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BCL7C suppresses ovarian cancer growth by inactivating mutant p53

Journal of Molecular Cell Biology 2021年第2期13卷 141-150页

作者： Canhua Huang Qian Hao Getao Shi Xiang Zhou Yu Zhang Gynecological Oncology Research and Engineering Center of Hunan Province Changsha 410008China Department of Gynecology Xiangya HospitalCentral South UniversityChangsha 410008China Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences Fudan UniversityShanghai 200032China Key Laboratory of Breast Cancer in Shanghai Fudan University Shanghai Cancer CenterFudan UniversityShanghai 200032China School of Life Sciences Shaoxing UniversityShaoxing 312000China

B-cell CLL/lymphoma 7 protein family member C (BCL7C) located at chromosome 16p11.2 shares partial sequence homology with the other two family members, BCL7A and BCL7B. Its role in cancer remains completely unknown. Here, we report our finding of its tumor-suppressive role in ovarian cancer. Supporting this is that BCL7C is downregulated in human ovarian carcinomas, and its underexpression is associated with unfavorable prognosis of ovarian cancer as well as some other types of human cancers. Also, ectopic BCL7C restrains cell proliferation and invasion of ovarian cancer cells. Consistently, depletion of BCL7C reduces apoptosis and promotes cell proliferation and invasion of these cancer cells. Mechanistically, BCL7C suppresses mutant p53-mediated gene transcription by binding to mutant p53, while knockdown of BCL7C enhances the expression of mutant p53 target genes in ovarian cancer cells. Primary ovarian carcinomas that sustain low levels of BCL7C often show the elevated expression of mutant p53 target genes. In line with these results, BCL7C abrogates mutant p53-induced cell proliferation and invasion, but had no impact on proliferation and invasion of cancer cells with depleted p53 or harboring wild-type p53. Altogether, our results demonstrate that BCL7C can act as a tumor suppressor to prevent ovarian tumorigenesis and progression by counteracting mutant p53 activity.

关键词： BCL7C mutant p53 apoptosis invasion ovarian cancer

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CNMa-CNMa receptor at microbiome-gut-brain axis:novel target to regulate feeding decision

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Signal Transduction and Targeted Therapy 2021年第8期6卷 2275-2277页

作者： Liyuan Peng Hai-Yan Yin Canhua Huang School of Basic Medical Sciences Chengdu University of Traditional Chinese MedicineChengduChina State Key Laboratory of Biotherapy and Cancer Center West China Hospitaland West China School of Basic Medical Sciences&Forensic MedicineSichuan Universityand Collaborative Innovation Center for BiotherapyChengduChina lnternational Collaborative Centre on Big Science Plan for Purinergic Signalling Chengdu University of Traditional Chinese MedicineChengduChina Acupuncture and Chronobiology Key Laboratory of Sichuan Province ChengduChina

A recent study published in Nature by Kim et al.discovers that the CNMamide(CNMa)-CNMa receptor(CNMaR)axis plays a crucial regulatory role in response to deprivation of diet-and microbiome-derived amino acid in Drosophila.In detail,gut enterocytes detect and respond to protein limitation through upregulating CNMa expression and communicating with CNMaR-expressing neurons in the brain(Fig.1).

关键词： CNM expressing

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Neoantigens:promising targets for cancer therapy

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Signal Transduction and Targeted Therapy 2023年第2期8卷 446-483页

作者： Na Xie Guobo Shen Wei Gao Zhao huang Canhua Huang Li Fu State Key Laboratory of Biotherapy and Cancer Center West China Hospitaland West China School of Basic Medical Sciences and Forensic MedicineSichuan Universityand Collaborative Innovation Center for BiotherapyChengdu610041China Clinical Genetics Laboratory Affiliated Hospital&Clinical Medical College of Chengdu UniversityChengdu610081China Guangdong Provincial Key Laboratory of Regional Immunity and Diseases Department of Pharmacology and International Cancer CenterShenzhen University Health Science CenterShenzhen518060GuangdongPeople’s Republic of China

Recent advances in neoantigen research have accelerated the development and regulatory approval of tumor immunotherapies,including cancer vaccines,adoptive cell therapy and antibody-based therapies,especially for solid tumors.Neoantigens are newly formed antigens generated by tumor cells as a result of various tumor-specific alterations,such as genomic mutation,dysregulated RNA splicing,disordered post-translational modification,and integrated viral open reading frames.Neoantigens are recognized as non-self and trigger an immune response that is not subject to central and peripheral tolerance.The quick identification and prediction of tumor-specific neoantigens have been made possible by the advanced development of next-generation sequencing and bioinformatic technologies.Compared to tumor-associated antigens,the highly immunogenic and tumor-specific neoantigens provide emerging targets for personalized cancer immunotherapies,and serve as prospective predictors for tumor survival prognosis and immune checkpoint blockade responses.The development of cancer therapies will be aided by understanding the mechanism underlying neoantigen-induced anti-tumor immune response and by streamlining the process of neoantigen-based immunotherapies.This review provides an overview on the identification and characterization of neoantigens and outlines the clinical applications of prospective immunotherapeutic strategies based on neoantigens.We also explore their current status,inherent challenges,and clinical translation potential.

关键词： antigens alterations approval

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Oxidative stress and diabetes:antioxidative strategies

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Frontiers of Medicine 2020年第5期14卷 583-600页

作者： Pengju Zhang Tao Li Xingyun Wu Edouard C.Nice Canhua Huang Yuanyuan Zhang Department of Pharmacology West China School of Basic Medical Sciences&Forensic MedicineSichuan UniversityChengdu 610041China Department of Biochemistry and Molecular Biology Monash UniversityClaytonVictoriaAustralia

Diabetes mellitus is one of the major public health problems worldwide.Considerable recent evidence suggests that the cellular reduction-oxidation(redox)imbalance leads to oxidative stress and subsequent occurrence and development of diabetes and related complications by regulating certain signaling pathways involved in p-cell dysfunction and insulin resistance.Reactive oxide species(ROS)can also directly oxidize certain proteins(defined as redox modification)involved in the diabetes process.There are a number of potential problems in the clinical application of antioxidant therapies including poor solubility,storage instability and nonselectivity of antioxidants.Novel antioxidant delivery systems may overcome pharmacokinetic and stability problem and improve the selectivity of scavenging ROS.We have therefore focused on the role of oxidative stress and antioxidative therapies in the pathogenesis of diabetes mellitus.Precise therapeutic interventions against ROS and downstream targets are now possible and provide important new insights into the treatment of diabetes.

关键词： diabetes oxidative stress redox modification antioxidative therapy novel antioxidant delivery

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Insights and implications of sexual dimorphism in osteoporosis

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Bone Research 2024年第1期12卷 20-49页

作者： Yuan-Yuan Zhang Na Xie Xiao-Dong Sun Edouard C.Nice Yih-Cherng Liou Canhua Huang Huili Zhu Zhisen Shen Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China West China School of Basic Medical Sciences&Forensic Medicine Sichuan UniversityChengdu 610041China Department of Biochemistry and Molecular Biology Monash UniversityClaytonVIC 3800Australia Department of Biological Sciences Faculty of ScienceNational University of SingaporeSingapore 117543Republic of Singapore Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China Hospitaland West China School of Basic Medical Sciences&Forensic MedicineSichuan UniversityChengdu 610041China Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education Department of Reproductive MedicineWest China Second University Hospital of Sichuan UniversityChengduChina Department of Otorhinolaryngology and Head and Neck Surgery The Affiliated Lihuili HospitalNingbo University315040 NingboZhejiangChina

Osteoporosis,a metabolic bone disease characterized by low bone mineral density and deterioration of bone microarchitecture,has led to a high risk of fatal osteoporotic fractures worldwide.Accumulating evidence has revealed that sexual dimorphism is a notable feature of osteoporosis,with sex-specific differences in epidemiology and pathogenesis.Specifically,females are more susceptible than males to osteoporosis,while males are more prone to disability or death from the disease.To date,sex chromosome abnormalities and steroid hormones have been proven to contribute greatly to sexual dimorphism in osteoporosis by regulating the functions of bone cells.Understanding the sex-specific differences in osteoporosis and its related complications is essential for improving treatment strategies tailored to women and men.This literature review focuses on the mechanisms underlying sexual dimorphism in osteoporosis,mainly in a population of aging patients,chronic glucocorticoid administration,and diabetes.Moreover,we highlight the implications of sexual dimorphism for developing therapeutics and preventive strategies and screening approaches tailored to women and men.Additionally,the challenges in translating bench research to bedside treatments and future directions to overcome these obstacles will be discussed.

关键词： osteoporosis epidemiology overcome

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Overcoming cancer therapeutic bottleneck by drug repurposing

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1449-1473页

作者： Zhe Zhang Li Zhou Na Xie Edouard CNice Tao Zhang Yongping Cui Canhua Huang State Key Laboratory of Biotherapy and Cancer Center West China Hospitaland West China School of Basic Medical Sciences&Forensic MedicineSichuan Universityand Collaborative Innovation Center for Biotherapy610041 ChengduChina Department of Biochemistry and Molecular Biology Monash UniversityClaytonVICAustralia The School of Biological Science and Technology Chengdu Medical College610083 ChengduChina Department of Oncology The Second Affiliated Hospital of Chengdu Medical CollegeChina National Nuclear Corporation 416 HospitalChengdu610051 SichuanChina Cancer Institute Peking University Shenzhen HospitalShenzhen Peking University—the Hong Kong University of Science and Technology(PKU-HKUST)Medical Centerand Cancer InstituteShenzhen Bay Laboratory Shenzhen518035 ShenzhenChina Department of Pathology&Shanxi Key Laboratory of Carcinogenesis and Translational Research on Esophageal Cancer Shanxi Medical UniversityTaiyuan030001 ShanxiChina School of Basic Medical Sciences Chengdu University of Traditional Chinese MedicineChengdu611137 SichuanChina

Ever present hurdles for the discovery of new drugs for cancer therapy have necessitated the development of the alternative strategy of drug repurposing,the development of old drugs for new therapeutic purposes.This strategy with a cost-effective way offers a rare opportunity for the treatment of human neoplastic disease,facilitating rapid clinical translation.With an increased understanding of the hallmarks of cancer and the development of various data-driven approaches,drug repurposing further promotes the holistic productivity of drug discovery and reasonably focuses on target-defined antineoplastic compounds.The“treasure trove”of non-oncology drugs should not be ignored since they could target not only known but also hitherto unknown vulnerabilities of cancer.Indeed,different from targeted drugs,these old generic drugs,usually used in a multi-target strategy may bring benefit to patients.In this review,aiming to demonstrate the full potential of drug repurposing,we present various promising repurposed non-oncology drugs for clinical cancer management and classify these candidates into their proposed administration for either mono-or drug combination therapy.We also summarize approaches used for drug repurposing and discuss the main barriers to its uptake.

关键词： drugs therapeutic classify

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Emerging role of tumor cell plasticity in modifying therapeutic response

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Signal Transduction and Targeted Therapy 2020年第1期5卷 549-584页

作者： Siyuan Qin Jingwen Jiang Yi Lu Edouard CNice Canhua Huang Jian Zhang Weifeng He State Key Laboratory of Biotherapy and Cancer Center West China Hospitaland West China School of Basic Medical Sciences and Forensic MedicineSichuan Universityand Collaborative Innovation Center for Biotherapy610041 ChengduPeople’s Republic of China School of Medicine Southern University of Science and Technology ShenzhenShenzhenGuangdong 518055People’s Republic of China Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research ShenzhenGuangdongPeople’s Republic of China Department of Biochemistry and Molecular Biology Monash UniversityClaytonVICAustralia School of Basic Medical Sciences Chengdu University of Traditional Chinese Medicine1166 Liutai Road611137 ChengduPeople’s Republic of China State Key Laboratory of Trauma Burn and Combined InjuryInstitute of Burn ResearchSouthwest HospitalThird Military Medical University(Army Medical University)ChongqingPeople’s Republic of China Chongqing Key Laboratory for Disease Proteomics ChongqingPeople’s Republic of China

Resistance to cancer therapy is a major barrier to cancer management.Conventional views have proposed that acquisition of resistance may result from genetic mutations.However,accumulating evidence implicates a key role of non-mutational resistance mechanisms underlying drug tolerance,the latter of which is the focus that will be discussed here.Such non-mutational processes are largely driven by tumor cell plasticity,which renders tumor cells insusceptible to the drug-targeted pathway,thereby facilitating the tumor cell survival and growth.The concept of tumor cell plasticity highlights the significance of re-activation of developmental programs that are closely correlated with epithelial–mesenchymal transition,acquisition properties of cancer stem cells,and transdifferentiation potential during drug exposure.From observations in various cancers,this concept provides an opportunity for investigating the nature of anticancer drug resistance.Over the years,our understanding of the emerging role of phenotype switching in modifying therapeutic response has considerably increased.This expanded knowledge of tumor cell plasticity contributes to developing novel therapeutic strategies or combination therapy regimens using available anticancer drugs,which are likely to improve patient outcomes in clinical practice.

关键词： therapeutic plasticity thereby

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The pathogenesis and diagnosis of sepsis post burn injury

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Burns & Trauma 2021年第1期9卷 678-693页

作者： Pengju Zhang Bingwen Zou Yih-Cherng Liou Canhua Huang State Key Laboratory of Biotherapy and Cancer Center West China Hospitaland West China School of Basic Medical Sciences&Forensic MedicineSichuan Universityand Collaborative Innovation Center for BiotherapyNo.17 People’s South RoadChengdu610041China Department of Thoracic Oncology and Department of Radiation Oncology Cancer CenterWest China HospitalSichuan UniversityNo.37 Guoxue AlleyWuhou DistrictChengdu610041China Department of Biological Sciences Faculty of ScienceNational University of Singapore14 Science Drive 4117543Singapore

Burn is an under-appreciated trauma that is associated with unacceptably high morbidity and mortality.Although the survival rate after devastating burn injuries has continued to increase in previous decades due to medical advances in burn wound care,nutritional and fluid resuscitation and improved infection control practices,there are still large numbers of patients at a high risk of death.One of the most common complications of burn is sepsis,which is defined as“severe organ dysfunction attributed to host’s disordered response to infection”and is the primary cause of death in burn patients.Indeed,burn injuries are accompanied by a series of events that lead to sepsis and multiple organ dysfunction syndrome,such as a hypovolaemic state,immune and inflammatory responses and metabolic changes.Therefore,clear diagnostic criteria and predictive biomarkers are especially important in the prevention and treatment of sepsis and septic shock.In this review,we focus on the pathogenesis of burn wound infection and the post-burn events leading to sepsis.Moreover,the clinical and promising biomarkers of burn sepsis will also be summarized.

关键词： Burn Infection Sepsis Septic shock Multiple organ dysfunction syndrome Immune dysregulation Hypermetabolism Trauma Biomaker Inflammation

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From purines to purinergic signalling:molecular functions and human diseases

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Signal Transduction and Targeted Therapy 2021年第5期6卷 1463-1482页

作者： Zhao huang Na Xie Peter Illes Francesco Di Virgilio Henning Ulrich Alexey Semyanov Alexei Verkhratsky Beata Sperlagh Shu-Guang Yu Canhua Huang Yong Tang State Key Laboratory of Biotherapy and Cancer Center West China Hospitaland West China School of Basic Medical Sciences&Forensic MedicineSichuan Universityand Collaborative Innovation Center for BiotherapyChengduChina International Collaborative Centre on Big Science Plan for Purinergic Signalling Chengdu University of Traditional Chinese MedicineChengduChina Rudolf-Boehm-Institut für Pharmakologie und Toxikologie Universitaet LeipzigLeipzigGermany Department of Medical Sciences University of FerraraFerraraItaly Department of Biochemistry Institute of ChemistryUniversity of São PauloSão PauloBrazil Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of SciencesMoscowRussia Sechenov First Moscow State Medical University MoscowRussia Faculty of Biology Medicine and HealthThe University of ManchesterManchesterUK Department of Pharmacology Institute of Experimental MedicineHungarian Academy of SciencesBudapestHungary Acupuncture and Chronobiology Key Laboratory of Sichuan Province ChengduChina School of Basic Medical Sciences Chengdu University of Traditional Chinese MedicineChengduChina

Purines and their derivatives,most notably adenosine and ATP,are the key molecules controlling intracellular energy homoeostasis and nucleotide synthesis.Besides,these purines support,as chemical messengers,purinergic transmission throughout tissues and species.Purines act as endogenous ligands that bind to and activate plasmalemmal purinoceptors,which mediate extracellular communication referred to as“purinergic signalling”.Purinergic signalling is cross-linked with other transmitter networks to coordinate numerous aspects of cell behaviour such as proliferation,differentiation,migration,apoptosis and other physiological processes critical for the proper function of organisms.Pathological deregulation of purinergic signalling contributes to various diseases including neurodegeneration,rheumatic immune diseases,inflammation,and cancer.Particularly,gout is one of the most prevalent purine-related disease caused by purine metabolism disorder and consequent hyperuricemia.Compelling evidence indicates that purinoceptors are potential therapeutic targets,with specific purinergic agonists and antagonists demonstrating prominent therapeutic potential.Furthermore,dietary and herbal interventions help to restore and balance purine metabolism,thus addressing the importance of a healthy lifestyle in the prevention and relief of human disorders.Profound understanding of molecular mechanisms of purinergic signalling provides new and exciting insights into the treatment of human diseases.

关键词： metabolism diseases urine

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Managing the immune microenvironment of osteosarcoma:the outlook for osteosarcoma treatment

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Bone Research 2023年第1期11卷 21-46页

作者： Hailong Tian Jiangjun Cao Bowen Li Edouard CNice Haijiao Mao Yi Zhang Canhua Huang State Key Laboratory of Biotherapy and Cancer Center West China HospitalWest China School of Basic Medical Sciences&Forensic MedicineSichuan Universityand Collaborative Innovation Center for BiotherapyChengdu610041China Department of Biochemistry and Molecular Biology Monash UniversityClaytonVIC3800Australia Department of Orthopaedic Surgery The Affiliated Hospital of Medical SchoolNingbo UniversityNingboZhejiang315020People’s Republic of China Department of Orthopaedics The First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China

Osteosarcoma,with poor survival after metastasis,is considered the most common primary bone cancer in adolescents.Notwithstanding the efforts of researchers,its five-year survival rate has only shown limited improvement,suggesting that existing therapeutic strategies are insufficient to meet clinical needs.Notably,immunotherapy has shown certain advantages over traditional tumor treatments in inhibiting metastasis.Therefore,managing the immune microenvironment in osteosarcoma can provide novel and valuable insight into the multifaceted mechanisms underlying the heterogeneity and progression of the disease.Additionally,given the advances in nanomedicine,there exist many advanced nanoplatforms for enhanced osteosarcoma immunotherapy with satisfactory physiochemical characteristics.Here,we review the classification,characteristics,and functions of the key components of the immune microenvironment in osteosarcoma.This review also emphasizes the application,progress,and prospects of osteosarcoma immunotherapy and discusses several nanomedicine-based options to enhance the efficiency of osteosarcoma treatment.Furthermore,we examine the disadvantages of standard treatments and present future perspectives for osteosarcoma immunotherapy.

关键词： osteosarcoma metastasis treatment

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