBC.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Oncology
Yasushi Mochizuki, Ryo Funayama, Matsuyuki Shirota, Yuna Kikukawa, Masahiro Ohira, Hideaki Karasawa, Minoru Kobayashi, Shinobu Ohnuma, Michiaki Unno, Keiko Nakayama
Summary: This study showed differential splicing of microexons in colorectal cancer, with 21 genes enriched in gene ontology terms related to cell adhesion and migration. RNA interference experiments identified RBFOX2 and PTBP1 as splicing regulators in CRC cells. Changes in microexon splicing patterns were associated with CRC metastasis, likely influenced by altered expression of RBFOX2 and PTBP1.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Biochemistry & Molecular Biology
Quy Xiao Xuan Lin, Denis Thieffry, Sudhakar Jha, Touati Benoukraf
NUCLEIC ACIDS RESEARCH
(2020)
Article
Oncology
Joanna R. Sinnakannu, Kian Leong Lee, Shanshan Cheng, Jia Li, Mengge Yu, Siew Peng Tan, Clara Chong Hui Ong, Huihua Li, Hein Than, Olga Anczukow-Camarda, Adrian R. Krainer, Xavier Roca, Steven G. Rozen, Jabed Iqbal, Henry Yang, Charles Chuah, Sin Tiong Ong
Article
Multidisciplinary Sciences
Sze Jing Tang, Haoqing Shen, Omer An, HuiQi Hong, Jia Li, Yangyang Song, Jian Han, Daryl Jin Tai Tay, Vanessa Hui En Ng, Fernando Bellido Molias, Ka Wai Leong, Priyankaa Pitcheshwar, Henry Yang, Leilei Chen
NATURE COMMUNICATIONS
(2020)
Article
Hematology
Tun Kiat Ko, Asif Javed, Kian Leong Lee, Thushangi N. Pathiraja, Xingliang Liu, Simeen Malik, Sheila Xinxuan Soh, Xiu Ting Heng, Naoto Takahashi, Joanna H. J. Tan, Ravi Bhatia, Alexis J. Khng, Wee-Joo Chng, Yee Yen Sia, David A. Fruman, King Pan Ng, Zhu En Chan, Kim Jiajing Xie, Qiangze Hoi, Cheryl Xueli Chan, Audrey S. M. Teo, Oscar Velazquez Camacho, Wee Yang Meah, Chiea Chuen Khor, Chin Thing J. Ong, Wei Jia W. Soon, Patrick Tan, Pauline C. Ng, Charles Chuah, Axel M. Hillmer, S. Tiong Ong
Article
Gastroenterology & Hepatology
Yangyang Song, Omer An, Xi Ren, Tim Hon Man Chan, Daryl Jin Tai Tay, Sze Jing Tang, Jian Han, HuiQi Hong, Vanessa Hui En Ng, Xinyu Ke, Haoqing Shen, Priyankaa Pitcheshwar, Jaymie Siqi Lin, Ka Wai Leong, Fernando Bellido Molias, Henry Yang, Dennis Kappei, Leilei Chen
Summary: RNA editing lowers the level of edited COPA gene in tumor samples, leading to the transformation of COPA protein from a cancer-promoting form to a cancer-suppressive form. The loss of edited COPA promotes the development of liver cancer.
JOURNAL OF HEPATOLOGY
(2021)
Article
Multidisciplinary Sciences
Jian Han, Omer An, HuiQi Hong, Tim Hon Man Chan, Yangyang Song, Haoqing Shen, Sze Jing Tang, Jaymie Siqi Lin, Vanessa Hui En Ng, Daryl Jin Tai Tay, Fernando Bellido Molias, Priyankaa Pitcheshwar, Hui Qing Tan, Henry Yang, Leilei Chen
Article
Multidisciplinary Sciences
Patty Sachamitr, Jolene C. Ho, Felipe E. Ciamponi, Wail Ba-Alawi, Fiona J. Coutinho, Paul Guilhamon, Michelle M. Kushida, Florence M. G. Cavalli, Lilian Lee, Naghmeh Rastegar, Victoria Vu, Maria Sanchez-Osuna, Jasmin Coulombe-Huntington, Evgeny Kanshin, Heather Whetstone, Mathieu Durand, Philippe Thibault, Kirsten Hart, Maria Mangos, Joseph Veyhl, Wenjun Chen, Nhat Tran, Bang-Chi Duong, Ahmed M. Aman, Xinghui Che, Xiaoyang Lan, Owen Whitley, Olga Zaslaver, Dalia Barsyte-Lovejoy, Laura M. Richards, Ian Restall, Amy Caudy, Hannes L. Rost, Zahid Quyoom Bonday, Mark Bernstein, Sunit Das, Michael D. Cusimano, Julian Spears, Gary D. Bader, Trevor J. Pugh, Mike Tyers, Mathieu Lupien, Benjamin Haibe-Kains, H. Artee Luchman, Samuel Weiss, Katlin B. Massirer, Panagiotis Prinos, Cheryl H. Arrowsmith, Peter B. Dirks
Summary: The study suggests that PRMT5 inhibitors can block the growth of patient-derived glioblastoma stem cell cultures in vitro and in vivo, indicating that PRMT5 inhibition may be a useful therapeutic strategy.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Shojiro Kitajima, Wendi Sun, Kian Leong Lee, Jolene Caifeng Ho, Seiichi Oyadomari, Takashi Okamoto, Hisao Masai, Lorenz Poellinger, Hiroyuki Kato
Summary: The UTX/KDM6A gene encodes a major histone H3 lysine 27 (H3K27) demethylase and is frequently mutated in human cancers. The pharmacological inhibitor GSK-J4 induces the expression of ATF4 protein and its target genes. The inhibition of UTX partially leads to ATF4 induction, suggesting a potential role of UTX in regulating cancer formation through the HRI-ATF4 axis.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Kwok Kin Lee, Deepa Rajagopalan, Shreshtha Sailesh Bhatia, Roberto Tirado-Magallanes, Wee Joo Chng, Sudhakar Jha
Summary: TRIP12 is associated with distant metastasis-free survival in breast cancer, indicating a potential role in inhibiting metastasis in this study. Depletion of TRIP12 leads to EMT shift and mesenchymal traits in cells, while ectopic expression of TRIP12 increases cell sensitivity to anoikis.
CELL DEATH DISCOVERY
(2021)
Letter
Oncology
Kian Leong Lee, Tun Kiat Ko, Nicole Y. L. Saw, Asif Javed, Axel M. Hillmer, Charles Chuah, Vaidehi Krishnan, S. Tiong Ong
Article
Multidisciplinary Sciences
Jian Han, Omer An, Xi Ren, Yangyang Song, Sze Jing Tang, Haoqing Shen, Xinyu Ke, Vanessa Hui En Ng, Daryl Jin Tai Tay, Hui Qing Tan, Dennis Kappei, Henry Yang, Leilei Chen
Summary: DAP3 acts as a splicing modulator in cancer by coordinating splicing regulatory networks and causing mis-splicing events, which are associated with poor prognosis in multiple cancers.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Haoqing Shen, Omer An, Xi Ren, Yangyang Song, Sze Jing Tang, Xin-Yu Ke, Jian Han, Daryl Jin Tai Tay, Vanessa Hui En Ng, Fernando Bellido Molias, Priyankaa Pitcheshwar, Ka Wai Leong, Ker-Kan Tan, Henry Yang, Leilei Chen
Summary: This study demonstrates that ADARs play a significant role in regulating the circular transcriptome. ADARs can stabilize or destabilize circRNA secondary structures through editing, and also enhance the binding of RNA-binding proteins. These ADARs-regulated circRNAs are widely expressed in various cancers and have functional relevance to tumorigenesis.
NATURE COMMUNICATIONS
(2022)
Review
Oncology
Asad Mohammad, Sudhakar Jha
Summary: Epigenetic modifications, such as DNA methylation and histone modification, play a crucial role in cancer progression and metastasis. Inhibitors targeting deregulated enzymes can reverse these modifications and show promising results in cancer therapeutics.
Article
Hematology
Vaidehi Krishnan, Florian Schmidt, Zahid Nawaz, Prasanna Nori Venkatesh, Kian Leong Lee, Xi Ren, Zhu En Chan, Mengge Yu, Meera Makheja, Nirmala Arul Rayan, Michelle Gek Liang Lim, Alice Man Sze Cheung, Sudipto Bari, Wee Joo Chng, Hein Than, John Ouyang, Owen Rackham, Tuan Zea Tan, William Ying Khee Hwang, Charles Chuan, Shyam Prabhakar, S. Tiong Ong
Summary: Using single-cell RNA sequencing, we identified 8 significant features in the bone marrow of chronic myeloid leukemia patients that correlated with sensitivity or resistance to imatinib treatment. By employing machine learning, we accurately predicted imatinib response with over 80% accuracy, including no false positives for predicting blast crisis transformation. Patients with major molecular response exhibited a signature erythroid-specifying regulon, while those who progressed to transformation showed an inflammatory regulon.