Review
Biochemistry & Molecular Biology
Ana Garcia-Osta, Jinya Dong, Maria Jesus Moreno-Aliaga, Maria Javier Ramirez
Summary: The cell cycle is regulated by factors such as p27(Kip1), which controls different functions in the nucleus and cytoplasm. In Alzheimer's disease, alterations to cell cycle events and increased neurogenesis have been observed, suggesting a role for p27(Kip1) in the disease process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Brian DeVeale, Leqian Liu, Ryan Boileau, Jennifer Swindlehurst-Chan, Bryan Marsh, Jacob W. Freimer, Adam Abate, Robert Blelloch
Summary: This study reveals the cell cycle structure of pluripotent embryonic stem cells and the relationship between G1/S restriction point, gene expression, and cellular differentiation. By genetically manipulating G1/S restriction point regulators miR-302 and P27, the researchers found that they can accelerate or delay the onset of phasic gene expression in mouse embryos. Additionally, loss of miR-302-mediated p21 or p27 suppression expedites embryonic stem cell differentiation, while a mutated Cyclin E blocks it. These findings provide new insights into our understanding of cellular differentiation.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Qun Xie, Ruirui Zhang, Dandan Liu, Jing Yang, Qiang Hu, Chao Shan, Xiaohan Li
Summary: This study investigated the effects of Apigenin and miR-512-3p in melanoma treatment. The results showed that Apigenin inhibited the expression of miR-512-3p and halted cell proliferation in melanoma cells. Furthermore, Apigenin treatment suppressed tumor growth in vivo by decreasing miR-512-3p levels and increasing p27 Kip1 protein levels.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2022)
Review
Oncology
Diana Gulei, Rares Drula, Gabriel Ghiaur, Anca Dana Buzoianu, Yelena Kravtsova-Ivantsiv, Ciprian Tomuleasa, Aaron Ciechanover
Summary: The ubiquitin-proteasome system (UPS) is crucial for protein degradation, and its dysregulation is closely related to malignant pathologies. KPC1, an E3 ubiquitin ligase component, plays a key role in cancer by regulating p27 signaling and the NF-xB pathway. KPC1 maintains the ubiquitination of cytoplasmic p27, influencing cell-cycle progression, and also induces the ubiquitination of p105 to control NF-xB signaling. Therapeutic reinforcement of the KPC1-p50 axis shows promising tumor suppressor activity in multiple malignancies.
Article
Cell Biology
Cheng-Han Tsai, Chun-Yuan Chang, Bing-Ze Lin, Yu-Lou Wu, Meng-Hsiu Wu, Liang-Tin Lin, Wen-Chien Huang, Jonathan D. Holz, Tzong-Jen Sheu, Jhih-Shian Lee, Richard N. Kitsis, Pei-Han Tai, Yi-Jang Lee
Summary: The study found that cofilin-1 plays a crucial role in cell senescence by affecting morphological changes and cell enlargement. It induces cell senescence through the regulation of p27(Kip1), independent of p53 and p16(INK4) expressions. Additionally, cofilin-1 upregulation can also induce the expression of p27(Kip1) by suppressing the TEAD1 transcription factor, which in turn leads to senescence-related phenotypes.
Article
Chemistry, Medicinal
Kun Zhang, Kaizhao Hu, Qian Li, Min Li, Ke Gao, Kecheng Yang, Bing Zhao, Xiao-Jing Shi, Lirong Zhang, Hong-Min Liu
Summary: Skp2 is a component of cullin-RING ligases, and its high expression is associated with aggressive tumor tissues and poor prognosis. In this study, a series of new Skp2 inhibitors were synthesized and their structure-activity relationship was systematically studied. Among them, compound 14i showed potent activity against Skp2 and exhibited effective anticancer effects on PC-3 and MGC-803 cells as well as xenograft mouse models.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Shudong Niu, Kaixin Cheng, Longzhong Jia, Jing Liang, Lu Mu, Yibo Wang, Xuebing Yang, Chen Yang, Yan Zhang, Chao Wang, Lijun Huang, Huarong Wang, Shuang Zhang, Hua Zhang
Summary: This study demonstrated that ovarian granulosa cell tumors (GCTs) originate from mutant granulosa cells (GCs) and identified the upregulation of immune evasion genes Cd24a and Cd47 as a mechanism for the transition of mutant GCs to GCTs. Treatment with the Cd47 inhibitor RRX-001 effectively suppressed GCT growth in vivo.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Oncology
Qing Li, Baishan Jiang, Jiaye Guo, Hong Shao, Isabella S. Del Priore, Qing Chang, Rei Kudo, Zhiqiang Li, Pedram Razavi, Bo Liu, Andrew S. Boghossian, Matthew G. Rees, Melissa M. Ronan, Jennifer A. Roth, Katherine A. Donovan, Marta Palafox, Jorge S. Reis-Filho, Elisa de Stanchina, Eric S. Fischer, Neal Rosen, Violeta Serra, Andrew Koff, John D. Chodera, Nathanael S. Gray, Sarat Chandarlapaty
Summary: This study identifies CDK4/6 kinase activation as a common mechanism in oncogenic signaling-induced proliferation and develops a new strategy for inhibiting CDK4/6 kinases to overcome resistance.
Review
Cell Biology
Dexin Shen, Lingao Ju, Fenfang Zhou, Mengxue Yu, Haoli Ma, Yi Zhang, Tongzu Liu, Yu Xiao, Xinghuan Wang, Kaiyu Qian
Summary: Melatonin, as a potential therapy for prostate cancer, has significant antioxidant and anticancer abilities. Studies have shown that melatonin can inhibit the development of prostate cancer through different pathways, and the synergistic use with other drugs may have better effects.
CELL COMMUNICATION AND SIGNALING
(2021)
Article
Biochemistry & Molecular Biology
Bach D. Nguyen, Brenna L. Stevens, Daniel J. Elson, Darren Finlay, John T. Gamble, Prasad R. Kopparapu, Robyn L. Tanguay, Andrew B. Buermeyer, Nancy I. Kerkvliet, Siva K. Kolluri
Summary: This study provides a detailed characterization of 11-Cl-BBQ as a selective modulator of AhR-regulated transcription with anti-cancer actions. Treatment with 11-Cl-BBQ induces potent and sustained anti-proliferative effects in lung cancer cells by promoting G1 phase cell cycle arrest. RNA-sequencing reveals activation of p53 signaling and suppression of DNA replication pathways by 11-Cl-BBQ in an AhR-dependent manner.
Article
Biochemistry & Molecular Biology
Ji Wang, Zongyu Xiao, Peng Li, Chunwang Wu, Yan Li, Qing Wang, Yanming Chen, Honglong Zhou, Zhi Li, Zhaotao Wang, Qing Lan, Yezhong Wang
Summary: PRMT6, a type I arginine methyltransferase, asymmetrically di-methylates the arginine residues of both histones and non-histones. Increasing evidence indicates that PRMT6 plays a tumor mediator involved in human malignancies. Investigation of PRMT6 expression in glioma tissues demonstrated that PRMT6 is overexpressed, and elevated expression of PRMT6 is negatively correlated with poor prognosis in glioma/GBM patients. Silencing PRMT6 inhibited GBM cell proliferation and induced cell cycle arrest at the G0/G1 phase, while overexpressing PRMT6 had opposite results.
Article
Oncology
Artemis Filippou, Henna Pehkonen, Piia-Riitta Karhemo, Juho Vaananen, Anni I. Nieminen, Juha Klefstrom, Reidar Grenman, Antti A. Makitie, Heikki Joensuu, Outi Monni
Summary: The study revealed that ANO1 plays a crucial role in the oncogenic processes of HNSCC, with its depletion leading to dysregulation of cell cycle and apoptosis pathways, as well as suppression of cell viability. ANO1 may serve as a potential drug target that warrants further evaluation in preclinical in vivo models.
Article
Cell Biology
Zhendong Xiang, Yin Sun, Bosen You, Meng Zhang, Chiping Huang, Junfeng Yu, Xiangyun You, Denglong Wu, Chawnshang Chang
Summary: The study found that Enzalutamide-resistant prostate cancer cells can be suppressed by high doses of the androgen DHT. Targeting the BCL-XL protein can enhance the inhibitory effect of high-dose DHT on cell growth, promoting cell death.
CELL DEATH & DISEASE
(2021)
Article
Multidisciplinary Sciences
Qihong Yu, Jin-Xin Liu, Xichuan Zheng, Xueke Yan, Peng Zhao, Chuanzheng Yin, Wei Li, Zifang Song
Summary: This study reveals the significant role of Sox9 in mediating autophagy-dependent vSMC phenotypic modulation and the development of TA. Inhibition of Sox9 expression can attenuate neointimal formation, providing a potential therapeutic approach for vascular pathologies.
Article
Pathology
Ken Sasai, Kouichi Tabu, Takashi Saito, Yukio Matsuba, Takaomi C. Saido, Shinya Tanaka
Summary: GLI1 is able to transform immortalized human astrocytes, while FOXM1 fails to induce malignant transformation. The downregulation of p27(KIP1) contributes to the malignant features of transformed astrocytes. Models using immortalized/transformed astrocytes are useful for identifying essential changes required for glioma formation.
PATHOLOGY RESEARCH AND PRACTICE
(2021)
Article
Developmental Biology
Laurine Gagniac, Mariam Rusidze, Frederic Boudou, Stephanie Cagnet, Marine Adlanmerini, Pauline Jeannot, Nicolas Gaide, Frank Giton, Arnaud Besson, Ariane Weyl, Pierre Gourdy, Isabelle Raymond-Letron, Jean-Francois Arnal, Cathrin Brisken, Francoise Lenfant
Article
Multidisciplinary Sciences
Gabrielle Sueur, Alison Boutet, Mathilde Gotanegre, Veronique Mansat-De Mas, Arnaud Besson, Stephane Manenti, Sarah Bertoli
SCIENTIFIC REPORTS
(2020)
Article
Oncology
Maelle Cartel, Pierre-Luc Mouchel, Mathilde Gotanegre, Laure David, Sarah Bertoli, Veronique Mansat-De Mas, Arnaud Besson, Jean-Emmanuel Sarry, Stephane Manenti, Christine Didier
Summary: The research demonstrates that inhibition of deubiquitinylase USP7 reduces cell proliferation, blocks DNA replication, and increases cell death in AML. High expression of USP7 is associated with resistance to therapy in AML patients, indicating USP7 as both a marker of resistance and a potential therapeutic target for overcoming treatment resistance.
Review
Cell Biology
Justine Creff, Arnaud Besson
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Anne Prel, Christine Dozier, Jean-Philippe Combier, Serge Plaza, Arnaud Besson
Summary: Some miRNAs are located in long non-coding RNA precursors, which may potentially encode miPEPs. While plant miPEPs enhance the transcription of their own pri-miRNAs, it is not a general rule for human miPEPs to regulate their own miRNAs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Ada Nowosad, Justine Creff, Pauline Jeannot, Raphael Culerrier, Patrice Codogno, Stephane Manenti, Laurent Nguyen, Arnaud Besson
Summary: In response to glucose starvation, p27 promotes autophagy by facilitating autophagosome trafficking along microtubule tracks via maintaining elevated microtubule acetylation through an ATAT1-dependent mechanism.
CELL DEATH & DISEASE
(2021)
Correction
Cell Biology
Ada Nowosad, Pauline Jeannot, Caroline Callot, Justine Creff, Renaud Thierry Perchey, Carine Joffre, Patrice Codogno, Stephane Manenti, Arnaud Besson
NATURE CELL BIOLOGY
(2021)
Article
Medicine, Research & Experimental
Andre Mouraux, Petra Bloms-Funke, Irmgard Boesl, Ombretta Caspani, Sonya C. Chapman, Giulia Di Stefano, Nanna Brix Finnerup, Luis Garcia-Larrea, Marcus Goetz, Anna Kostenko, Bernhard Pelz, Esther Pogatzki-Zahn, Karin Schubart, Alexandre Stouffs, Andrea Truini, Irene Tracey, Inaki F. Troconiz, Johannes Van Niel, Jose Miguel Vela, Katy Vincent, Jan Vollert, Vishvarani Wanigasekera, Matthias Wittayer, Keith G. Phillips, Rolf-Detlef Treede
Summary: IMI2-PainCare-BioPain-RCT3 aims to profile functional biomarkers of drug effects on the nociceptive system and accelerate the future development of analgesics. The study involves various methods including EEG measurements in healthy subjects and medication trials, with concurrent evaluation of drug effects in normal and hyperalgesic conditions. The research hypothesizes that EEG-derived measures can serve as biomarkers of target engagement of analgesic drugs.
Article
Medicine, Research & Experimental
Zahra Nochi, Hossein Pia, Petra Bloms-Funke, Irmgard Boesl, Ombretta Caspani, Sonya C. Chapman, Francesca Fardo, Bernd Genser, Marcus Goetz, Anna V. Kostenko, Caterina Leone, Thomas Li, Andre Mouraux, Bernhard Pelz, Esther Pogatzki-Zahn, Andreas Schilder, Erik Schnetter, Karin Schubart, Alexandre Stouffs, Irene Tracey, Inaki F. Troconiz, Andrea Truini, Johannes Van Niel, Jose Miguel Vela, Katy Vincent, Jan Vollert, Vishvarani Wanigasekera, Matthias Wittayer, Hatice Tankisi, Nanna B. Finnerup, Keith G. Phillips, Rolf-Detlef Treede
Summary: This study aims to identify the effects of drugs on the nociceptive system through nerve excitability testing (NET) and use it as a biomarker for the development of analgesics. The study will evaluate the impact of different medications on large sensory and motor fibers, as well as small sensory fibers, and collect data and blood samples for analysis.
Article
Biochemistry & Molecular Biology
Ada Nowosad, Arnaud Besson
Summary: Lysosomes, initially known for their degradative functions, have emerged as signaling hubs that regulate various cellular processes and play a role in stem cell fate regulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Christine Dozier, Audrey Montigny, Mireia Viladrich, Raphael Culerrier, Jean-Philippe Combier, Arnaud Besson, Serge Plaza
Summary: miRNAs are small regulatory non-coding RNAs generated from pri-miRNAs, with some hosted in lncRNAs containing translatable smORFs. This study demonstrates the involvement of smORFs in regulating pri-miRNAs and miRNAs expression in Human and Drosophila, independent of nucleotide and amino acid sequences.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Franck Talmont, Elodie Mitri, Christine Dozier, Arnaud Besson, Olivier Cuvillier, Anastassia Hatzoglou
Summary: Sphingosine 1-phosphate (S1P), a lipid metabolite, interacts with five high-affinity G protein-coupled receptors (S1P1-5) to regulate cell proliferation, survival, and migration. The role of S1P5 in cell proliferation is limited and inconsistent. This study found that unlike other S1P receptors, S1P5 has an anti-proliferative function and promotes cell immortalization and proliferation by controlling the spatial activation of ERK. These findings provide new insights into the anti-proliferative function of S1P5.
Article
Cell Biology
Justine Creff, Ada Nowosad, Anne Prel, Anne Pizzoccaro, Marion Aguirrebengoa, Nicolas Duquesnes, Caroline Callot, Thomas Jungas, Christine Dozier, Arnaud Besson
Summary: p57Kip2 is a cyclin/CDK inhibitor that regulates intestinal stem cell (ISC) fate and proliferation in a CDK-independent manner. In the absence of p57, there is increased proliferation of intestinal crypts and amplification of transit-amplifying cells and Hopx+ ISCs. RNA sequencing analyses reveal significant gene expression changes in Hopx+ ISCs upon p57 depletion. Furthermore, p57 binds to and inhibits the activity of Ascl2, a transcription factor critical for ISC specification and maintenance, by recruiting a corepressor complex. Hence, p57 plays a key role in maintaining Hopx+ ISC quiescence and repressing the ISC phenotype by inhibiting Ascl2 in a CDK-independent manner during intestinal development.
Article
Biochemical Research Methods
Ada Nowosad, Arnaud Besson
Summary: The protocol presented offers a method to monitor starvation-induced autophagy using a live high-throughput microscopy system without the need for sample preparation. By generating turboGFP-LC3B expressing mouse embryonic fibroblasts, autophagy can be measured over time, and data can be analyzed effectively.
Review
Cell & Tissue Engineering
Justine Creff, Laurent Malaquin, Arnaud Besson
Summary: Recent advances in bioengineering have led to the development of various in vitro models to mimic the complex intestinal epithelium for studying fundamental mechanisms and drug screening. These microfabricated systems provide alternative approaches for understanding intestinal homeostasis and pathologies.
JOURNAL OF TISSUE ENGINEERING
(2021)