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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 4, 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...
October 5, 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 M Truskinovsky, Yanmin Chen, Ashley L Mussell, Norma Nowak, Lester Kobzik, Costa Frangou, Jianmin Zhang
Deregulated expression of the transcriptional co-activator 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
Sang-Min Jang, Ya Zhang, Koichi Utani, Haiqing Fu, Christophe E Redon, Anna B Marks, Owen K Smith, Catherine J Redmond, Adrian M Baris, Danielle A Tulchinsky, Mirit I Aladjem
Cell cycle progression in mammals is modulated by two ubiquitin ligase complexes, CRL4 and SCF, which facilitate degradation of chromatin substrates involved in the regulation of DNA replication. One member of the CRL4 complex, the WD-40 containing protein RepID (DCAF14/PHIP), selectively binds and activates a group of replication origins. Here we show that RepID recruits the CRL4 complex to chromatin prior to DNA synthesis, thus playing a crucial architectural role in the proper licensing of chromosomes for replication...
July 17, 2018: Nature Communications
Sara E Meyer, David E Muench, Andrew M Rogers, Tess J Newkold, Emily Orr, Eric O'Brien, John P Perentesis, John G Doench, Ashish Lal, Patrick J Morris, Craig J Thomas, Judy Lieberman, Edwina McGlinn, Bruce J Aronow, Nathan Salomonis, H Leighton Grimes
We have shown that antagomiR inhibition of miRNA miR-21 and miR-196b activity is sufficient to ablate MLL-AF9 leukemia stem cells (LSC) in vivo. Here, we used an shRNA screening approach to mimic miRNA activity on experimentally verified miR-196b targets to identify functionally important and therapeutically relevant pathways downstream of oncogenic miRNA in MLL-r AML. We found Cdkn1b (p27Kip1 ) is a direct miR-196b target whose repression enhanced an embryonic stem cell-like signature associated with decreased leukemia latency and increased numbers of leukemia stem cells in vivo...
August 6, 2018: Journal of Experimental Medicine
Xiaoshuang Wei, Xu Li, Wei Yan, Xinghua Zhang, Yu Sun, Feng Zhang
BACKGROUND/AIMS: SKP2 overexpression has been associated with poor prognosis in numerous cancers. The mechanisms of autophagy in the tumor pathogenesis have been a research focus recently. How the SKP2 involved in autophagy expresses oncogenic characteristics, especially in HCC, are largely unclear. METHODS: The expression of SKP2 was detected by qPCR, Western blot, Immunohistochemical (IHC) and Immunofluorescence (IF) techniques. SKP2 was knocked down or overexpressed by lentivirus transfection in HCC cells...
2018: Cellular Physiology and Biochemistry
Yan Zhang, Xinyi Mu, Rufei Gao, Yanqing Geng, Xueqing Liu, Xuemei Chen, Yuheng Wang, Yubin Ding, Yingxiong Wang, Junlin He
The female reproductive lifespan is largely determined by the size of the primordial follicle pool, which is established early in life. We previously reported that Di (2-ethylhexyl) phthalate (DEHP), an environmental endocrine disruptor and a widely-spreading plasticizer, impairs primordial folliculogenesis. In the present study, we found DEHP significantly altered the number and sex ratio of the offspring of neonatal-exposed mice. Furthermore, by a neonatal exposure model and an ovary culture model, it showed that DEHP activated autophagy in the ovary, with increased autophagy-related gene expression and recognizable autophagosomes, while inhibition of autophagy by 3-MA attenuated the adverse impact of DEHP on primordial folliculogenesis...
September 15, 2018: Journal of Hazardous Materials
Ma'anit Shapira, Eli Kakiashvili, Tzur Rosenberg, Dan D Hershko
After the publication of this work [1], an error was noticed in Fig. 2b, Fig. 3a and Fig. 5b. The Skp1 loading control was accidentally duplicated. We apologize for this error, which did not affect any of the interpretations or conclusions of the article.
July 9, 2018: Breast Cancer Research: BCR
Rachel Brough, Aditi Gulati, Syed Haider, Rahul Kumar, James Campbell, Erik Knudsen, Stephen J Pettitt, Colm J Ryan, Christopher J Lord
Although defects in the RB1 tumour suppressor are one of the more common driver alterations found in triple-negative breast cancer (TNBC), therapeutic approaches that exploit this have not been identified. By integrating molecular profiling data with data from multiple genetic perturbation screens, we identified candidate synthetic lethal (SL) interactions associated with RB1 defects in TNBC. We refined this analysis by identifying the highly penetrant effects, reasoning that these would be more robust in the face of molecular heterogeneity and would represent more promising therapeutic targets...
June 18, 2018: Oncogene
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