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LncRNA pol-lnc78 as a ceRNA regulates antibacterial responses via suppression of pol-miR-n199-3p-mediated SARM down-regulation in Paralichthys olivaceus

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Zoological Research 2024年第1期45卷 25-35页

作者： Xian-Hui Ning Bing Han Ye Peng Shao-Wu Yin College of Marine Science and Engineering Nanjing Normal UniversityNanjingJiangsu 210023China CAS Key Laboratory of experimental Marine biology Center for Ocean Mega-ScienceInstitute of OceanologyChinese Academy of SciencesQingdaoShandong 266071China Co-Innovation Center for Marine Bio-Industry Technology of Jiangsu Province LianyungangJiangsu 222005China

Long non-coding RNAs(lncRNAs)function as key modulators in mammalian immunity,particularly due to their involvement in lncRNA-mediated competitive endogenous RNA(ceRNA)*** their recognized significance in mammals,research on lncRNAs in lower vertebrates remains *** the present study,we characterized the first immune-related lncRNA(pol-lnc78)in the teleost Japanese flounder(Paralichthys olivaceus).Results indicated that pol-lnc78 acted as a ceRNA for pol-miR-n199-3p to target the sterile alpha and armadillo motif-containing protein(SARM),the fifth discovered member of the Toll/interleukin 1(IL-1)receptor(TIR)adaptor *** ceRNA network regulated the antibacterial responses of flounder via the Toll-like receptor(TLR)signaling ***,SARM acted as a negative regulator and exacerbated bacterial infection by inhibiting the expression of inflammatory cytokines IL-1βand tumor necrosis factor-α(TNF-α).Pol-miR-n199-3p reduced SARM expression by specifically interacting with the 3’untranslated region(UTR),thereby promoting SARM-dependent inflammatory cytokine expression and protecting the host against bacterial ***,pol-lnc78 sponged pol-miR-n199-3p to ameliorate the inhibition of SARM *** infection,the negative regulators pol-lnc78 and SARM were significantly down-regulated,while pol-miR-n199-3p was significantly up-regulated,thus favoring host antibacterial *** findings provide novel insights into the mechanisms underlying fish immunity and open new horizons to better understand ceRNA crosstalk in lower vertebrates.

关键词： LncRNA SARM miRNA ceRNA Antibacterial response

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Dual ligand-targeted Pluronic P123 polymeric micelles enhance the therapeutic effect of breast cancer with bone metastases

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Oncology Research 2024年第4期32卷 769-784页

作者： HUAN GAO JIE ZHANG TONY GKLEIJN ZHAOYONG WU BING LIU YUJIN MA BAOYUE DING DONGFENG YIN Jiaxing Key Laboratory for Photonanomedicine and experimental Therapeutics Department of PharmaceuticsCollege of MedicineJiaxing UniversityJiaxing314001China Department of Pharmacy The General Hospital of Xinjiang Military RegionUrumqi830000China Department of Pathology and Medical biology University Medical Center GroningenUniversity of GroningenGroningen9713 GZThe Netherlands Department of Pathology Laboratory of Experimental OncologyErasmus MCRotterdam3015 GDThe Netherlands Department of Pharmacy Jiaxing Maternal and Child Health Care HospitalAffiliated Hospital of Jiaxing UniversityJiaxing314001China Qinghai Enlu Biotechnology Co. Ltd.Haidong810700China

Bone metastasis secondary to breast cancer negatively impacts patient quality of life and *** treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic *** improve the treatment efficacy,we developed Pluronic P123(P123)-based polymeric micelles dually decorated with alendronate(ALN)and cancer-specific phage protein DMPGTVLP(DP-8)for targeted drug delivery to breast cancer bone ***(DOX)was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity(3.44%).The DOX-loaded polymeric micelles were spherical,123 nm in diameter on average,and exhibited a narrow size *** in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX *** micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated *** binding of the micelles to hydroxyapatite(HA)microparticles indicated their high affinity for bone.P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis *** vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic *** conclusion,our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.

关键词： Pluronic micelles Targeted nanotherapeutics Nanoparticulate drug delivery system Breast cancer with bone metastasis Therapeutic efficacy

Histone deacetylase inhibitors for treatment of hepatocellular carcinoma

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Acta Pharmacologica Sinica 2005年第9期26卷 1025-1033页

作者： Danila CORADINI Annalisa SPERANZA uo tumor biology and experimental therapy Department of experimental Oncology Istituto Nazionale per lo Studio e la Cura dei tumori 20133 Milan Italy uo tumor biology and experimental therapy Department of experimental Oncology Istituto Nazionale per lo Studio e la Cura dei tumori 20133 Milan Italy

Hepatocellular carcinoma(HCC)is one of the most common cancers in the *** resection has been considered the optimal treatment approach,but onlya small proportion of patients are suitable candidates for surgery,and the relapserate is *** to prevent recurrence,including chemoemboliza-tionbefore and adjuvant therapy after surgery,have proven to have a limited benefit;liver transplantation is successful in treating limited-stage HCC because only aminority of patients qualify for ***,new therapeutic strat-egies are urgently *** in addition to the classical genetic mecha-nisms of deletion or inactivating point mutations,epigenetic alterations,such ashyperacetylation of the chromatin-associated histones(responsible for genesilencing),are believed to be involved in the development and progression ofHCC,novel compounds endowed with a histone deacetylase(HDAC)inhibitoryactivity are an attractive therapeutic *** particular,pre-clinical resultsobtained using HA-But,an HDAC inhibitor in which butyric acid residues areesterified to a hyaluronic acid backbone and characterized by a high affinity forthe membrane receptor CD44,indicated that this class of compounds may repre-sent a promising approach for hepatocellular carcinoma treatment.

关键词： hepatocellular carcinoma histone deace-tylase inhibitors cancer therapy

Cancer cell cycle heterogeneity as a critical determinant of therapeutic resistance

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Genes & Diseases 2024年第1期11卷 189-204页

作者： Ebrahim H.Maleki Ahmad Reza Bahrami Maryam M.Matin Department of biology Faculty of ScienceFerdowsi University of Mashhad*** MashhadIran Jagiellonian Centre for experimental Therapeutics(JCET) Jagiellonian University31-007 KrakowPoland Doctoral School of Exact and Natural Sciences Jagiellonian University30-348 KrakowPoland Industrial Biotechnology Research Group Institute of BiotechnologyFerdowsi University of Mashhad*** MashhadIran Novel Diagnostics and Therapeutics Research Group Institute of BiotechnologyFerdowsi University of Mashhad***MashhadIran Stem Cell and Regenerative Medicine Research Group Iranian Academic Center for EducationCulture and Research(ACECR)Khorasan Razavi Branch917751376 MashhadIran

Intra-tumor heterogeneity is now arguably one of the most-studied topics in tumor biology,as it represents a major obstacle to effective cancer *** tumor cells are highly diverse at genetic,epigenetic,and phenotypic levels,intra-tumor heterogeneity can be assumed as an important contributing factor to the nullification of chemotherapeutic effects,and recurrence of the *** on the role of heterogeneous subpopulations of cancer cells with varying cell-cycle dynamics and behavior during cancer progression and treatment;herein,we aim to establish a comprehensive definition for adaptation of neoplastic cells against *** discuss two parallel and yet distinct subpopulations of tumor cells that play pivotal roles in reducing the effects of chemotherapy:"resistant"and"tolerant"***,this review also highlights the impact of the quiescent phase of the cell cycle as a survival mechanism for cancer *** understanding the mechanisms under-lying the quiescence,it provides an insightful perspective on cancer stem cells(CsCs)and their dual and intertwined functions based on their cell cycle state in response to ***-over,CSCs,epithelial-mesenchymal transformed cells,circulating tumor cells(CTCs),and disseminated tumor cells(DTCs),which are mostly in a quiescent state of the cell cycle are proved to have multiple biological links and can be implicated in our viewpoint of cell cycle heterogeneity in ***,increasing our knowledge of cell cycle heterogeneity is a key to identifying new therapeutic solutions,and this emerging concept may provide us with new opportunities to prevent the dreadful cancer recurrence.

关键词： Cancer stem cells(CSCs) Carcinoma Cell cycle heterogeneity Quiescence therapy resistance therapy tolerance tumor dormancy

Oyster studies reveal the duplication and functional diversification of Bivalvia caspase-8 genes

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Journal of Oceanology and Limnology 2023年第3期41卷 1109-1121页

作者： Shaoxi DENG Tao QU Guofan ZHANG Fei XU CAS and Shandong Province Key Laboratory of experimental Marine biology Center for Ocean Mega-ScienceInstitute of OceanologyChinese Academy of SciencesQingdao 266071China University of Chinese Academy of Sciences Beijing 100049China Laboratory for Marine biology and Biotechnology Qingdao National Laboratory for Marine Science and TechnologyQingdao 266000China NHC Key Laboratory of Diagnosis and therapy of Gastrointestinal tumor Gansu Provincial HospitalLanzhou 730000China

Caspase-8,first classified as a pro-apoptotic caspase,is considered to have arisen from duplication with caspase-10 and involves multiple immune and inflammatory responses in ***,few are known on the phylogeny and function of caspase-8 in molluscs,one of the largest phyla in marine *** this study,we conducted phylogenetic and functional analysis on molluscan caspase-8-like *** indicate that duplication occurred in molluscan caspase-8-like genes,resulting in at least two caspase-8 copies in some groups of *** studies in Pacific oyster Crassostrea gigas showed different spatio-temporal expression patterns and subcellular localizations of CgCaspase-8-1 and *** no interaction was observed between CgCaspase-8-2 and CgFADD,the adaptor molecule in apoptosis,yeast two-hybrid and co-immunoprecipitation assays suggested the interaction between CgCaspase-8-1 and CgFADD,indicating its pro-apoptotic *** addition,CgCaspase-8-1 showed interaction with the CARD domain of *** with two NF-κB subunits(Cgp105 and CgRel),their transcripts were up-regulated in response to poly(I:C)stimuli,supporting the immune function of both pro-and *** results provide insight into the evolution and functional diversification of Bivalvia caspase-8 genes.

关键词： caspase-8 apoptosis metamorphosis inflammation Crassostrea gigas

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Let-7i-5p maintains the stemness via R-spondin2/Wnt pathway in hepatocellular carcinoma

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Genes & Diseases 2024年第4期11卷 20-23页

作者： Qinghua Wei Xueshan Dai Jiahui Wei Wenwei Sun Xiaoqian Yang Yuxin Zhang Xin Guo Yi Chen College of Pharmaceutical Sciences&Chinese Medicine Southwest UniversityChongqing 400716China Center for Basic Medical Research TEDA International Cardiovascular HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300457China Chongqing Key Laboratory of New Drug Screening from Traditional Chinese Medicine Chongqing 400716China pharmacology of Chinese Materia Medica-the Key Discipline Constructed by the State Administration of Traditional Chinese Medicine Chongqing 400716China Division of Cell Developmental and Integrative BiologySchool of MedicineSouth China University of TechnologyGuangzhouGuangdong 510006China National Demonstration Center for experimental Pharmacy Education(Southwest University) Chongqing 400716China Engineering Research Center of Coptis Development and Utilization(Ministry of Education) College of Pharmaceutical Sciences and Chinese MedicineSouthwest UniversityChongqing 400716China

Cancer stem cells(CSCs)are related to tumorigenesis,recurrence,metastasis,and drug resistance in hepatocellular carcinoma(HCC).1 Let-7i is a noncoding small RNA,belonging to the famous miRNA let-7 ***,let-7i has been ... 详细信息

关键词： hepatocellular Cancer metastasis

Targeting stroma and tumor,silencing galectin 1 treats orthotopic mouse hepatocellular carcinoma

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Acta Pharmaceutica Sinica B 2024年第1期14卷 292-303页

作者： Tahereh Setayesh Ying Hu Farzam Vaziri Xin Chen Jinping Lai Dongguang Wei Yu-Jui Yvonne Wan Department of Medical Pathology and Laboratory Medicine University of CaliforniaDavisSacramentoCA 95817USA Cancer biology Program the University of Hawaii Cancer CenterHonoluluHI 96813USA Department of Pathology and Laboratory Medicine Kaiser Permanente Sacramento Medical CenterSacramentoCA 95825USA

This study examines inhibiting galectin 1(Gal1)as a treatment option for hepatocellular carcinoma(HCC).Gal1 has immunosuppressive and cancer-promoting *** data showed that Gal1 was highly expressed in human and mouse *** levels of Gal1 positively correlated with the stages of human HCC and negatively with *** roles of Gal1 in HCC were studied using overexpression(OE)or silencing using Igals1 siRNA delivered by *** to HCC initiation induced by RAS and AKT mutations,lgals1-OE and silencing had opposite impacts on tumor *** treatment effect of lgals1 siRNAwas further demonstrated by intersecting HCC at different time points when the tumor load had already reached 9%or even 42%of the body *** spatial transcriptomic profiles of Gal1 silenced and OE HCC,inhibiting matrix formation and recognition of foreign antigen in CD45t cell-enriched areas located at tumor-margin likely contributed to the anti-HCC effects of Gal1 *** the tumors,silencing Gal1 inhibited translational initiation,elongation,and ***,Gal1 silencing increased immune cells as well as expanded cytotoxic T cells within the tumor,and the anti-HCC effect of lgals1 siRNAwas ***,Gal1 silencing has a promising potential for HCC treatment.

关键词： Liver Hepatocellular carcinoma Carbohydrate-binding lectin Galectin 1 Extracellular matrix Translation Spatial transcriptomics tumor-margin

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Targeting hormone-resistant breast cancer cells with docetaxel:a look inside the resistance

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Cancer Drug Resistance 2023年第1期6卷 103-115页

作者： Alexander M.Scherbakov Anna A.Basharina Danila V.Sorokin Ekaterina I.Mikhaevich Iman E.Mizaeva Alexandra L.Mikhaylova Tatiana A.Bogush Mikhail A.Krasil’nikov Department of experimental tumor biology Blokhin N.N.National Medical Research Center of OncologyMoscow 115522Russian Federation Group of Molecular tumor Markers Blokhin N.N.National Medical Research Center of OncologyMoscow 115522Russian Federation

Aim:The study aims to analyze the effect of long-term incubation of ERα-positive MCF7 breast cancer cells with 4-hydroxytamoxifen(HT)on their sensitivity to tubulin polymerization inhibitor ***:The analysis of cell viability was performed by the MTT *** expression of signaling proteins was analyzed by immunoblotting and flow ***αactivity was evaluated by gene reporter *** establish hormone-resistant subline MCF7,breast cancer cells were treated with 4-hydroxytamoxifen for 12 ***:The developed MCF7/HT subline has lost sensitivity to 4-hydroxytamoxifen,and the resistance index was *** Akt activity(2.2-fold)and decreased ERαexpression(1.5-fold)were revealed in MCF7/HT *** activity of the estrogen receptorαwas reduced(1.5-fold)in MCF7/*** of class Ⅲβ-tubulin expression(TUBB3),a marker associated with metastasis,revealed the following trends:higher expression of TUBB3 was detected in triple-negative breast cancer MDA-MB-231 cells compared to hormone-responsive MCF7 cells(Ptherapy for hormone-resistant cancer looks highly promising,especially for cancers with low TUBB3 expression.

关键词： Cancer docetaxel 4-hydroxytamoxifen classⅢβ-tubulin resistance breast cancer estrogen receptors alpha

Targeting PKM2 signaling cascade with salvianic acid A normalizes tumor blood vessels to facilitate chemotherapeutic drug delivery

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2077-2096页

作者： Cheng Qian Yueke Zhou Teng Zhang Guanglu Dong Mengyao Song Yu Tang Zhonghong Wei Suyun Yu Qiuhong Shen Wenxing Chen Jaesung P.Choi Juming Yan Chongjin Zhong Li Wan Jia Li Aiyun Wang Yin Lu Yang Zhao Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica Nanjing University of Chinese MedicineNanjing 210023China School of Medicine&Holistic Integrative Medicine Nanjing University of Chinese MedicineNanjing 210023China Centre for Inflammation Faculty of ScienceCentenary InstituteSchool of Life SciencesUniversity of Technology SydneySydney NSW 2050Australia Jiangsu Key Laboratory of Immunity and Metabolism Department of Pathogenic Biology and ImmunologyNational Experimental Demonstration Center for Basic Medicine EducationXuzhou Laboratory of Infection and ImmunityXuzhou Medical UniversityXuzhou 221004China Department of General Surgery Jiangsu Province Hospital of Chinese MedicineAffiliated Hospital of Nanjing University of Chinese MedicineNanjing 210029China Macquarie Medical School Faculty of MedicineHuman Health SciencesMacquarie UniversitySydney NSW 2109Australia

Aberrant tumor blood vessels are prone to propel the malignant progression of tumors,and targeting abnormal metabolism of tumor endothelial cells emerges as a promising option to achieve vascular normalization and antagonize tumor ***,we demonstrated that salvianic acid A(SAA)played a pivotal role in contributing to vascular normalization in the tumor-bearing mice,thereby improving delivery and effectiveness of the chemotherapeutic *** was capable of inhibiting glycolysis and strengthening endothelial junctions in the human umbilical vein endothelial cells(HUVECs)exposed to ***,SAA was inclined to directly bind to the glycolytic enzyme PKM2,leading to a dramatic decrease in endothelial *** importantly,SAA improved the endothelial integrity via activating theβ-Catenin/Claudin-5 signaling axis in a PKM2-dependent *** findings suggest that SAA may serve as a potent agent for inducing tumor vascular normalization.

关键词： Salvianic acid A tumor vascular normalization PKM2 β-Catenin Claudin-5 Endothelial glycolysis Tight junctions Doxorubicin