Article
Cell Biology
Changan Zhao, Jiyu Miao, Ruifang Sun, Rui Liang, Wenhu Chen, Yi Gao, Xiaofei Wang, Shuiping Han, Wenbao Zhao, Ting Lei, Chen Huang
Summary: Gastric cancer (GC) is one of the major causes of cancer-related deaths worldwide, and there is a lack of specific biomarkers for early diagnosis and universally accepted therapy for advanced GC. This study found that lower levels of miR-5701 were associated with GC, and overexpression of miR-5701 inhibited GC cell proliferation and migration while promoting apoptosis. The study also identified FGFR2 as a target of miR-5701 in GC. Furthermore, experiments in mice showed that GC cells overexpressing miR-5701 had smaller tumors and fewer lung metastases. The study also revealed that MBD1 and HDAC3 directly inhibited miR-5701 expression, suggesting the potential use of exogenously administered miR-5701 or agents that elevate endogenous miR-5701 to inhibit GC and improve patient prognosis.
Article
Biochemistry & Molecular Biology
Li-Rong Ren, Ru-Bin Yao, Shi-Yong Wang, Xiang-Dong Gong, Ji-Tao Xu, Kai-Shun Yang
Summary: It was found that miR-27a-3p promotes osteoblast differentiation by mediating the CRY2/ERK1/2 axis, suggesting it could be a new target for treating osteoporosis.
MOLECULAR MEDICINE
(2021)
Article
Biotechnology & Applied Microbiology
Soeren S. Huettner, Henriette Henze, Dana Elster, Philipp Koch, Ursula Anderer, Bjoern von Eyss, Julia von Maltzahn
Summary: The expression levels of the transcriptional repressor TRPS1 are specifically enhanced in the embryonal subtype of rhabdomyosarcoma, resulting in impaired myogenic differentiation and tumor growth. Reduction of TRPS1 levels may be a therapeutic approach to drive embryonal rhabdomyosarcoma cells into myogenic differentiation.
Article
Biochemistry & Molecular Biology
Susu Zhang, Jing Wang, Qi Liu, W. Hayes McDonald, Monica L. Bomber, Hillary M. Layden, Jacob Ellis, Scott C. Borinstein, Scott W. Hiebert, Kristy R. Stengel
Summary: Transcriptional control is a dynamic process that is challenging to study using traditional genetic methods. In this study, we used a chemical-genetic approach to quickly degrade the transcriptional activator PAX3-FOXO1 and investigated its mechanism of action. Our findings revealed that PAX3-FOXO1 is involved in regulating gene expression and maintaining chromatin accessibility and enhancer architecture.
Article
Agriculture, Multidisciplinary
Shi-Yong Zhu, Xue-Nan Li, Yi Zhao, Xue-Yan Dai, Jian-Ying Guo, Jin-Long Li
Summary: The study found that atrazine induced Foxo1 deficiency in the B cell zone of the spleen, leading to toxicity, while lycopene ameliorated atrazine-induced apoptosis in the B cell zone through regulating the miR-27a-3p/Foxo1 pathway. This research underscores the important role of lycopene in maintaining homeostasis during B cell maturation.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Chao Chen, Yu'e Liu, Hongxiang Wang, Xu Zhang, Yufeng Shi, Juxiang Chen
Summary: We investigated the role of FOXO1 and miR-506 in the progression and drug resistance of GBM. Through in vitro and in vivo experiments, we found that the FOXO1-miR-506 axis suppresses GBM cell invasion and migration and promotes chemosensitivity to TMZ, mediated by autophagy. We also discovered a negative feedback loop of FOXO1/miR-506/ETS1/FOXO1 in regulating invasiveness and chemosensitivity in GBM.
JOURNAL OF ZHEJIANG UNIVERSITY-SCIENCE B
(2023)
Article
Cell Biology
Wenyu Li, Qiongbin Zhu, Xiaoyan Xu, Xingyue Hu
Summary: The study found that miR-27a-3p can suppress cerebral ischemia-reperfusion injury by targeting FOXO1. In vitro experiments showed that OGD induced apoptosis and oxidative stress in HT22 cells, along with G1 arrest mediated by FOXO1/p27 Kip1 signaling. MiR-27a-3p mimics reversed these effects, and in vivo studies using a rat model also showed alleviation of CI/R symptoms with miR-27a-3p agomir treatment.
Article
Genetics & Heredity
Line J. Manceau, Julien E. Richard Albert, Pier-Luigi J. Lollini, Maxim V. C. E. Greenberg, Pascale J. Gilardi-Hebenstreit, Vanessa E. Ribes
Summary: The chimeric proteins PAX3-FOXO1 and PAX7-FOXO1, derived from chromosomal translocations, exhibit distinct genomic occupancy and transcriptional activity, leading to different pathological manifestations in alveolar rhabdomyosarcoma.
Article
Oncology
Christine M. Heske, Yueh-Yun Chi, Rajkumar Venkatramani, Minjie Li, Michael A. Arnold, Roshni Dasgupta, Susan M. Hiniker, Douglas S. Hawkins, Leo Mascarenhas
Summary: In patients with localized, FOXO1 fusion-positive RMS, clinical factors such as age at diagnosis and tumor size can impact survival outcomes, with older age and larger tumors being adverse prognostic factors for EFS. Patients with both older age and large tumor size experience significantly inferior outcomes.
Article
Multidisciplinary Sciences
Takuyo Kanayama, Mitsuru Miyachi, Yohei Sugimoto, Shigeki Yagyu, Ken Kikuchi, Kunihiko Tsuchiya, Tomoko Iehara, Hajime Hosoi
Summary: The study found that PAX3-FOXO1 is associated with B7-H3 in alveolar rhabdomyosarcoma, with PAX3-FOXO1 positively regulating B7-H3 expression. Both are involved in multiple pathways related to aggressiveness in ARMS, such as cell migration and myogenic differentiation.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Shivendra Singh, Ahmed Abu-Zaid, Hongjian Jin, Jie Fang, Qiong Wu, Tingting Wang, Helin Feng, Waise Quarni, Ying Shao, Lily Maxham, Alireza Abdolvahabi, Mi-Kyung Yun, Sivaraja Vaithiyalingam, Haiyan Tan, John Bowling, Victoria Honnell, Brandon Young, Yian Guo, Richa Bajpai, Shondra M. Pruett-Miller, Gerard C. Grosveld, Mark Hatley, Beisi Xu, Yiping Fan, Gang Wu, Eleanor Y. Chen, Taosheng Chen, Peter W. Lewis, Zoran Rankovic, Yimei Li, Andrew J. Murphy, John Easton, Junmin Peng, Xiang Chen, Ruoning Wang, Stephen W. White, Andrew M. Davidoff, Jun Yang
Summary: This study identifies KDM4B as a therapeutic vulnerability for PAX3-FOXO1(+) RMS. Inhibition of KDM4B delays tumor growth and suppresses the expression of core oncogenic transcription factors, causing epigenetic alterations of PAX3-FOXO1-governed superenhancers.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Medicine, Research & Experimental
Yong-Li Wang, Dan Ren, Jin-Long Lu, He Jiang, Jia-Zhang Wei, Jiao Lan, Fei Liu, Shen-Hong Qu
Summary: In nasopharyngeal carcinoma (NPC), CREB1 and SRGN are increased while miR-148a-5p is decreased. Silencing of SRGN and CREB1, and miR-148a-5p overexpression represses NPC tumor progression. The authors show that CREB1 promotes SRGN expression by targeting its promoter. In NPC, FoxO1 binds to miR-148a-5p, and miR-148a-5p targets CREB1. FoxO1 knockdown abolishes the downregulation of CREB1 and SRGN induced by STAT3 silencing. In summary, STAT3 regulates SRGN and promotes the growth and metastasis of NPC through the FoxO1-miR-148a-5p-CREB1 axis.
LABORATORY INVESTIGATION
(2022)
Article
Biochemistry & Molecular Biology
Matteo Cassandri, Silvia Pomella, Alessandra Rossetti, Francesco Petragnano, Luisa Milazzo, Francesca Vulcano, Simona Camero, Silvia Codenotti, Francesca Cicchetti, Roberto Maggio, Claudio Festuccia, Giovanni Luca Gravina, Alessandro Fanzani, Francesca Megiorni, Marialuigia Catanoso, Cinzia Marchese, Vincenzo Tombolini, Franco Locatelli, Rossella Rota, Francesco Marampon
Summary: The study evaluated the effects of MS-275 in combination with radiation therapy on RMS cells, showing that MS-275 could enhance radio-sensitivity and affect cell growth and DNA repair mechanisms through multiple pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Mingyan Xu, Junling Zhang, Xuemei Lu, Fan Liu, Songlin Shi, Xiaoling Deng
Summary: SMARCA4 is highly upregulated in oral squamous cell carcinoma (OSCC) tissues, promoting cell invasion and tumor growth. Mechanistic studies reveal that miR-199a-5p-regulated SMARCA4 promotes tumor cell invasion and metastasis through epithelial-mesenchymal transition (EMT). These findings provide insights into the role of SMARCA4 in OSCC and have important implications for therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Shiwei Xiao, Yigang Zuo, Yanan Li, Yinglong Huang, Shi Fu, Dongbo Yuan, Xuhua Qiao, Haifeng Wang, Jiansong Wang
Summary: In this study, it was found that HAGLROS is highly expressed in bladder cancer and is closely associated with pathological grade and clinical stage. HAGLROS can promote the growth and metastasis of bladder cancer. Moreover, HAGLROS acts as a microRNA sponge to positively regulate the expression of SPRR1B by sequestering miR-330-5p. These findings suggest that HAGLROS may serve as a potential biomarker for the diagnosis and treatment of bladder cancer.
FRONTIERS IN ONCOLOGY
(2022)
Meeting Abstract
Oncology
Ryan S. Chiang, Arya Ashok, Elizabeth Mauer, Alex Barrett, Christian R. Hoerner, Osama A. Khan, Chia-Sui Kao, Sumit Shah, Sandy Srinivas, Alice C. Fan, Ali Raza Khaki
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Palaniraja Thandapani, Andreas Kloetgen, Matthew T. Witkowski, Christina Glytsou, Anna K. Lee, Eric Wang, Jingjing Wang, Sarah E. LeBoeuf, Kleopatra Avrampou, Thales Papagiannakopoulos, Aristotelis Tsirigos, Iannis Aifantis
Summary: Deregulation of tRNA biogenesis plays a critical role in the pathogenesis of T cell acute lymphoblastic leukemia (T-ALL), with altered valine tRNA biogenesis enhancing mitochondrial bioenergetics and restricting dietary valine intake leading to decreased leukemia burden and increased survival. Additionally, genetic ablation or pharmacological inhibition of specific genes synergizes with valine restriction to reduce T-ALL growth.
Article
Medicine, General & Internal
Eric Wang, Xiaoli Mi, Meghan C. Thompson, Skye Montoya, Ryan Q. Notti, Jumana Afaghani, Benjamin H. Durham, Alex Penson, Matthew T. Witkowski, Sydney X. Lu, Jessie Bourcier, Simon J. Hogg, Caroline Erickson, Dan Cui, Hana Cho, Michael Singer, Tulasigeri M. Totiger, Sana Chaudhry, Mark Geyer, Alvaro Alencar, Adam J. Linley, M. Lia Palomba, Catherine C. Coombs, Jae H. Park, Andrew Zelenetz, Lindsey Roeker, Mary Rosendahl, Donald E. Tsai, Kevin Ebata, Barbara Brandhuber, David M. Hyman, Iannis Aifantis, Anthony Mato, Justin Taylor, Omar Abdel-Wahab
Summary: This study reveals new mutations in the BTK kinase domain and occasional mutations in downstream PLC gamma 2 in patients with chronic lymphocytic leukemia who developed resistance to the noncovalent BTK inhibitor pirtobrutinib. Despite the inactivity of BTK, alternative pathways of B-cell-receptor signaling were evident.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Narendra Bharathy, Megan M. Cleary, Jin-Ah Kim, Kiyo Nagamori, Kenneth A. Crawford, Eric Wang, Debarya Saha, Teagan P. Settelmeyer, Reshma Purohit, Damianos Skopelitis, Kenneth Chang, Jessica A. Doran, C. Ward Kirschbaum, Suriya Bharathy, Davis W. Crews, Matthew E. Randolph, Anthony N. Karnezis, Lisa Hudson-Price, Jyotsna Dhawan, Joel E. Michalek, Alessio Ciulli, Christopher R. Vakoc, Charles Keller
Summary: Rhabdomyosarcoma (RMS) is a common soft tissue sarcoma in children characterized by failed muscle precursor differentiation. The alveolar subtype (ARMS) has the worst prognosis and is in urgent need of treatment. Recent evidence suggests that epigenetic dysregulation plays a role in RMS. This study identifies SMARCA4/BRG1 as an important factor in ARMS tumor cell survival and a potential therapeutic target.
Article
Medicine, General & Internal
Taejoon Won, Megan K. Wood, David M. Hughes, Monica Talor, Zexu Ma, Jowaly Schneider, John T. Skinner, Beejan Asady, Erin Goerlich, Marc K. Halushka, Allison G. Hays, Deok-Ho Kim, Chirag R. Parikh, Avi Z. Rosenberg, Isabelle Coppens, Roger A. Johns, Nisha A. Gilotra, Jody E. Hooper, Andrew Pekosz, Daniela Cihakova
Summary: The article explains the copyright ownership and the license agreement it follows.
Article
Medicine, General & Internal
Timothy A. Yap, Arya Ashok, Jessica Stoll, Elizabeth Mauer, Vanessa M. Nepomuceno, Kimberly L. Blackwell, Judy E. Garber, Funda Meric-Bernstam
Summary: This study evaluates the prevalence of germline findings in cancer types lacking genetic testing guidelines. The results suggest that there may be clinical implications of germline mutations in these cancer types for patients and their at-risk family members.
Article
Oncology
Sisi Chen, Rahul S. Vedula, Antonio Cuevas-Navarro, Bin Lu, Simon J. Hogg, Eric Wang, Salima Benbarche, Katherine Knorr, Won Jun Kim, Robert F. Stanley, Hana Cho, Caroline Erickson, Michael Singer, Dan Cui, Steven Tittley, Benjamin H. Durham, Tatiana S. Pavletich, Elise Fiala, Michael F. Walsh, Daichi Inoue, Sebastien Monette, Justin Taylor, Neal Rosen, Frank McCormick, R. Coleman Lindsley, Pau Castel, Omar Abdel-Wahab
Summary: In this study, we found that impairing the proteolysis of noncanonical RAS GTPases RIT1 and MRAS through LZTR1 downregulation or leukemia-associated mutations stabilizing RIT1 enhances MAP kinase activation and promotes leukemogenesis. Reducing the abundance of GTP-bound KRAS and NRAS overcomes the resistance to FLT3 kinase inhibitors associated with LZTR1 downregulation in leukemia.
Article
Immunology
Matthew T. Witkowski, Soobeom Lee, Eric Wang, Anna K. Lee, Alexis Talbot, Chao Ma, Nikolaos Tsopoulidis, Justin Brumbaugh, Yaqi Zhao, Kathryn G. Roberts, Simon J. Hogg, Sofia Nomikou, Yohana E. Ghebrechristos, Palaniraja Thandapani, Charles G. Mullighan, Konrad Hochedlinger, Weiqiang Chen, Omar Abdel-Wahab, Justin Eyquem, Iannis Aifantis
Summary: Aifantis and colleagues used leukemic cell lines to identify novel regulators of CD19 expression in B-ALL. They found that the transcriptional activator ZNF143 plays a critical role in CD19 promoter activation, while the RNA-binding protein NUDT21 limits CD19 expression through the regulation of CD19 mRNA polyadenylation and stability. Deletion of NUDT21 in B-ALL cells increased CD19 expression and sensitivity to CAR-T and blinatumomab. Clinical findings showed that upregulation of NUDT21 coincided with CD19 loss in B-ALL patients at disease relapse.
Article
Oncology
Eric Wang, Jose Mario Bello Pineda, Won Jun Kim, Sisi Chen, Jessie Bourcier, Maximilian Stahl, Simon J. Hogg, Jan Phillipp Bewersdorf, Cuijuan Han, Michael E. Singer, Daniel Cui, Caroline E. Erickson, Steven M. Tittley, Alexander V. Penson, Katherine Knorr, Robert F. Stanley, Jahan Rahman, Gnana Krishnamoorthy, James A. Fagin, Emily Creger, Elizabeth McMillan, Chi-Ching Mak, Matthew Jarvis, Carine Bossard, Darrin M. Beaupre, Robert K. Bradley, Omar Abdel-Wahab
Summary: Therapy resistance is a major challenge in cancer treatment. Through CRISPR-Cas9 screens, we identified the importance of RNA splicing factors in determining response to BCL2 inhibitor venetoclax in acute myeloid leukemia. Inhibition of splicing kinases CLKs and DYRKs can overcome resistance to BCL2 inhibition by inducing aberrant splicing of key factors.
Article
Multidisciplinary Sciences
Anthony C. Restaino, Austin Walz, Samuel J. Vermeer, Jeffrey Barr, Attila Kovacs, Robin R. Fettig, Daniel W. Vermeer, Hunter Reavis, Caitlin S. Williamson, Christopher T. Lucido, Tuany Eichwald, Dalia K. Omran, Euihye Jung, Lauren E. Schwartz, Maria Bell, DesiRae M. Muirhead, Jody E. Hooper, William C. Spanos, Ronny Drapkin, Sebastien Talbot, Paola D. Vermeer
Summary: The functional role of intratumoral nerves in disease is not well understood. Our study demonstrates that these nerves form functional connections within tumors, with significantly higher electrical activity observed in malignancies compared to benign disease or normal tissues. We also show that pharmacologic silencing of tumoral electrical activity is possible, and animals lacking nociceptor neurons exhibit reduced electrical activity in implanted tumors. Furthermore, the presence of the neuropeptide Substance P and its receptor NK1R within tumors promote cellular proliferation and migration. This study reveals a mechanism by which intratumoral nerves contribute to cancer progression.
Article
Biochemistry & Molecular Biology
Yoshihiro Ishikawa, Arkadiusz Bonna, Douglas B. Gould, Richard W. Farndale
Summary: Mutations in the FKBP14 gene result in kyphoscoliotic Ehlers-Danlos Syndrome (EDS), and FKBP22 selectively binds to collagens III, IV, VI, and X. The binding distribution of FKBP22 along the collagen helix and its correlation with positive peptide charge have been observed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Mengya Zhao, Kenichi Toma, Benyam Kinde, Liang Li, Amit K. Patel, Kong-Yan Wu, Matthew R. Lum, Chengxi Tan, Jody E. Hooper, Arnold R. Kriegstein, Anna La Torre, Yaping Joyce Liao, Derek S. Welsbie, Yang Hu, Ying Han, Xin Duan
Summary: Chronic neurodegeneration and acute injuries lead to neuron losses via diverse processes. We compared retinal ganglion cell (RGC) responses between chronic glaucomatous conditions and the acute injury model. Among major RGC subclasses, aRGCs and intrinsically photosensitive RGCs (ipRGCs) preferentially survive glaucomatous conditions, similar to findings in the retina subject to axotomy. This study reveals the role of Spp1 in mediating neuronal resiliency in glaucoma, as Spp1 overexpression can protect susceptible RGC subclasses.
Article
Rheumatology
Zsuzsanna H. Mcmahan, Subhash Kulkarni, Felipe Andrade, Jamie Perin, Chengxiu Zhang, Jody E. Hooper, Fredrick M. Wigley, Antony Rosen, Pankaj J. Pasricha, Livia Casciola-Rosen
Summary: Gephyrin is identified as a novel autoantigen in the enteric nervous system (ENS) that is associated with constipation in patients with systemic sclerosis (SSc). Anti-gephyrin antibodies are present in 9% of SSc patients and are associated with higher constipation scores and more severe constipation and distention/bloating. Gephyrin is expressed in the ENS, supporting its role in regulating gut motility.
ARTHRITIS & RHEUMATOLOGY
(2023)
Article
Neurosciences
Varun Sagi, Nikitha Kosaraju, Lindsay S. Moore, Jip Y. Mulders, Mehmet Solyali, Xiaojie Ma, Donald P. Regula, Jody E. Hooper, Konstantina M. Stankovic
Summary: This article aims to encourage ongoing study of human temporal bones (HTBs) and outlines the necessary steps to establish a pipeline for collecting and processing HTBs. The article provides details on the design of a tool for collecting specimens, methods to reduce decalcification time, and techniques for immunostaining and drilling, to expedite the processing of HTBs. Collected HTBs can be used for various purposes and contribute to a better understanding of the cellular and molecular basis of otologic disorders.
FRONTIERS IN NEUROSCIENCE
(2023)
Meeting Abstract
Oncology
Yvonne A. Evrard, Michelle Eugeni, Michelle Ahalt-Gottholm, Carrie Bonomi, Suzanne Borgel, Thomas C. Caffrey, John Carter, Ting-Chia Chang, Li Chen, Kevin Cooper, Biswajit Das, Emily Delaney, Kelly Dougherty, Eleonora Duregon, Stephanie Ecker, Joe Geraghty, Marion Gibson, Lauren Hicks, Jenna Hull, Sharon Int Veldt, Shahanawaz Jiwani, Chris A. Karlovich, Jade Loewenstein, Candace Mallow, Chelsea McGlynn, Justine Mills, Tiffanie Miner, Jowaly Schneider, Tia Shearer, Savanna Styers, Shannon Uzelac, Paul Grandgenett, Michael Hollingsworth, Jody E. Hooper, P. Mickey Williams, Melinda Hollingshead, James H. Doroshow