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Dan Wang, Xing Xu, Yue Wu, Yong Lin, Minhui Gao, Peili Hu, Dongjian Chen, Xu Lu, Zhuo Chen, Hui Wang, Chao Huang
This study was designed to examine the potency of SMIP004, an inhibitor of S-phase kinase-associated protein 2 (Skp2), to exert antidepressant-like properties in mouse models following acute or chronic administration to C57BL6/J mice. To this end, the tail suspension test (TST), forced swim test (FST), and sucrose preference test (SPT) were utilized and the antidepressant-like activity of SMIP004 at different concentrations or time points in mice with or without chronic unpredictable stress (CUS) treatment were evaluated...
November 28, 2018: European Journal of Pharmacology
Almudena Chaves-Pérez, Sebastian Thompson, Nabil Djouder
Almost 15 years ago, the URI prefoldin-like complex was discovered by Krek and colleagues in immunoprecipitation experiments conducted in mammalian cells with the aim of identifying new binding partners of the E3 ubiquitin-protein ligase S-phase kinase-associated protein 2 (SKP2) (Gstaiger et al. Science 302(5648):1208-1212, 2003). The URI prefoldin-like complex is a heterohexameric chaperone complex comprising two α and four β subunits (α2β4). The α subunits are URI and STAP1, while the β subunits are PFDN2, PFDN6, and PFDN4r, one of which is probably present in duplicate...
2018: Advances in Experimental Medicine and Biology
Yi-Chun Tsai, Po-Lin Kuo, Mei-Chuan Kuo, Wei-Wen Hung, Ling-Yu Wu, Wei-An Chang, Ping-Hsun Wu, Su-Chu Lee, Hung-Chun Chen, Ya-Ling Hsu
Diabetic nephropathy (DN) is the major cause of end stage renal disease. Proximal tubular epithelial cell (PTEC) injury occurs early in diabetic kidney, and it is correlated with consequent renal failure. Cellular senescence participates in the pathophysiology of DN, but its role remains unclear. We conducted a cross-disciplinary study, including human, in vivo, and in vitro studies, to explore the novel molecular mechanisms of PTEC senescence in DN. We found that HG induced cell senescence in PTECs, supported by enhanced β-galactosidase staining, p53 and p27 expression, and reduced cyclin E levels...
November 22, 2018: Journal of Clinical Medicine
Xiaochen Wang, Shizhen Zhang, Tao Zhang, Jinlan Shan
INTRODUCTION: F-box proteins are the substrate-recognizing subunits of SKP1-cullin1-F-box protein (SCF) E3 ligase complexes that play pivotal roles in multiple cellular processes, including cell proliferation, apoptosis, angiogenesis, invasion and metastasis. Dysregulation of F-box proteins may lead to an unbalanced proteolysis of numerous protein substrates, contributing to progression of human malignancies. However, the prognostic values of F-box members, especially at mRNA levels, in breast cancer are elusive...
October 19, 2018: Bioscience Reports
Abdul Q Khan, Kodappully S Siveen, Kirti S Prabhu, Shilpa Kuttikrishnan, Sabah Akhtar, Abdullah Shaar, Afsheen Raza, Fatima Mraiche, Said Dermime, Shahab Uddin
S-phase kinase-associated protein2 (Skp2), a proto-oncoprotein, plays an important role in development and progression of human malignancies. Skp2 is frequently overexpressed in many human malignancies. It targets cell cycle progression through ubiquitin mediated degradation of G1-checkpoint CDK inhibitors-p21 (CDKN1A) and p27 (CDKN1B). We investigated the role of Skp2 and its ubiquitin-proteasome pathway in head and neck squamous cell carcinoma (HNSCC) using a panel of cell lines with and without human papillomavirus (HPV+ , HPV- )...
2018: Frontiers in Oncology
Yu-Feng Tian, Hui-Ching Wang, Chi-Wen Luo, Wen-Chun Hung, Yu-Han Lin, Tzu-Yi Chen, Chien-Feng Li, Chen-Yi Lin, Mei-Ren Pan
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease, which is characterized by its high invasiveness, rapid progression, and profound resistance to therapy. Gemcitabine is the first-line treatment option for pancreatic cancer patients, but the overall survival is quite low. Therefore, it is an urgent issue to identify new molecules for improved therapies, with better efficacy and less toxicity. Our previous data indicated that Euchromatic histone-lysine N-methyltransferase 2 (EHMT2) functions as a therapeutic target to override GEM resistance and promote metastasis in the treatment of pancreatic cancer...
2018: American Journal of Cancer Research
Yi-Ting Chen, Yu-Chia Su, John T Kung
BCR engagement leads to activation and clonal expansion of B cells. The I-A12% mutant mouse possesses a branch site point mutation in the H2-Aa gene that causes highly reduced I-Aa protein expression. As I-A is a heterodimer made up of I-Aa and I-Ab, reduced I-Aa results not only in reduced surface I-A expression but also in an excess of unpaired I-Ab. B cells that develop in I-A12% mice proliferated in response to LPS stimulation but failed to do so upon BCR stimulation. Developing I-A12% B cells were engaged in unfolded protein response due to an excess of unpaired I-Ab...
October 10, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Leimarembi Devi Naorem, Mathavan Muthaiyan, Amouda Venkatesan
Triple-negative breast cancer (TNBC) has attracted more attention compared with other breast cancer subtypes due to its aggressive nature, poor prognosis, and chemotherapy remains the mainstay of treatment with no other approved targeted therapy. Therefore, the study aimed to discover more promising therapeutic targets and investigating new insights of biological mechanism of TNBC. Six microarray data sets consisting of 463 non-TNBC and 405 TNBC samples were mined from Gene Expression Omnibus. The data sets were integrated by meta-analysis and identified 1075 differentially expressed genes...
October 9, 2018: Journal of Cellular Biochemistry
Ting La, Guang Zhi Liu, Margaret Farrelly, Nicole Cole, Yu Chen Feng, Yuan Yuan Zhang, Simonne K Sherwin, Hamed Yari, Hessam Tabatabaee, Xu Guang Yan, Su Tang Guo, Tao Liu, Rick F Thorne, Lei Jin, Xu Dong Zhang
Cancer cells in quiescence (G0 phase) are resistant to death, and re-entry of quiescent cancer cells into the cell cycle plays an important role in cancer recurrence. Here we show that two p53-responsive microRNAs (miRNAs) utilize distinct but complementary mechanisms to promote cancer cell quiescence by facilitating stabilization of p27. Purified quiescent B16 mouse melanoma cells expressed higher levels of miRNA-27b-3p and miRNA-455-3p relative to their proliferating counterparts. Induction of quiescence resulted in increased levels of these miRNAs in diverse types of human cancer cell lines...
October 9, 2018: Cancer Research
Jun Zhao, Jieying Xu, Wangshen Wang, Han Zhao, Hongbin Liu, Xiaojing Liu, Jiansheng Liu, Yun Sun, Andrea Dunaif, Yanzhi Du, Zi-Jiang Chen
BACKGROUND: Disordered folliculogenesis is a key feature of polycystic ovary syndrome (PCOS), but the underlying molecular mechanism remains unclear. METHODS: Long non-coding RNA (lncRNA) expression in luteinized granulosa cells (hLGCs) derived from women with and without PCOS were analyzed using microarray and qRT-PCR. Immortalized human granulosa cell lines were cultured for proliferation assays after transfection with the LINC-01572:28 over-expression vector in the presence or absence of p27 siRNA...
October 2018: EBioMedicine
Woong Sub Byun, Minkyung Jin, Jinha Yu, Won Kyung Kim, Jayoung Song, Hwa-Jin Chung, Lak Shin Jeong, Sang Kook Lee
Prostate cancer (PC) is the most common disease in men over age 50, and its prevalence rate has been gradually increasing since 1980. Taxane-derived anticancer agents are the primary agents used to treat metastatic prostate cancer patients; however, the side effects and acquired drug resistance limit the success of these therapies. Because there is no specific treatment for paclitaxel-resistant prostate cancer, it is necessary to develop new targets and therapeutic strategies to overcome the acquired resistance...
October 5, 2018: Biochemical Pharmacology
Junhaohui Huo, Xi Chen, Haohao Zhang, Yiming Hu, Yuhang Jiang, Sanhong Liu, Xiaoren Zhang
Bcl-3 is an established oncogene in diverse malignant tumors. In this study, we investigated a dual role of Bcl-3 in BL1-subtype triple-negative breast cancer (TNBC). The BL1-subtype TNBC is featured by increasing cell cycle gene expression and the highest sensitivity to chemotherapy among all subtypes. Bcl-3 is associated with a better prognosis in BL1 patients. Bcl-3 knockdown in BL1 cell MDA-MB-468 induces the inhibition of cell proliferation and the G1/S transition arrest by promoting p27 and reducing the expressions of c-Myc and skp2 at mRNA and protein levels...
November 1, 2018: Acta Biochimica et Biophysica Sinica
Yidan Zhang, Yoav S Zvi, Brian Batko, Nikolas Zaphiros, Edmond F O'Donnell, Jichuan Wang, Kenji Sato, Rui Yang, David S Geller, Pratistha Koirala, Wendong Zhang, Xiuquan Du, Sajida Piperdi, Yang Liu, Deyou Zheng, Michael Roth, Jonathan Gill, Jinghang Zhang, Tingting Ren, Richard Gorlick, Xiaolin Zi, Bang H Hoang
Osteosarcoma (OS), the most common primary cancer of bone, exhibits a high propensity for local invasion and distant metastasis. This study sought to elucidate the role of S phase kinase-associated protein (Skp2) in osteosarcoma invasion and metastasis and to explore flavokawain A (FKA), a natural chalcone from kava extract, as a potential Skp2 targeting agent for preventing osteosarcoma progression. Skp2 was found to be overexpressed in multiple osteosarcoma cell lines, including 5 standard and 8 primary patient-derived cell lines...
September 24, 2018: Scientific Reports
He Shen, Nuo Yang, Alexander Truskinovsky, Yanmin Chen, Ashley L Mussell, Norma J Nowak, Lester Kobzik, Costa Frangou, Jianmin Zhang
Deregulated expression of the transcriptional coactivator with PDZ-binding motif (WWTR1/TAZ) is a common feature of basal-like breast cancer (BLBC). Yet, how oncogenic TAZ regulates cell-cycle progression and proliferation in breast cancer remains poorly understood, and whether TAZ is required for tumor maintenance has not been established. Here, using an integrative oncogenomic approach, TAZ-dependent cellular programs essential for tumor growth and progression were identified. Significantly, TAZ-driven tumor cells required sustained TAZ expression, given that its withdrawal impaired both genesis and maintenance of solid tumors...
September 20, 2018: Molecular Cancer Research: MCR
J G C Peeters, L W Picavet, S G J M Coenen, M Mauthe, S J Vervoort, E Mocholi, C de Heus, J Klumperman, S J Vastert, F Reggiori, P J Coffer, M Mokry, J van Loosdregt
Macroautophagy (hereafter autophagy) is a lysosomal degradation pathway critical for maintaining cellular homeostasis and viability, and is predominantly regarded as a rapid and dynamic cytoplasmic process. To increase our understanding of the transcriptional and epigenetic events associated with autophagy, we performed extensive genome-wide transcriptomic and epigenomic profiling after nutrient deprivation in human autophagy-proficient and autophagy-deficient cells. We observed that nutrient deprivation leads to the transcriptional induction of numerous autophagy-associated genes...
September 11, 2018: Autophagy
Kaize Zhong, Fan Yang, Qiuying Han, Jing Chen, Jun Wang
High expression of S-phase kinase associated protein 2 (Skp2) is associated with numerous clinicopathological parameters, including histology, lymph node metastasis, smoking status, differentiation and Tumor-Node-Metastasis stage in non-small cell lung cancer (NSCLC). Skp2 protein is overexpressed in lung squamous cell carcinoma (LUSC), compared with lung adenocarcinoma (LUAD), whilst the clinicopathological and prognostic implications in LUAD or LUSC remain unclear. A larger study is required to assess the differences in Skp2 expression between these NSCLC types...
September 2018: Oncology Letters
Lea Lough, Dan Sherman, Eric Ni, Lauren M Young, Bing Hao, Timothy Cardozo
Skp2 is a member of the F-box family of proteins that serve as substrate-specific adaptors in Skp1-CUL1-ROC1-F-box (SCF) E3 ubiquitin ligases. Skp2 (Fbxl1) directly binds to the tumor suppressor p27 in the context of the SCFSkp2 E3 ubiquitin ligase to ubiquitylate and target-phosphorylated p27 for proteasomal degradation. As p27 is a powerful suppressor of growth in a variety of cells, and as Skp2 is also overexpressed in many human cancers, Skp2 is considered an oncogene and an intriguing drug target. However, despite 20 years of investigation, a valid chemical inhibitor of Skp2-mediated degradation of p27 has not been identified...
July 1, 2018: MedChemComm
Hongshun Shi, Hui Li, Ronghua Yuan, Wen Guan, Xiaomei Zhang, Shaoyang Zhang, Wenliang Zhang, Fang Tong, Li Li, Zhihong Song, Changwei Wang, Shulan Yang, Haihe Wang
BACKGROUND: Poly C Binding Protein 1 (PCBP1) is an RNA-binding protein that binds and regulates translational activity of subsets of cellular mRNAs. Depletion of PCBP1 is implicated in various carcinomas, but the underlying mechanism in tumorigenesis remains elusive. METHODS: We performed a transcriptome-wide screen to identify novel bounding mRNA of PCBP1. The bind regions between PCBP1 with target mRNA were investigated by using point mutation and luciferase assay...
August 7, 2018: Journal of Experimental & Clinical Cancer Research: CR
Xing Wang, Chunyan Cheng, Kaijing Zhang, Zhen Tian, Jian Xu, Shuqiong Yang, Qunfeng Lou, Ji Li, Jin-Feng Chen
BACKGROUND: Meloidogyne incognita is a devastating nematode that causes significant losses in cucumber production worldwide. Although numerous studies have emphasized on the susceptible response of plants after nematode infection, the exact regulation mechanism of M. incognita-resistance in cucumber remains elusive. Verification of an introgression line, 'IL10-1', with M. incognita-resistance provides the opportunity to unravel the resistance mechanism of cucumber against M. incognita...
August 3, 2018: BMC Genomics
Mohammad Faujul Kabir, Johari Mohd Ali, Onn Haji Hashim
Background: We have previously reported anticancer activities of Melicope ptelefolia (MP) leaf extracts on four different cancer cell lines. However, the underlying mechanisms of actions have yet to be deciphered. In the present study, the anticancer activity of MP hexane extract (MP-HX) on colorectal (HCT116) and hepatocellular carcinoma (HepG2) cell lines was characterized through microarray gene expression profiling. Methods: HCT116 and HepG2 cells were treated with MP-HX for 24 hr...
2018: PeerJ
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