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JOURNAL ARTICLE
Haiyan E Liu, Meghah Vuppalapaty, Christian R Hoerner, Colin P Bergstrom, Michael Chiu, Clementine Lemaire, James Che, Amanpreet Kaur, Adam Dimmick, Sean Liu, Thomas J Metzner, Menna Araya, Steve Crouse, Markus Sprenger-Haussels, Martin Schlumpberger, John T Leppert, Siegfried Hauch, Elodie Sollier, Alice C Fan
BACKGROUND: Therapies for metastatic castration-resistant prostate cancer (mCRPC) include targeting the androgen receptor (AR) with androgen receptor inhibitors (ARIs) and prostate-specific membrane antigen (PSMA). Having the ability to detect AR, AR splice variant 7 (AR-V7), or PSMA in circulating tumor cells (CTCs) or circulating exosomal cell-free RNA (cfRNA) could be helpful to guide selection of the appropriate therapy for each individual patient. The Vortex Biosciences VTX-1 system is a label-free CTC isolation system that enables the detection of the expression of multiple genes in both CTCs and exosomal cfRNA from the same blood sample in patients with mCRPC...
April 16, 2024: BMC Cancer
#2
JOURNAL ARTICLE
Chun-Peng Pai, Han Wang, Darcie D Seachrist, Neel Agarwal, Joshua A Adams, Zhenghao Liu, Ruth A Keri, Kaixiang Cao, William P Schiemann, Hung-Ying Kao
The alternative splicing of PML precursor mRNA gives rise to various PML isoforms, yet their expression profile in breast cancer cells remains uncharted. We discovered that PML1 is the most abundant isoform in all breast cancer subtypes, and its expression is associated with unfavorable prognosis in estrogen receptor-positive (ER+) breast cancers. PML depletion reduces cell proliferation, invasion, and stemness, while heterologous PML1 expression augments these processes and fuels tumor growth and resistance to fulvestrant, an FDA-approved drug for ER+ breast cancer, in a mouse model...
April 16, 2024: Cell Death and Differentiation
#3
JOURNAL ARTICLE
Yifei Yang, Guangyao Lv, Ruijuan Xiu, Huijie Yang, Wenyan Wang, Pengfei Yu, Jianzhao Zhang, Liang Ye, Hongbo Wang, Jingwei Tian
The androgen receptor AR antagonists, such as enzalutamide and apalutamide, are efficient therapeutics for the treatment of prostate cancer (PCa). Even though they are effective at first, resistance to both drugs occurs frequently. Resistance is mainly driven by aberrations of the AR signaling pathway including AR gene amplification and the expression of AR splice variants (e.g. AR-V7). This highlights the urgent need for alternative therapeutic strategies. Here, a total of 24 compounds were synthesized and biologically evaluated to disclose compound 20i, exhibiting potent AR antagonistic activities (IC50 = 172...
April 15, 2024: European Journal of Medicinal Chemistry
#4
JOURNAL ARTICLE
Francisco Aya, Pablo Lanuza-Gracia, Abel González-Pérez, Sophie Bonnal, Estefania Mancini, Nuria López-Bigas, Ana Arance, Juan Valcárcel
Resistance to MAPK inhibitors (MAPKi), the main cause of relapse in BRAF-mutant melanoma, is associated with the production of alternative BRAF mRNA isoforms (altBRAFs) in up to 30% of patients receiving BRAF inhibitor monotherapy. These altBRAFs have been described as being generated by alternative pre-mRNA splicing, and splicing modulation has been proposed as a therapeutic strategy to overcome resistance. In contrast, we report that altBRAFs are generated through genomic deletions. Using different in vitro models of altBRAF-mediated melanoma resistance, we demonstrate the production of altBRAFs exclusively from the BRAF V600E allele, correlating with corresponding genomic deletions...
April 9, 2024: Cell Reports
#5
REVIEW
Greater Kayode Oyejobi, Xiaodan Yan, Piotr Sliz, Longfei Wang
Originally discovered in C. elegans , LIN28 is an evolutionarily conserved zinc finger RNA-binding protein (RBP) that post-transcriptionally regulates genes involved in developmental timing, stem cell programming, and oncogenesis. LIN28 acts via two distinct mechanisms. It blocks the biogenesis of the lethal-7 (let-7) microRNA (miRNA) family, and also directly binds messenger RNA (mRNA) targets, such as IGF-2 mRNA, and alters downstream splicing and translation events. This review focuses on the molecular mechanism of LIN28 repression of let-7 and current strategies to overcome this blockade for the purpose of cancer therapy...
March 22, 2024: International Journal of Molecular Sciences
#6
JOURNAL ARTICLE
Shohei Yoshida, Daisuke Kajiwara, Masanao Seki, Manabu Tayama, Yuki Tanaka, Hiroya Mizutani, Ryoto Fujita, Keisuke Yamamura, Shigeo Okajima, Masanori Asai, Kazuhisa Minamiguchi
Second-generation androgen receptor (AR) signaling inhibitors (ARSIs), such as abiraterone and enzalutamide, prolong the life of patients with castration-resistant prostate cancer (CRPC). However, patients receiving ARSIs ultimately develop resistance through various complex mechanisms, including AR mutations, constitutively active AR-splice variants (AR-Vs), and AR overexpression. Here, we characterized a novel AR pure antagonist, TAS3681, which inhibits AR transcriptional activity and downregulates AR-full length (AR-FL) and AR-Vs...
April 10, 2024: Molecular Oncology
#7
JOURNAL ARTICLE
Matheus H Dias, Vladyslava Liudkovska, Jasmine Montenegro Navarro, Lisanne Giebel, Julien Champagne, Chrysa Papagianni, Onno B Bleijerveld, Arno Velds, Reuven Agami, René Bernards, Maciej Cieśla
Perturbation of protein phosphorylation represents an attractive approach to cancer treatment. Besides kinase inhibitors, protein phosphatase inhibitors have been shown to have anti-cancer activity. A prime example is the small molecule LB-100, an inhibitor of protein phosphatases 2A/5 (PP2A/PP5), enzymes that affect cellular physiology. LB-100 has proven effective in pre-clinical models in combination with immunotherapy, but the molecular underpinnings of this synergy remain understood poorly. We report here a sensitivity of the mRNA splicing machinery to phosphorylation changes in response to LB-100 in colorectal adenocarcinoma...
April 10, 2024: EMBO Reports
#8
JOURNAL ARTICLE
Jie Peng, Shuang Gao, Jing-Hu Bi, Juan Shi, Ling Jia, Qi-Fan Pang, Dong-Mei Zhao, Ying Fu, Fei Ye
Mesosulfuron-methyl, an inhibitor of acetolactate synthase (ALS), has been extensively used in wheats. However, it can damage wheat ( Triticum aestivum ) and even lead to crop death. Herbicide safeners selectively shield crops from such damage without compromising weed control. To mitigate the phytotoxicity of mesosulfuron-methyl in crops, several purine derivatives were developed based on active substructure splicing. The synthesized title compounds underwent thorough characterization using infrared spectroscopy, 1 H nuclear magnetic resonance (1 H NMR), 13 C nuclear magnetic resonance (13 C NMR), and high-resolution mass spectrometry...
April 10, 2024: Journal of Agricultural and Food Chemistry
#9
JOURNAL ARTICLE
Seyed M Ghiasi, Piero Marchetti, Lorenzo Piemonti, Jens H Nielsen, Bo T Porse, Thomas Mandrup-Poulsen, Guy A Rutter
INTRODUCTION: Proinflammatory cytokines are implicated in pancreatic ß cell failure in type 1 and type 2 diabetes and are known to stimulate alternative RNA splicing and the expression of nonsense-mediated RNA decay (NMD) components. Here, we investigate whether cytokines regulate NMD activity and identify transcript isoforms targeted in ß cells. METHODS: A luciferase-based NMD reporter transiently expressed in rat INS1(832/13), human-derived EndoC-ßH3, or dispersed human islet cells is used to examine the effect of proinflammatory cytokines (Cyt) on NMD activity...
2024: Frontiers in Endocrinology
#10
JOURNAL ARTICLE
Xiaoyi Huo, Yinna Wang, Zheming Liu, Jia Liu, Hang Zhu, Yong Zhou, Yilong Man, Xiaomao Zhou, Haihao Ma
The slowpoke channel responds to the intracellular calcium concentration and the depolarization of the cell membrane. It plays an important role in maintaining the resting potential and regulating the homeostasis of neurons, but it can also regulate circadian rhythm, sperm capacitation, ethanol tolerance, and other physiological processes in insects. This renders it a potentially useful target for the development of pest control strategies. There are relatively few studies on the slowpoke channels in lepidopteran pests, and their pharmacological properties are still unclear...
March 2024: Pesticide Biochemistry and Physiology
#11
REVIEW
Zhi Xiong Chong, Wan Yong Ho, Swee Keong Yeap
LIM domains kinase 2 (LIMK2) is a 72 kDa protein that regulates actin and cytoskeleton reorganization. Once phosphorylated by its upstream activator (ROCK1), LIMK2 can phosphorylate cofilin to inactivate it. This relieves the levering stress on actin and allows polymerization to occur. Actin rearrangement is essential in regulating cell cycle progression, apoptosis, and migration. Dysregulation of the ROCK1/LIMK2/cofilin pathway has been reported to link to the development of various solid cancers such as breast, lung, and prostate cancer and liquid cancer like leukemia...
April 3, 2024: Life Sciences
#12
JOURNAL ARTICLE
Abu Tayab Moin, Tanjin Barketullah Robin, Rajesh B Patil, Nurul Amin Rani, Anindita Ash Prome, Tahsin Islam Sakif, Mohabbat Hossain, Dil Umme Salma Chowdhury, Shah Samiur Rashid, A K M Moniruzzaman Mollah, Saiful Islam, Mohammad Helal Uddin, Mohammad Khalequzzaman, Tofazzal Islam, Nazneen Naher Islam
Rice blast disease, caused by the fungus Magnaporthe oryzae, poses a severe threat to rice production, particularly in Asia where rice is a staple food. Concerns over fungicide resistance and environmental impact have sparked interest in exploring natural fungicides as potential alternatives. This study aimed to identify highly potent natural fungicides against M. oryzae to combat rice blast disease, using advanced molecular dynamics techniques. Four key proteins (CATALASE PEROXIDASES 2, HYBRID PKS-NRPS SYNTHETASE TAS1, MANGANESE LIPOXYGENASE, and PRE-MRNA-SPLICING FACTOR CEF1) involved in M...
2024: PloS One
#13
JOURNAL ARTICLE
Matthieu Groh, Laurène Fenwarth, Mathilde Labro, Augustin Boudry, Elise Fournier, Mathieu Wemeau, Alice Marceau-Renaut, Rafael Daltro de Oliveira, Julie Abraham, Marly Barry, Philippe Blanche, Quentin Bodard, Thorsten Braun, Safia Chebrek, Matthieu Decamp, Cécile-Audrey Durel, Edouard Forcade, Mathieu Gerfaud-Valentin, Camille Golfier, Clément Gourguechon, Nathalie Grardel, Olivier Kosmider, Nihal Martis, Sarah Melboucy Belkhir, Fatiha Merabet, Adrien Michon, Stéphane Moreau, Cécile Morice, Antoine Néel, Franck E Nicolini, Laurent Pascal, Florence Pasquier, Andrea Pieragostini, Catherine Roche-Lestienne, Philippe Rousselot, Louis Terriou, Anne Thiebaut-Bertrand, Jean-François Viallard, Claude Preudhomme, Jean-Emmanuel Kahn, Guillaume Lefevre, Nicolas Duployez
We investigated using a custom NGS panel of 149 genes the mutational landscape of 64 consecutive adult patients with tyrosine kinase fusion-negative hypereosinophilia (HE)/hypereosinophilic syndrome (HES) harboring features suggestive of myeloid neoplasm. At least one mutation was reported in 50/64 (78%) patients (compared to 8/44 (18%) patients with idiopathic HE/HES/HEUS used as controls; p < .001). Thirty-five patients (54%) had at least one mutation involving the JAK-STAT pathway, including STAT5B (n = 18, among which the hotspot N642H, n = 13), JAK1 (indels in exon 13, n = 5; V658F/L, n = 2), and JAK2 (V617F, n = 6; indels in exon 13, n = 2)...
April 2, 2024: American Journal of Hematology
#14
JOURNAL ARTICLE
Updating mRNA variants of the human RSK4 gene and their expression in different stressed situations.
Zhenwei Qin, Jianglin Yang, Keyin Zhang, Xia Gao, Qianchuan Ran, Yuanhong Xu, Zhi Wang, Didong Lou, Chunhua Huang, Lucas Zellmer, Guangxue Meng, Na Chen, Hong Ma, Zhe Wang, Dezhong Joshua Liao
We determined RNA spectrum of the human RSK4 (hRSK4) gene (also called RPS6KA6) and identified 29 novel mRNA variants derived from alternative splicing, which, plus the NCBI-documented ones and the five we reported previously, totaled 50 hRSK4 RNAs that, by our bioinformatics analyses, encode 35 hRSK4 protein isoforms of 35-762 amino acids. Many of the mRNAs are bicistronic or tricistronic for hRSK4. The NCBI-normalized NM_014496.5 and the protein it encodes are designated herein as the Wt-1 mRNA and protein, respectively, whereas the NM_001330512...
April 15, 2024: Heliyon
#15
Emma Busarello, Giulia Biancon, Fabio Lauria, Zuhairia Ibnat, Christian Ramirez, Gabriele Tomè, Kristin R Aass, Jennifer VanOudenhove, Therese Standal, Gabriella Viero, Stephanie Halene, Toma Tebaldi
UNLABELLED: Single-cell technologies offer a unique opportunity to explore cellular heterogeneity in hematopoiesis, reveal malignant hematopoietic cells with clinically significant features and measure gene signatures linked to pathological pathways. However, reliable identification of cell types is a crucial bottleneck in single-cell analysis. Available databases contain dissimilar nomenclature and non-concurrent marker sets, leading to inconsistent annotations and poor interpretability...
March 12, 2024: bioRxiv
#16
JOURNAL ARTICLE
Liqun Yang, Zhe Gao, Hang Zhao, Zhimei Zhang, Guangyao Song
OBJECTIVE: To explore whether resveratrol can postpone the fibrosis associated with diabetic cardiomyopathy (DCM) by modulating the mitochondrial autophagy response through the AMPK/SIRT1-mediated IRE1α/PINK signaling pathway. METHODS: A DCM mouse model was established using a high-sugar high-fat diet and streptozotocin. Resveratrol was administered to a subset of the DCM mouse models for comparison. Echocardiography, Masson staining, TNUEL assay, and transmission electron microscopy were employed to evaluate the cardiac status, myocardial fibrosis, myocardial cell apoptosis, and morphological changes of myocardial cells and their internal mitochondria in each group of mice...
March 29, 2024: Alternative Therapies in Health and Medicine
#17
REVIEW
Jindu Zhao, Guo-Ying Li, Xian-Ying Lu, Li-Ran Zhu, Qun Gao
Liver cancer remains as the third leading cause of cancer-related death globally as of 2020. Despite the significant progress made in the field of liver cancer treatment, there is still a lack of effective therapies in patients with advanced cancer and the molecular mechanisms underlying liver cancer progression remain largely elusive. N6-methyladenosine (m6 A) modification, as the most prevalent and abundant internal RNA modification in eukaryotic RNAs, plays an essential role in regulating RNA metabolism including RNA splicing, stability, translation, degradation...
2024: Frontiers in Pharmacology
#18
REVIEW
Scott Auerbach, Beana Puka, Upendarrao Golla, Ilyas Chachoua
Secondary acute myeloid leukemia (sAML) is a heterogeneous malignant hematopoietic disease that arises either from an antecedent hematologic disorder (AHD) including myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), aplastic anemia (AA), or as a result of exposure to genotoxic chemotherapeutic agents or radiotherapy (therapy related AML, tAML). sAML is diagnosed when the number of blasts is ≥20% in the bone marrow or peripheral blood, and it is characterized by poor prognosis, resistance to therapy and low overall survival rate...
February 27, 2024: Life
#19
REVIEW
Haidong Liu, Xiao Li, Yin Shi, Zu Ye, Xiangdong Cheng
Protein phosphatases are primarily responsible for dephosphorylation modification within signal transduction pathways. Phosphatase of regenerating liver-3 (PRL-3) is a dual-specific phosphatase implicated in cancer pathogenesis. Understanding PRL-3's intricate functions and developing targeted therapies is crucial for advancing cancer treatment. This review highlights its regulatory mechanisms, expression patterns, and multifaceted roles in cancer progression. PRL-3's involvement in proliferation, migration, invasion, metastasis, angiogenesis, and drug resistance is discussed...
March 12, 2024: Biomolecules
#20
JOURNAL ARTICLE
So Young Ham, Min Ju Pyo, Moonkyung Kang, Yeon-Soo Kim, Dong Hun Lee, Jin Ho Chung, Seung-Taek Lee
Heat shock protein 47 (HSP47), also known as SERPINH1 , functions as a collagen-specific molecular chaperone protein essential for the formation and stabilization of the collagen triple helix. Here, we delved into the regulatory pathways governed by HSP47, shedding light on collagen homeostasis. Our investigation revealed a significant reduction in HSP47 mRNA levels in the skin tissue of older mice as compared to their younger counterparts. The augmented expression of HSP47 employing lentivirus infection in fibroblasts resulted in an increased secretion of type I collagen...
March 17, 2024: Cells
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