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Gergely Rona, Bearach Miwatani-Minter, Qingyue Zhang, Hailey V Goldberg, Marc A Kerzhnerman, Jesse B Howard, Daniele Simoneschi, Ethan Lane, John W Hobbs, Elizabeth Sassani, Andrew A Wang, Sarah Keegan, Daniel J Laverty, Cortt G Piett, Lorinc S Pongor, Miranda Li Xu, Joshua Andrade, Anish Thomas, Piotr Sicinski, Manor Askenazi, Beatrix Ueberheide, David Fenyö, Zachary D Nagel, Michele Pagano
UNLABELLED: The large majority of oxidative DNA lesions occurring in the G1 phase of the cell cycle are repaired by base excision repair (BER) rather than mismatch repair (MMR) to avoid long resections that can lead to genomic instability and cell death. However, the molecular mechanisms dictating pathway choice between MMR and BER have remained unknown. Here, we show that, during G1, D-type cyclins are recruited to sites of oxidative DNA damage in a PCNA- and p21-dependent manner. D-type cyclins shield p21 from its two ubiquitin ligases CRL1 SKP2 and CRL4 CDT2 in a CDK4/6-independent manner...
January 13, 2024: bioRxiv
#22
JOURNAL ARTICLE
Taichi Ito, Atsushi Saito, Yasunao Kamikawa, Nayuta Nakazawa, Kazunori Imaizumi
Breast cancer ranks first in incidence and fifth in cancer-related deaths among all types of cancer globally. Among breast cancer, triple negative breast cancer (TNBC) has few known therapeutic targets and a poor prognosis. Therefore, new therapeutic targets and strategies against TNBC are required. We found that androgen-induced basic leucine zipper (AIbZIP) [also known as cyclic AMP-responsive element-binding protein 3-like protein 4 (CREB3L4)], which is encoded by Creb3l4, is highly upregulated in a particular subtype of TNBC, luminal androgen receptor (LAR) subtype...
January 18, 2024: Molecular Cancer Research: MCR
#23
REVIEW
Tianyang Feng, Ping Wang, Xiling Zhang
The ubiquitin-proteasome system (UPS) is a multi-step process that serves as the primary pathway for protein degradation within cells. UPS activity also plays a crucial role in regulating various life processes, including the cell cycle, signal transduction, DNA repair, and others. The F-box protein Skp2, a crucial member of the UPS, plays a central role in the development of various diseases. Skp2 controls cancer cell growth and drug resistance by ubiquitinating modifications to a variety of proteins. This review emphasizes the multifaceted role of Skp2 in a wide range of cancers and the mechanisms involved, highlighting the potential of Skp2 as a therapeutic target in cancer...
January 4, 2024: Life Sciences
#24
JOURNAL ARTICLE
Zheng-Yan Yang, Yi-Wei Zhao, Jing-Rui Xue, Ran Guo, Zhi Zhao, Han-Di Liu, Zhi-Guang Ren, Ming Shi
BACKGROUND: Trastuzumab constitutes the fundamental component of initial therapy for patients with advanced human epidermal growth factor receptor 2 (HER-2)-positive gastric cancer (GC). However, the efficacy of this treatment is hindered by substantial challenges associated with both primary and acquired drug resistance. While S-phase kinase associated protein 2 (Skp2) overexpression has been implicated in the malignant progression of GC, its role in regulating trastuzumab resistance in this context remains uncertain...
December 7, 2023: World Journal of Gastroenterology: WJG
#25
REVIEW
Yan Lin, Xiaofeng Jin
Genomic instability is an essential hallmark of cancer, and cellular DNA damage response (DDR) defects drive tumorigenesis by disrupting genomic stability. Several studies have identified abnormalities in DDR-associated genes, and a dysfunctional ubiquitin-proteasome system (UPS) is the most common molecular event in metastatic castration-resistant prostate cancer (PCa). For example, mutations in Speckle-type BTB/POZ protein-Ser119 result in DDR downstream target activation deficiency. Skp2 excessive upregulation inhibits homologous recombination repair and promotes cell growth and migration...
January 2024: Experimental and Therapeutic Medicine
#26
JOURNAL ARTICLE
Di Wang, Xue Zhao, Shuang Li, Haixian Guo, Shaonan Li, Dan Yu
BACKGROUND: LncRNA SRY-box transcription factor 2 overlapping transcript (SOX2-OT) is linked to multiple cancers, but its specific role and mechanism in head and neck squamous cell carcinoma (HNSCC) remain poorly understood. METHODS: We harnessed clinical data and HNSCC transcriptome profiles from UCSC Xena, TCGA, and GEO databases. Employing various algorithms, we assessed the correlation between SOX2-OT expression and the HNSCC immune microenvironment. Differential expression analysis identified immune-enriched miRNAs (DEmiRNAs) and mRNAs (DEmRNAs)...
December 16, 2023: Cellular Signalling
#27
JOURNAL ARTICLE
Asmaa Ibrahim, Michael S Toss, Mansour Alsaleem, Shorouk Makhlouf, Nehal Atallah, Andrew R Green, Emad A Rakha
The use of proliferation markers provides valuable information about the rate of tumor growth, which can guide treatment decisions. However, there is still a lack of consensus regarding the optimal molecular markers or tests to use in clinical practice. Integrating gene expression data with clinical and histopathologic parameters enhances our understanding of disease processes, facilitates the identification of precise prognostic predictors, and supports the development of effective therapeutic strategies. The purpose of this study was to apply an integrated approach that combines morphologic, clinical, and bioinformatic data to reveal effective regulators of proliferation...
December 15, 2023: Modern Pathology
#28
JOURNAL ARTICLE
Silvia Pomella, Matteo Cassandri, Lucrezia D'Archivio, Antonella Porrazzo, Cristina Cossetti, Doris Phelps, Clara Perrone, Michele Pezzella, Antonella Cardinale, Marco Wachtel, Sara Aloisi, David Milewski, Marta Colletti, Prethish Sreenivas, Zoë S Walters, Giovanni Barillari, Angela Di Giannatale, Giuseppe Maria Milano, Cristiano De Stefanis, Rita Alaggio, Sonia Rodriguez-Rodriguez, Nadia Carlesso, Christopher R Vakoc, Enrico Velardi, Beat W Schafer, Ernesto Guccione, Susanne A Gatz, Ajla Wasti, Marielle Yohe, Myron Ignatius, Concetta Quintarelli, Janet Shipley, Lucio Miele, Javed Khan, Peter J Houghton, Francesco Marampon, Berkley E Gryder, Biagio De Angelis, Franco Locatelli, Rossella Rota
Rhabdomyosarcomas (RMS) are pediatric mesenchymal-derived malignancies encompassing PAX3/7-FOXO1 Fusion Positive (FP)-RMS, and Fusion Negative (FN)-RMS with frequent RAS pathway mutations. RMS express the master myogenic transcription factor MYOD that, whilst essential for survival, cannot support differentiation. Here we discover SKP2, an oncogenic E3-ubiquitin ligase, as a critical pro-tumorigenic driver in FN-RMS. We show that SKP2 is overexpressed in RMS through the binding of MYOD to an intronic enhancer...
December 15, 2023: Nature Communications
#29
JOURNAL ARTICLE
Rashmi Mishra, Steven Blinka, Andrew C Hsieh
Prolonged treatment with androgen deprivation therapy (ADT) inevitably leads to castration-resistant prostate cancer (CRPC). Development of novel androgen-targeting agents and chemo/radiotherapies has resulted in improved survival. However, metastatic CRPC remains incurable. New therapeutics are greatly needed, and exploration of novel pathways such as the mechanisms underlying prostate cancer cell proliferation could potentially augment the natural course of CRPC. In the latest issue of Cancer Research, Rawat and colleagues delved deeply into the mechanistic role of citron kinase (CIT) in orchestrating prostate cancer proliferation and revealed its catalytic activity as a druggable target for treatment-resistant prostate cancer...
December 15, 2023: Cancer Research
#30
EDITORIAL
Ying Wang, Jack L Arbiser
No abstract text is available yet for this article.
November 30, 2023: British Journal of Dermatology
#31
JOURNAL ARTICLE
Shunsuke Hanaki, Makoto Habara, Yuki Sato, Haruki Tomiyasu, Yosei Miki, Shusaku Shibutani, Midori Shimada
The transcription factor NFAT plays key roles in multiple biological activities, such as immune responses, tissue development, and malignant transformation. NFAT is dephosphorylated by calcineurin, which is activated by intracellular calcium levels, and translocated into the nucleus, resulting in transcriptional activation. Calcineurin dephosphorylates various target proteins and regulates their functions. However, the regulation of NFAT degradation is largely unknown, and it is unclear whether calcineurin contributes to the stability of NFAT...
November 29, 2023: Journal of Biochemistry
#32
JOURNAL ARTICLE
Lisa de Las Fuentes, Karen L Schwander, Michael R Brown, Amy R Bentley, Thomas W Winkler, Yun Ju Sung, Patricia B Munroe, Clint L Miller, Hugo Aschard, Stella Aslibekyan, Traci M Bartz, Lawrence F Bielak, Jin Fang Chai, Ching-Yu Cheng, Rajkumar Dorajoo, Mary F Feitosa, Xiuqing Guo, Fernando P Hartwig, Andrea Horimoto, Ivana Kolčić, Elise Lim, Yongmei Liu, Alisa K Manning, Jonathan Marten, Solomon K Musani, Raymond Noordam, Sandosh Padmanabhan, Tuomo Rankinen, Melissa A Richard, Paul M Ridker, Albert V Smith, Dina Vojinovic, Alan B Zonderman, Maris Alver, Mathilde Boissel, Kaare Christensen, Barry I Freedman, Chuan Gao, Franco Giulianini, Sarah E Harris, Meian He, Fang-Chi Hsu, Brigitte Kühnel, Federica Laguzzi, Xiaoyin Li, Leo-Pekka Lyytikäinen, Ilja M Nolte, Alaitz Poveda, Rainer Rauramaa, Muhammad Riaz, Antonietta Robino, Tamar Sofer, Fumihiko Takeuchi, Bamidele O Tayo, Peter J van der Most, Niek Verweij, Erin B Ware, Stefan Weiss, Wanqing Wen, Lisa R Yanek, Yiqiang Zhan, Najaf Amin, Dan E Arking, Christie Ballantyne, Eric Boerwinkle, Jennifer A Brody, Ulrich Broeckel, Archie Campbell, Mickaël Canouil, Xiaoran Chai, Yii-Der Ida Chen, Xu Chen, Kumaraswamy Naidu Chitrala, Maria Pina Concas, Ulf de Faire, Renée de Mutsert, H Janaka de Silva, Paul S de Vries, Ahn Do, Jessica D Faul, Virginia Fisher, James S Floyd, Terrence Forrester, Yechiel Friedlander, Giorgia Girotto, C Charles Gu, Göran Hallmans, Sami Heikkinen, Chew-Kiat Heng, Georg Homuth, Steven Hunt, M Arfan Ikram, David R Jacobs, Maryam Kavousi, Chiea Chuen Khor, Tuomas O Kilpeläinen, Woon-Puay Koh, Pirjo Komulainen, Carl D Langefeld, Jingjing Liang, Kiang Liu, Jianjun Liu, Kurt Lohman, Reedik Mägi, Ani W Manichaikul, Colin A McKenzie, Thomas Meitinger, Yuri Milaneschi, Matthias Nauck, Christopher P Nelson, Jeffrey R O'Connell, Nicholette D Palmer, Alexandre C Pereira, Thomas Perls, Annette Peters, Ozren Polašek, Olli T Raitakari, Kenneth Rice, Treva K Rice, Stephen S Rich, Charumathi Sabanayagam, Pamela J Schreiner, Xiao-Ou Shu, Stephen Sidney, Mario Sims, Jennifer A Smith, John M Starr, Konstantin Strauch, E Shyong Tai, Kent D Taylor, Michael Y Tsai, André G Uitterlinden, Diana van Heemst, Melanie Waldenberger, Ya-Xing Wang, Wen-Bin Wei, Gregory Wilson, Deng Xuan, Jie Yao, Caizheng Yu, Jian-Min Yuan, Wei Zhao, Diane M Becker, Amélie Bonnefond, Donald W Bowden, Richard S Cooper, Ian J Deary, Jasmin Divers, Tõnu Esko, Paul W Franks, Philippe Froguel, Christian Gieger, Jost B Jonas, Norihiro Kato, Timo A Lakka, Karin Leander, Terho Lehtimäki, Patrik K E Magnusson, Kari E North, Ioanna Ntalla, Brenda Penninx, Nilesh J Samani, Harold Snieder, Beatrice Spedicati, Pim van der Harst, Henry Völzke, Lynne E Wagenknecht, David R Weir, Mary K Wojczynski, Tangchun Wu, Wei Zheng, Xiaofeng Zhu, Claude Bouchard, Daniel I Chasman, Michele K Evans, Ervin R Fox, Vilmundur Gudnason, Caroline Hayward, Bernardo L Horta, Sharon L R Kardia, Jose Eduardo Krieger, Dennis O Mook-Kanamori, Patricia A Peyser, Michael M Province, Bruce M Psaty, Igor Rudan, Xueling Sim, Blair H Smith, Rob M van Dam, Cornelia M van Duijn, Tien Yin Wong, Donna K Arnett, Dabeeru C Rao, James Gauderman, Ching-Ti Liu, Alanna C Morrison, Jerome I Rotter, Myriam Fornage
Introduction: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes. Methods: A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational attainment variables: "Some College" (yes/no, for any education beyond high school) and "Graduated College" (yes/no, for completing a 4-year college degree)...
2023: Frontiers in Genetics
#33
JOURNAL ARTICLE
Tomoyuki Kawaguchi, Koichi Okamoto, Shota Fujimoto, Masahiro Bando, Hironori Wada, Hiroshi Miyamoto, Yasushi Sato, Naoki Muguruma, Katsuhisa Horimoto, Tetsuji Takayama
BACKGROUND: Although the serrated-neoplasia pathway reportedly accounts for 15-30% of colorectal cancer (CRC), no studies on chemoprevention of sessile serrated lesions (SSLs) have been reported. We searched for effective compounds comprehensively from a large series of compounds by employing Connectivity Map (CMAP) analysis of SSL-specific gene expression profiles coupled with in vitro screening using SSL patient-derived organoids (PDOs), and validated their efficacy using a xenograft mouse model of SSL...
November 22, 2023: Journal of Gastroenterology
#34
JOURNAL ARTICLE
Gege Li, Changlong Zhou, Lu Wang, Yalong Zheng, Bo Zhou, Guoyan Li, Zhongyu Ma, Peng Sun, Yuantao Deng, Li Su, Junling Wang, Hongmei Cui
Melanoma is an aggressive malignant tumor with a poor prognosis. Vemurafenib (PLX4032, vem) is applied to specifically treat BRAF V600E-mutated melanoma patients. However, prolonged usage of vem makes patients resistant to the drug and finally leads to clinical failure. We previously tested the combination regimen of tubulin inhibitor VERU-111 with vem, as well as USP14 selective inhibitor b-AP15 in combination with vem, both of which have showed profound therapeutic effects in overcoming vem resistance in vitro and in vivo...
November 20, 2023: Pigment Cell & Melanoma Research
#35
REVIEW
Pengyu Zhang, Wendi Liu, Yuan Wang
Tanshinone is a lipophilic compound that is present in traditional Chinese medicine and is derived from the roots of Salvia miltiorrhiza (Danshen). It has been proven to be highly effective in combating tumors in various parts of the body, including liver carcinoma, gastric cancer, ovarian cancer, cervix carcinoma, breast cancer, colon cancer, and prostate cancer. Tanshinone can efficiently prevent the reproduction of cancerous cells, induce cell death, and inhibit the spread of cancerous cells, which are mainly involved in the PI3K/Akt signaling pathway, NF-κB pathway, Bcl-2 family, Caspase cascades, MicroRNA, MAPK signaling pathway, p21, STAT3 pathway, miR30b-P53-PTPN11/SHP2 axis, β-catenin, and Skp2...
2023: Frontiers in Pharmacology
#36
JOURNAL ARTICLE
Huan Wang, Ziye Liu, Dawei Niu, Haobo Li, Yaguang Han, Jinhui Peng, Qirong Qian
BACKGROUND: Antiepileptic drugs (AEDs) harm bone health and are significantly associated with osteoporosis development. In this study, we aimed to explore the mechanisms involved in carbamazepine (CBZ) and microRNA (miR)-20a-5p/ubiquitin-specific peptidase 10 (USP10)/S-phase kinase-associated protein 2 (SKP2) axis in osteoporosis. METHODS: Human bone marrow mesenchymal stem cells (BMSCs) were treated with different concentrations of CBZ. Knocking down or overexpressing miR-20a-5p, USP10, and SKP2 cell lines were constructed...
November 1, 2023: Journal of Orthopaedic Surgery and Research
#37
JOURNAL ARTICLE
Junhe Shi, Trevor R Leonardo, Chen Han, Hiba I Bangash, Dandan Chen, Harsh M Trivedi, Lin Chen
High glucose inhibits oral keratinocyte proliferation. Diabetes can lead to delayed oral wound healing and periodontal disease. L-Arginine, one of the most versatile amino acids, plays an important role in wound healing, organ maturation, and development. In this study, L-Arginine was found to enhance oral keratinocyte proliferation under high-glucose conditions. RNA sequencing analysis discovered a significant number of genes differentially upregulated following L-Arginine treatment under high-glucose conditions...
October 10, 2023: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
#38
JOURNAL ARTICLE
Shilpa Kuttikrishnan, Fareed Ahmad, Jericha M Mateo, Kirti S Prabhu, Tamam El-Elimat, Nicholas H Oberlies, Cedric J Pearce, Ammira S Alshabeeb Akil, Ajaz A Bhat, Feras Q Alali, Shahab Uddin
Multiple myeloma (MM) is a hematologic malignancy associated with malignant plasma cell proliferation in the bone marrow. Despite the available treatments, drug resistance and adverse side effects pose significant challenges, underscoring the need for alternative therapeutic strategies. Natural products, like the fungal metabolite neosetophomone B (NSP-B), have emerged as potential therapeutic agents due to their bioactive properties. Our study investigated NSP-B's antitumor effects on MM cell lines (U266 and RPMI8226) and the involved molecular mechanisms...
October 26, 2023: Cell Biology International
#39
JOURNAL ARTICLE
Alexander Ferrena, Jichuan Wang, Ranxin Zhang, Burcu Karadal-Ferrena, Waleed Al-Hardan, Swapnil Singh, Hasibagan Borjihan, Edward L Schwartz, Hongling Zhao, Maja H Oktay, Rui Yang, David S Geller, Bang H Hoang, Deyou Zheng
Osteosarcoma (OS) is an aggressive bone malignancy with a poor prognosis. One putative proto-oncogene in OS is SKP2, encoding a substrate recognition factor of the SCF E3 ubiquitin ligase. We previously demonstrated that SKP2 knockout in murine OS improved survival and delayed tumorigenesis. Here we performed RNA-sequencing (RNA-seq) on tumors from a transgenic OS mouse model with conditional Trp53 and Rb1 knockouts in the osteoblast lineage ("DKO": Osx1-Cre;Rb1lox/lox;p53lox/lox) and a triple-knockout model with additional Skp2 germline knockout ("TKO": Osx1-Cre;Rb1lox/lox;p53lox/lox;SKP2-/-), followed by qPCR and immunohistochemistry validation...
October 24, 2023: Molecular Cancer Therapeutics
#40
JOURNAL ARTICLE
Sojin Kim, Sungsin Jo, Sun Ha Paek, Sang Soo Kang, Heekyoung Chung
BACKGROUND: Human gliomas are aggressive brain tumors characterized by uncontrolled cell proliferation. Differential expression of Polycomb repressive complex 2 (PRC2) has been reported in various subtypes of glioma. However, the role of PRC2 in uncontrolled growth in glioma and its underlying molecular mechanisms remain to be elucidated. OBJECTIVE: We aimed to investigate the functional role of PRC2 in human glioblastoma cell growth by silencing SUZ12, the non-catalytic core component of PRC2...
October 19, 2023: Genes & Genomics
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