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Ferroptosis:a critical mechanism of N^(6)-methyladenosine modification involved in carcinogenesis and tumor progression

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Science China(Life Sciences) 2024年第6期67卷 1119-1132页

作者： Qingqing Wei Changning Xue Mengna Li Jianxia Wei Lemei Zheng Shipeng Chen Yumei Duan Hongyu Deng Faqing Tang Wei Xiong Ming Zhou NHC key laboratory of Carcinogenesis Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410013China cancer Research Institute and School of Basic Medical Sciences Central South UniversityChangsha 410078China The key laboratory of Carcinogenesis and cancer Invasion of the Chinese Ministry of Education Central South UniversityChangsha 410078China hunan key laboratory of Oncotarget Gene Hunan Key Laboratory of Cancer MetabolismHunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410013China

Ferroptosis is an iron-dependent regulatory cell necrosis induced by iron overload and lipid *** occurs when multiple redoxactive enzymes are ectopically expressed or show abnormal ***,the precise regulation of ferroptosis-related molecules is mediated across multiple levels,including transcriptional,posttranscriptional,translational,and epigenetic levels.N^(6)-methyladenosine(m^(6)A)is a highly evolutionarily conserved epigenetic modification in *** m^(6)A modification is commonly linked to tumor proliferation,progression,and therapy resistance because it is involved in RNA metabolic ***,accumulating evidence suggests that dysregulated ferroptosis caused by the m^(6)A modification drives tumor *** this review,we summarized the roles of m^(6)A regulators in ferroptosis-mediated malignant tumor progression and outlined the m^(6)A regulatory mechanism involved in ferroptosis *** also analyzed the potential value and application strategies of targeting m^(6)A/ferroptosis pathway in the clinical diagnosis and therapy of tumors.

关键词： ferroptosis m6A modification RNA methylation m^(6)A regulator tumor progression

Chronic stress as an emerging risk factor for the development and progression of glioma

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Chinese Medical Journal 2024年第4期137卷 394-407页

作者： Lan Yi Xiang Lin Xiaoling She Wei Gao Minghua Wu Institute of Cytology and Genetics The Hengyang Key Laboratory of Cellular Stress BiologyHunan Province Cooperative Innovation Center for Molecular Target New Drug StudyHengyang Medical SchoolUniversity of South ChinaHengyangHunan 421001China Department of Pathology The Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China key laboratory of Carcinogenesis and cancer Invasion of Ministry of Education Cancer Research InstituteCentral South UniversityChangshaHunan 410008China NHC key laboratory of Carcinogenesis Xiangya HospitalCentral South UniversityChangshaHunan 410008China

Gliomas tend to have a poor prognosis and are the most common primary malignant tumors of the central nervous *** with patients with other cancers,glioma patients often suffer from increased levels of psychological stress,such as anxiety and *** stress(CS)is thought to impact glioma ***,because of the complex mechanisms underlying CS and variability in individual tolerance,the role of CS in glioma remains *** review suggests a new proposal to redivide the stress system into two *** activity is dominant ***-signaling molecules produced by the neuroendocrine system are dominant *** discuss the underlying molecular mechanisms by which CS impacts *** pharmacological treatments are also summarized from the therapeutic perspective of CS.

关键词： Chronic stress Glioma Microbiota-gut-brain axis Neuroendocrine system Stress system Neural circuit

Ferroptosis: a critical mechanism of N-methyladenosine modification involved in carcinogenesis and tumor progression

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Science China Life Sciences 2024年

作者： Qingqing Wei Changning Xue Mengna Li Jianxia Wei Lemei Zheng Shipeng Chen Yumei Duan Hongyu Deng Faqing Tang Wei Xiong Ming Zhou NHC key laboratory of Carcinogenesis Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine Central South University cancer Research Institute and School of Basic Medical Sciences Central South University The key laboratory of Carcinogenesis and cancer Invasion of the Chinese Ministry of Education Central South University hunan key laboratory of Oncotarget Gene Hunan Key Laboratory of Cancer Metabolism Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine Central South University

Ferroptosis is an iron-dependent regulatory cell necrosis induced by iron overload and lipid peroxidation. It occurs when multiple redoxactive enzymes are ectopically expressed or show abnormal function. Hence, the precise regulation of ferroptosis-related molecules is mediated across multiple levels, including transcriptional, posttranscriptional, translational, and epigenetic levels. N6-methyladenosine(m6A) is a highly evolutionarily conserved epigenetic modification in mammals. The m6A modification is commonly linked to tumor proliferation, progression, and therapy resistance because it is involved in RNA metabolic processes. Intriguingly, accumulating evidence suggests that dysregulated ferroptosis caused by the m6A modification drives tumor development. In this review, we summarized the roles of m6A regulators in ferroptosis-mediated malignant tumor progression and outlined the m6A regulatory mechanism involved in ferroptosis pathways. We also analyzed the potential value and application strategies of targeting m6A/ferroptosis pathway in the clinical diagnosis and therapy of tumors.

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Cellular metabolism: A key player in cancer ferroptosis

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cancer Communications 2024年第2期44卷 185-204页

作者： Xianjie Jiang Qiu Peng Mingjing Peng Linda Oyang Honghan Wang Qiang Liu Xuemeng Xu Nayiyuan Wu Shiming Tan Wenjuan Yang Yaqian Han Jinguan Lin Longzheng Xia Yanyan Tang Xia Luo Jie Dai Yujuan Zhou Qianjin Liao hunan key laboratory of cancer Metabolism Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangshaHunanP.R.China Public Service Platform of Tumor Organoids Technology ChangshaHunanP.R.China Department of Head and Neck Surgery Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangshaHunanP.R.China Hengyang Medical School University of South ChinaHengyangHunanP.R.China

Cellular metabolism is the fundamental process by which cells maintain growth and *** produces energy,furnishes raw materials,and intermedi-ates for biomolecule synthesis,and modulates enzyme activity to sustain normal cellular *** metabolism is the foundation of cellular life processes and plays a regulatory role in various biological functions,including pro-grammed cell *** is a recently discovered form of iron-dependent programmed cell *** inhibition of ferroptosis plays a crucial role in tumorigenesis and tumor ***,the role of cellular metabolism,particularly glucose and amino acid metabolism,in cancer ferroptosis is not well ***,we reviewed glucose,lipid,amino acid,iron and sele-nium metabolism involvement in cancer cell ferroptosis to elucidate the impact of different metabolic pathways on this ***,we provided a detailed overview of agents used to induce cancer *** explained that the metabolism of tumor cells plays a crucial role in maintaining intracellu-lar redox homeostasis and that disrupting the normal metabolic processes in these cells renders them more susceptible to iron-induced cell death,resulting in enhanced tumor cell *** combination of ferroptosis inducers and cel-lular metabolism inhibitors may be a novel approach to future cancer therapy and an important strategy to advance the development of treatments.

关键词： cancer therapy cellular metabolism ferroptosis inducer ferroptosis

Automated screening of primary cell-based aptamers for targeting and therapy of pancreatic cancer

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Chinese Chemical Letters 2024年第2期35卷 300-304页

作者： Zhukang Guo Baijiang Jin Yile Fang Lian Jin Song Li Yan Deng Zhu Chen Hui Chen Yuanying Zhang Rabia Usman nongyue He State key laboratory of Digital Medical Engineering School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China hunan key laboratory of Biomedical Nanomaterials and Devices Hunan University of TechnologyZhuzhou 412007China Department of Molecular Biology Jiangsu Cancer HospitalNanjing 210009China

Although it has been developed for many years, nucleic acid aptamer screening technology still fails to be widely used, a considerable part of it is due to the variability of tumor cell morphology, which leads to the use of immortalized cell lines in the laboratory to screen nucleic acid aptamers for recognition ability of tumor cells in the diseased *** address this, primary cells that can be stably passaged were isolated and extracted from spontaneous tumors of genetically engineered pancreatic ductal adenocarcinoma model mice in this ***, an automated screening instrument for nucleic acid aptamers developed autonomously by our group was used to perform efficient aptamer screening using a limited number of cells, and the obtained nucleic acid aptamers were affinity verified at the cellular ***, to answer the question of the cell growth environment difference on the recognition ability of nucleic acid aptamers, we verified its targeting ability to tumors in vivo on a nude mice xenograft tumor model, and further used a common antitumor drug doxorubicin combined with nucleic acid aptamers to verify the drug loading ability of this aptamer combined with the targeting therapeutic ability.

关键词： Aptamer Cell-SELEX Automatic instrument Combination therapy Pancreatic cancer

Expression of cyclin-dependent kinase 9 is positively correlated with the autophagy level in colon cancer

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 314-330页

作者： Lei Zheng Jia Lu Da-Lu Kong Department of Colorectal cancer Surgery National Clinical Research Center for CancerKey Laboratory of Cancer Immunology and Biotherapy of TianjinTianjin Key Laboratory of Digestive CancerKey Laboratory of Cancer Prevention and Therapy of TianjinTianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and HospitalTianjin 300060China Department of Infection Management National Clinical Research Center for CancerKey Laboratory of Cancer Immunology and Biotherapy of TianjinTianjin Key Laboratory of Digestive CancerKey Laboratory of Cancer Prevention and Therapy of TianjinTianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and HospitalTianjin 300060China

BACKGROUND Cyclin-dependent kinase 9(CDK9)expression and autophagy in colorectal cancer(CRC)tissues has not been widely ***9,a key regulator of transcription,may influence the occurrence and progression of *** expression of auto-phagy-related genes BECN1 and drug resistance factor ABCG2 may also play a role in *** normal physiological conditions,autophagy can inhibit tumorigenesis,but once a tumor forms,autophagy may promote tumor ***,understanding the relationship between autophagy and cancer,partic-ularly how autophagy promotes tumor growth after its formation,is a key motivation for this *** To investigate the relationship between CDK9 expression and autophagy in CRC,assess differences in autophagy between left and right colon cancer,and analyze the associations of autophagy-related genes with clinical features and *** We collected tumor tissues and paracarcinoma tissues from colon cancer patients with liver metastasis to observe the level of autophagy in tissues with high levels of CDK9 and low levels of *** also collected primary tissue from left and right colon cancer patients with liver metastasis to compare the autophagy levels and the expression of BECN1 and ABCG2 in the tumor and paracarcinoma *** The incidence of autophagy and the expression of BECN1 and ABCG2 were different in left and right colon cancer,and autophagy might be involved in the occurrence of chemotherapy *** analysis of the rela-tionship between the expression of autophagy-related genes CDK9,ABCG2,and BECN1 and the clinical features and prognosis of colorectal cancer showed that the high expression of CDK9 indicated a poor prognosis in colorectal *** This study laid the foundation for further research on the combination of CDK9 inhibitors and autophagy inhibitors in the treatment of patients with CRC.

关键词： Autophagy Tumorigenesis Tumor tissue Paracarcinoma tissue Expression Left/right colon cancer

Role of adhesion molecules in cancer and targeted therapy

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Science China(Life Sciences) 2024年第5期67卷 940-957页

作者： Chunmei Fan Fang Xiong Shanshan Zhang Zhaojian Gong Qianjin Liao Guiyuan Li Can Guo Wei Xiong He Huang Zhaoyang Zeng NHC key laboratory of Carcinogenesis and hunan key laboratory of cancer Metabolism Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410000China Department of Histology and Embryology Xiangya School of MedicineCentral South UniversityChangsha410013China Department of Stomatology Xiangya HospitalCentral South UniversityChangsha 410078China Department of Oral and Maxillofacial Surgery The Second Xiangya HospitalCentral South UniversityChangsha 410011China key laboratory of Carcinogenesis and cancer Invasion of the Chinese Ministry of Education Cancer Research InstituteCentral South UniversityChangsha 410078China

Adhesion molecules mediate cell-to-cell and cell-to-extracellular matrix interactions and transmit mechanical and chemical signals among *** mechanisms deregulate adhesion molecules in cancer,enabling tumor cells to proliferate without restraint,invade through tissue boundaries,escape from immune surveillance,and survive in the tumor *** studies have revealed that adhesion molecules also drive angiogenesis,reshape metabolism,and are involved in stem cell *** this review,we summarize the functions and mechanisms of adhesion molecules in cancer and the tumor microenvironment,as well as the therapeutic strategies targeting adhesion *** studies have implications for furthering our understanding of adhesion molecules in cancer and providing a paradigm for exploring novel therapeutic approaches.

关键词： adhesion molecules tumor microenvironment invasion and metastasis reshaping metabolism angiogenesis immune evasion tumor stemness therapeutic strategy

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CD147 Facilitates the Pathogenesis of Psoriasis through Glycolysis and H3K9me3 Modification in Keratinocytes

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Research 2024年第1期2023卷 509-523页

作者： Chao Chen Xiaoqing Yi Panpan Liu Jie Li Bei Yan Detian Zhang Lei Zhu Pian Yu Lei Li Jiaxiong Zhang Yehong Kuang Shuang Zhao Wu Zhu Cong Peng Xiang Chen Department of Dermatology Xiangya HospitalCentral South UniversityChangshaHunanChina National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology ChangshaHunanChina Furong laboratory ChangshaHunanChina hunan key laboratory of Skin cancer and Psoriasis Hunan Engineering Research Center of Skin Health and DiseaseXiangya HospitalCentral South UniversityChangshaHunanChina National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunanChina

Psoriasis is a chronic inflammatory skin disease featuring rapid proliferation of epidermal *** elevated glycolysis flux has been reported in psoriasis,the molecular mechanisms underlying its pathogenesis remain *** investigated the role of the integral membrane protein CD147 in psoriasis pathogenesis,observing its high expression in psoriatic skin lesions of humans and imiquimod(IMQ)-induced mouse *** mouse models,genomic deletion of epidermal CD147 markedly attenuated IMQ-induced psoriatic *** found that CD147 interacted with glucose transporter 1(Glut1).Depletion of CD147 in the epidermis blocked glucose uptake and glycolysis in vitro and in *** CD147-knockout mice and keratinocytes,oxidative phosphorylation was increased in the epidermis,indicating CD147's pivotal role in glycolysis reprogramming during pathogenesis of *** non-targeted and targeted metabolic techniques,we found that epidermal deletion of CD147 significantly increased the production of carnitine and α-ketoglutaric acid(α-KG).

关键词： CD147 pathogenesis markedly

Self-assembled amphiphilic NIR-Ⅱ emissive nano-micelles for imaging-guided photothermal therapy of colorectal cancer

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Science China Chemistry 2024年第8期67卷 2767-2774页

作者： Axin He Fangfang Xia Da Han Qinglai Yang Weihong Tan Institute of Molecular Medicine(IMM) Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200240China Center for Molecular Imaging Probe Hunan Province Key Laboratory of Cancer Cellular and Molecular PathologyCancer Research InstituteHengyang Medical SchoolUniversity of South ChinaHengyang 421001China The key laboratory of Zhejiang Province for Aptamers and Theranostics Zhejiang Cancer Hospital Hangzhou Institute of Medicine(HIM)Chinese Academy of SciencesHangzhou 310022China Molecular Science and Biomedicine laboratory(MBL) State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringCollege of BiologyAptamer Engineering Center of Hunan ProvinceHunan UniversityChangsha 410082China

Colorectal cancer(CRC) is one of the major causes of cancer-related mortality worldwide. Most near-infrared(NIR) agents used in clinical CRC treatment are at NIR-I(700–900 nm) window, which has limitations on deep tissue, and fluorescent probes in the second NIR(1,000–1,700 nm) allow high-resolution bioimaging with deep tissue penetration. However, existing NIR-II fluorophores used in clinical are still rare. Herein, based on shielding-donor-acceptor-donor-shielding(S-D-A-D-S) scaffold, we developed an organic small-molecule fluorophore IR-BTGP with NIR-II emission for imaging-guided photothermal therapy(PTT) in CRC mice model. Amphiphilic IR-BTGP can be self-assembled into spherical nano-micelles, which presents reliable water solubility and photothermal conversion efficiency(30.2%). In vitro experiments indicate that cancer cells treated with IRBTGP were significantly killed upon 808 nm light irradiation. Furthermore, in vivo NIR-II fluorescence imaging confirms that IR-BTGP accumulates in the tumor region. Remarkably, a significant tumor inhibition rate(78.5%) was observed in tumorbearing mice when treated with IR-BTGP plus 808 nm irradiation. Therefore, this work shows that IR-BTGP holds great promise as an NIR-II fluorescence imaging-guided PTT platform for CRC in the future.

关键词： photothermal therapy(PTT) second near-infrared(NIR-Ⅱ)imaging organic molecule