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Protein translation:biological processes and therapeutic strategies for human diseases

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1048-1064页

作者： Xuechao Jia Xinyu He Chuntian Huang Jian Li Zigang Dong Kangdong Liu Department of Pathophysiology School of Basic Medical SciencesAcademy of Medical SciencesZhengzhou UniversityZhengzhouHenan 450000China China-US(Henan)Hormel Cancer Institute ZhengzhouHenan 450000China Department of Pathology and Pathophysiology Henan University of Chinese MedicineZhengzhouHenan 450000China Tianjian laboratory of Advanced Biomedical Sciences ZhengzhouHenan 450052China Research Center for Basic Medicine Sciences Academy of Medical SciencesZhengzhou UniversityZhengzhou 450052 HenanChina Provincial Cooperative Innovation Center for Cancer chemoprevention Zhengzhou UniversityZhengzhouHenan 450000China State Key laboratory of Esophageal Cancer Prevention and Treatment Zhengzhou UniversityZhengzhouHenan 450000China The Collaborative Innovation Center of Henan Province for Cancer chemoprevention ZhengzhouHenan 450000China

Protein translation is a tightly regulated cellular process that is essential for gene expression and protein *** deregulation of this process is increasingly recognized as a critical factor in the pathogenesis of various human *** this review,we discuss how deregulated translation can lead to aberrant protein synthesis,altered cellular functions,and disease *** explore the key mechanisms contributing to the deregulation of protein translation,including functional alterations in translation factors,tRNA,mRNA,and ribosome *** translation leads to abnormal protein expression,disrupted cellular signaling,and perturbed cellular functions-all of which contribute to disease *** development of ribosome profiling techniques along with mass spectrometry-based proteomics,mRNA sequencing and single-cell approaches have opened new avenues for detecting diseases related to translation ***,we highlight recent advances in therapies targeting translation-related disorders and their potential applications in neurodegenerative diseases,cancer,infectious diseases,and cardiovascular ***,the growing interest lies in targeted therapies aimed at restoring precise control over translation in diseased cells is *** conclusion,this comprehensive review underscores the critical role of protein translation in disease and its potential as a therapeutic *** in understanding the molecular mechanisms of protein translation deregulation,coupled with the development of targeted therapies,offer promising avenues for improving disease outcomes in various human ***,it will unlock doors to the possibility of precision medicine by offering personalized therapies and a deeper understanding of the molecular underpinnings of diseases in the future.

关键词： translation offering precise

Downregulation of KCTD12 contributes to melanoma stemness by modulating CD271

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Cancer Biology & Medicine 2019年第3期16卷 498-513页

作者： Weiyu Shen Yumei Li Bifei Li Liping Zheng Xiaodong Xie Jingqing Le Yusheng Lu Tao Li Fan Chen Lee Jia Cancer Metastasis Alert and Prevention Center College of Chemistry and Fujian Provincial Key Laboratory of CancerMetastasis Chemoprevention and ChemotherapyFuzhou UniversityFuzhou350108China Department of Pharmacy Fujian Provincial Maternity and Children’s HospitalFuzhou350001China Institute of Oceanography Minjiang UniversityFuzhou350108China

Objective: Cancer metastasis remains the primary cause of cancer-related death *** a previous study, we found that levels of BTB/POZ domain-containing protein KCTD12 are lower in metastatic melanoma cells than in parental melanoma *** purpose of this study was to identify the roles of KCTD12 in cancer ***: The Cancer Genome Atlas(TCGA) datasets were used to evaluate the relationship between KCTD12 and skin cutaneous melanoma(SKCM) *** effects of endogenous KCTD12 on biological behaviors were examined using the MTT *** impacts of KCTD12 on melanoma stemness were explored using spheroid formation ***12 knockout A375 cells were generated to confirm the inhibitory effect of KCTD12 on CD271, and a mouse metastatic model was used to determine the impact of KCTD12 on melanoma metastasis in ***: KCTD12 levels were lower in lung metastatic cells than in paired parental melanoma cells, and low KCTD12 expression indicated a poor prognosis in *** metastasis-related capacities were higher in lung metastatic cells than in parental melanoma ***, KCTD12 knockdown enhanced tumor growth and metastasis both in vitro and in ***, the interaction between KCTD12 and CD271 might be responsible for the stemness transformation after KCTD12 ***: This study identifies for the first time the role of the interaction between KCTD12 and CD271 in inducing melanoma cell stemness ***, KCTD12 repression enhances melanoma cell growth, adhesion, migration and invasion.

关键词： KCTD12 MITF CD271 melanoma cancer metastasis cancer stem cell

专题报告-S4氧化应激与DNA损伤信号途径

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中国药理学与毒理学杂志 2006年第3期20卷 172-174页

作者： Young Joon SURH National Research laboratory of Molecular Carcinogenesis and chemoprevention College of PharmacySeoul National University Seoul 151-742 Korea

Reactive oxygen species （ROS） and reactive nitrogen species （RNS） can cause cellular damage implicated in pathogenesis of a wide range of human disorders, including cancer, autoimmune disease, diabetes, cardiovasc... 详细信息

关键词： Oxidative Stress DNA Damage Signaling Reactive oxygen species

Novel wild edible mushroom Astraeus hygrometricus(Pers.)Morgan induces robust apoptosis on human acute lymphoblastic leukemia cells through a RONS-subsisted mitochondria-dependent pathway

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Journal of Traditional Chinese Medical Sciences 2024年第1期11卷 67-77页

作者： Amrita Pal Ribhu Ray Anirban Chouni Subhadip Hajra Santanu Paul Department of Botany University of CalcuttaKolkata 700019India Department of Cancer chemoprevention Chittaranjan National Cancer InstituteKolkata 700026India

Objective:To explore the therapeutic effects of the novel wild edible mushroom Astraeus hygrometricus(Pers.)Morgan(***)on human acute lymphoblastic leukemia ***:Extensive screening of the antiproliferative and chemopreventive potential of different extracts from 5 wild mushrooms,***,Phallus sp.,Lentinus sp.,Tricholoma sp.,and Serpula *** performed against a panel of 6 cancer cell lines and normal cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)*** determination,cell cycle profiling,intracellular reactive oxygen species(ROS)and reactive nitrogen species(RNS),and mitochondrial membrane potential were analyzed by flow *** activity of caspases was measured colorimetrically,and the expression pattern of mitochondrial proteins was ***:The methanol extract of *** and MOLT-4 cells were identified as the most potent extract exhibiting antiproliferative activity and most sensitive cell line,*** mushroom extract induced robust selective apoptosis in MOLT-4 cells and arrested cell cycle progression at the G0/G1 *** extract disrupted the mitochondrial membrane potential and enhanced ROS production in MOLT-4 *** methanol extract induced apoptosis by downregulating the expression of Bcl-2,increasing the expression of Bax,and activating the caspase ***:The novel wild edible mushroom is a potential repository of biomolecules for the development of antileukemic drugs.

关键词： Mushroom Astraeus hygrometricus(Pers.)Morgan Apoptosis Antileukemic

Non-coding RNA as future target for diagnose and treatment of perineural invasion in cancers

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BIOCELL 2024年第6期48卷 923-934页

作者： BINGJIE LI WENBO CAO JINJING XIAO YIXIAO CHEN QIYING WEI MINGJIN YUE SAIJUN MO Department of Pathophysiology School of Basic Medical SciencesZhengzhou UniversityZhengzhouChina Collaborative Innovation Center of Henan Province for Cancer chemoprevention ZhengzhouChina State Key laboratory of Esophageal Cancer Prevention and Treatment ZhengzhouChina Department of Research and Development Henan Tianxing Education and Media Company LimitedZhengzhouChina

Perineural invasion(PNI),a particularly insidious form of tumor metastasis distinct from hematogenous or lymphatic spread,has the capacity to extend well beyond the primary tumor site,inﬁltrating distant regions devoid of lymphatic or vascular *** often heralds a decrease in patient survival rates and is recognized as an indicator of an unfavorable prognosis across a variety of *** its clinical signiﬁcance,the underlying molecular mechanisms of PNI remain elusive,complicating the development of speciﬁc and efﬁcacious diagnostic and therapeutic *** the realm of cancer research,non-coding RNAs(ncRNAs)have attracted considerable attention due to their multifaceted roles and cancer-speciﬁc expression proﬁles,positioning them as promising candidates for applications in cancer diagnostics,prognostics,and *** the various types of ncRNAs,microRNAs(miRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs)have emerged as inﬂuential players in *** involvement is increasingly recognized as a contributing factor to tumor progression and therapeutic *** study synthesizes and explores the diverse functions and mechanisms of ncRNAs in relation to PNI in *** comprehensive review aims to shed light on cutting-edge perspectives that could pave the way for innovative diagnostic and therapeutic approaches to address the challenges posed by PNI in oncology.

关键词： Perineural invasion Non-coding RNA Diagnose and treatment Cancer Biomarker

Erianin suppresses constitutive activation of MAPK signaling pathway by inhibition of CRAF and MEK1/2

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Signal Transduction and Targeted Therapy 2023年第4期8卷 1874-1888页

作者： Penglei Wang Xuechao Jia Bingbing Lu Han Huang Jialin Liu Xuejiao Liu Qiong Wu Yamei Hu Pan Li Huifang Wei Tingting Liu Dengyun Zhao Lingwei Zhang Xueli Tian Yanan Jiang Yan Qiao Wenna Nie Xinli Ma Ruihua Bai Cong Peng Zigang Dong Kangdong Liu Department of Pathophysiology Basic Medicine Research CenterSchool of Basic Medical SciencesAMSZhengzhou University450000 ZhengzhouChina China-US(Henan)Hormel Cancer Institute 450000 ZhengzhouChina The Department of Pathology Affiliated Cancer Hospital of Zhengzhou University450000 ZhengzhouChina The Department of Dermatology Xiangya HospitalCentral South University410078 ChangshaChina The Collaborative Innovation Center of Henan Province for Cancer chemoprevention 450000 ZhengzhouChina State Key laboratory of Esophageal Cancer Prevention and Treatment Zhengzhou University450000 ZhengzhouChina Provincial Cooperative Innovation Center for Cancer chemoprevention Zhengzhou UniversityZhengzhouChina

Constitutive activation of RAS-RAF-MEK-ERK signaling pathway(MAPK pathway)frequently occurs in many cancers harboring RAS or RAF oncogenic *** of the paradoxical activation induced by a single use of BRAF or MEK inhibitors,dual-target RAF and MEK treatment is thought to be a promising *** this work,we evaluated erianin is a novel inhibitor of CRAF and MEK1/2 kinases,thus suppressing constitutive activation of the MAPK signaling pathway induced by BRAF V600E or RAS *** enzyme profiling,surface plasmon resonance(SPR),isothermal titration calorimetry(ITC),cellular thermal shift assay,computational docking,and molecular dynamics simulations were utilized to screen and identify erianin binding to CRAF and MEK1/*** assay,luminescent ADP detection assay,and enzyme kinetics assay were investigated to identify the efficiency of erianin in CRAF and MEK1/2 kinase ***,erianin suppressed BRAF V600E or RAS mutant melanoma and colorectal cancer cell by inhibiting MEK1/2 and CRAF but not BRAF kinase ***,erianin attenuated melanoma and colorectal cancer in ***,we provide a promising leading compound for BRAF V600E or RAS mutant melanoma and colorectal cancer through dual targeting of CRAF and MEK1/2.

关键词： MEK1/2 BRAF activation

Inhibiting autophagy enhances sulforaphane-induced apoptosis via targeting NRF2 in esophageal squamous cell carcinoma

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Acta Pharmaceutica Sinica B 2021年第5期11卷 1246-1260页

作者： Zhaoming Lu Yandan Ren Li Yang Ang Jia Yi Hu Yu Zhao Wuduo Zhao Bin Yu Wen Zhao Jianying Zhang Guiqin Hou State Key laboratory of Esophageal Cancer Prevention&Treatment School of Pharmaceutical SciencesZhengzhou UniversityZhengzhou 450001China Collaborative Innovation Center of Cancer chemoprevention Zhengzhou 450001China Center of Advanced Analysis&Gene Sequencing Zhengzhou UniversityZhengzhou 450001China Henan Academy of Medical and Pharmaceutical Sciences Zhengzhou UniversityZhengzhou 450052China Key laboratory of Advanced Drug Preparation Technologies Ministry of EducationZhengzhou UniversityZhengzhou 450001China

Sulforaphane(SFN), a natural anti-tumor compound from cruciferous vegetables, has been reported to induce protective autophagy to cancer cells, which might impair the anti-tumor efficiency of SFN. However, the accurate function and mechanism of SFN inducing autophagy in cancers are still obscure, especially in esophageal squamous cell carcinoma(ESCC), one of malignancies with high incidence in North China. Here, we mainly explored the potential function of autophagy upon SFN treatment in ESCC and molecular mechanism. We demonstrated that SFN could inhibit cell proliferation and induce apoptosis by activating caspase pathway. Moreover, we found activation of NRF2 pathway by SFN was responsible for the induction of autophagy and also a disadvantage element to the anti-tumor effects of SFN on ESCC, indicating that SFN might induce protective autophagy in ESCC. We, therefore,investigated effects of autophagy inhibition on sensitivity of ESCC cells to SFN and found that chloroquine(CQ) could neutralize the activation of SFN on NRF2 and enhance the activation of SFN on caspase pathway, thus improved the anti-tumor efficiency of SFN on ESCC in vitro and in vivo. Our study provides a preclinical rationale for development of SFN and its analogs to the future treatment of ESCC.

关键词： Sulforaphane Autophagy Chloroquine NRF2 Esophageal squamous cell carcinoma

Targets and molecular mechanisms of a citrus flavonoid, hesperidin, against luminal breast cancer cells: an integrative bioinformatics analysis

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Asian Pacific Journal of Tropical Biomedicine 2019年第12期9卷 531-538页

作者： Adam Hermawan Herwandhani Putri Department of Pharmaceutical Chemistry Faculty of PharmacyUniversitas Gadjah MadaSekip Utara Ⅱ55281 YogyakartaIndonesia Cancer chemoprevention Research Center Faculty of PharmacyUniversitas Gadjah MadaSekip Utara Ⅱ55281 YogyakartaIndonesia

Objective:To identify the potential target and mechanisms of hesperidin in MCF-7 estrogen receptor-positive breast cancer cells using bioinformatics ***:Gene expression profiles were accessed from public database *** Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was carried out with Database for Annotation,Visualization and Integrated *** protein-protein interaction network was analyzed by STRING-DB and visualized by *** factor regulatory networks were constructed from TRED,TRRUST,Reg Network and visualized by *** association analysis was conducted by Web ***:GO and KEGG pathway enrichment analysis revealed biological processes,cellular components and molecular functions that were related to cancer and estrogen signaling *** pathway enrichment analysis of the genes in transcription factor-differential expression genes regulatory network showed regulation of cancer,estrogen signaling pathways,epidermal growth factor receptor tyrosine kinase inhibitor resistance,and endocrine ***,drug association analysis revealed that hesperidin affected the expression of the same gene as ***:Hesperidin targets estrogen receptor signaling in estrogen receptor-positive breast cancer *** of this study could trace the molecular mechanism of hesperidin in estrogen receptor-positive breast cancer cells and integrative bioinformatics analysis could accelerate drug discovery and development.

关键词： Hesperidin Breast cancer Bioinformatics Estrogen receptor Signaling pathway

Achyranthes bidentata polysaccharide can safely prevent NSCLC metastasis via targeting EGFR and EMT

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Signal Transduction and Targeted Therapy 2020年第1期5卷 982-985页

作者： Chunlian Zhong Jingyi Yang Yusheng Lu Huanzhang Xie Shengyi Zhai Chen Zhang Zhiying Luo Xuanchen Chen Xuanmo Fang Lee Jia Institute of Oceanography Minjiang UniversityFuzhouFujian 350108China Cancer Metastasis Alert and Prevention Center College of ChemistryFujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and ChemotherapyFuzhou UniversityFuzhouFujian 350116China Fujian Provincial People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine Fuzhou 350004China

Dear Editor,Cancer metastasis,dissemination of cancer cells from primary tumors to distant sites,attributes to 90%cancer-related death.1 Although the targeted therapies,bio-nanomaterial-based target delivery,and the consequent adoption of the so-called personalized medicine have obtained notable achievements in some cancers,significant problems still exist with these approaches.2 There are hardly any cancer therapeutic agents that can interfere with metastasized *** recent times,we proposed a novel concept,namely cancer metastasis chemoprevention,which is different from the existing cancer chemotherapy and cancer *** metastasis chemoprevention aims at safely preventing circulating tumor cells(CTCs)and related molecules from gemmating into the metastatic *** strategy does not intend to kill cancer cells as cancer chemotherapy does,nor to aimlessly prevent cancers from carcinogenesis as cancer chemoprevention does.

关键词： metastasis prevention chemotherapy