BACKGROUND The treatment of gastric cancer(GC)has caused an enormous social burden worldwide.Accumulating studies have reported that N6-methyladenosine(m6A)is closely related to tumor progression.METTL5 is a m6A methy...BACKGROUND The treatment of gastric cancer(GC)has caused an enormous social burden worldwide.Accumulating studies have reported that N6-methyladenosine(m6A)is closely related to tumor progression.METTL5 is a m6A methyltransferase that plays a pivotal role in maintaining the metabolic stability of cells.However,its aberrant regulation in GC has not been fully elucidated.AIM To excavate the role of METTL5 in the development of GC.METHODS METTL5 expression and clinicopathological characteristics were analyzed via The Cancer Genome Atlas dataset and further verified via immunohistochemistry,western blotting and real-time quantitative polymerase chain reaction in tissue microarrays and clinical samples.The tumor-promoting effect of METTL5 on HGC-27 and AGS cells was explored in vitro by Cell Counting Kit-8 assays,colony formation assays,scratch healing assays,transwell assays and flow cytometry.The tumor-promoting role of METTL5 in vivo was evaluated in a xenograft tumor model.The EpiQuik m6A RNA Methylation Quantification Kit was used for m6A quantification.Next,liquid chromatography-mass spectrometry was used to evaluate the association between METTL5 and sphingomyelin metabolism,which was confirmed by Enzyme-linked immunosorbent assay and rescue tests.In addition,we investigated whether METTL5 affects the sensitivity of GC cells to cisplatin via colony formation and transwell experiments.RESULTS Our research revealed substantial upregulation of METTL5,which suggested a poor prognosis of GC patients.Increased METTL5 expression indicated distant lymph node metastasis,advanced cancer stage and pathological grade.An increased level of METTL5 correlated with a high degree of m6A methylation.METTL5 markedly promotes the proliferation,migration,and invasion of GC cells in vitro.METTL5 also promotes the growth of GC in animal models.METTL5 knockdown resulted in significant changes in sphingomyelin metabolism,which implies that METTL5 may impact the development of GC via sphingomyelin metabolism.In addition,high METTL5 expression led to cisplatin resistance.CONCLUSION METTL5 was found to be an oncogenic driver of GC and may be a new target for therapy since it facilitates GC carcinogenesis through sphingomyelin metabolism and cisplatin resistance.展开更多
Gastric cancer(GC)is a global health problem and a leading cause of cancerrelated deaths,with its mortality rate ranking third among all cancers.The etiology and progression of GC are characterized by a complex interp...Gastric cancer(GC)is a global health problem and a leading cause of cancerrelated deaths,with its mortality rate ranking third among all cancers.The etiology and progression of GC are characterized by a complex interplay of genetic and epigenetic changes,which present challenges for its early diagnosis and effective treatment.Elucidating the mechanisms underlying the occurrence and development of GC and identifying novel biomarkers for early detection and prognosis are crucial to improving patient outcomes.This editorial examines the role of methyltransferase-like 5(METTL5)in the progression of GC through sphingomyelin metabolism by considering an article published by Zhang et al in the World Journal of Gastrointestinal Oncology in 2024,which is entitled“METTL5 promotes GC progression via sphingomyelin metabolism”.These authors investigated the biological behavior of METTL5 in GC by examining its expression patterns,clinical relevance,functional effect,and potential mechanisms,as well as its response to chemotherapy.This editorial provides valuable insights into the role of METTL5 in the progression of GC and its potential as a therapeutic target.展开更多
支持等式测试的标识加密(identity-based encryption with equality test, IBEET)体制解决了传统等式测试方案中证书管理的问题,得到了广泛的关注.但现有的IBEET体制难以抵抗渗透攻击,且都是基于国外密码算法设计,不具有自主知识产权....支持等式测试的标识加密(identity-based encryption with equality test, IBEET)体制解决了传统等式测试方案中证书管理的问题,得到了广泛的关注.但现有的IBEET体制难以抵抗渗透攻击,且都是基于国外密码算法设计,不具有自主知识产权.基于此,提出一种支持等式测试并具有密码逆向防火墙的SM9标识加密方案(SM9 identity-based encryption scheme with equality test and cryptographic reverse firewalls, SM9-IBEET-CRF).该方案在用户与云服务器的上行信道间部署密码逆向防火墙(cryptographic reverse firewalls,CRF),对用户发出的信息执行重随机化以达到抵抗渗透攻击的作用.该方案拓展国密算法SM9至IBEET领域中,提升其运行效率并丰富国密算法在云计算领域的研究.给出了SM9-IBEET-CRF的形式化定义和安全模型,并在随机预言机模型中考虑2种不同的敌手将此方案在选择密文攻击下的不可区分性与单向性分别形式化地规约到BDH困难假设上.同时,该方案通过考虑第3种敌手证明CRF的部署为其带来维持功能性、保留安全性以及抵抗渗透性.实验仿真和分析结果展示了该方案的有效性.展开更多
针对属性基可搜索加密(ABSE)方案大都基于非国密算法设计,且无法抵抗内部算法替换攻击(ASA)的问题,提出一种支持密码逆向防火墙的基于SM9的属性基可搜索加密方案(SM9ABSE-CRF)。该方案将国密算法SM9扩展至ABSE领域,实现了细粒度数据访...针对属性基可搜索加密(ABSE)方案大都基于非国密算法设计,且无法抵抗内部算法替换攻击(ASA)的问题,提出一种支持密码逆向防火墙的基于SM9的属性基可搜索加密方案(SM9ABSE-CRF)。该方案将国密算法SM9扩展至ABSE领域,实现了细粒度数据访问控制,并引入密码逆向防火墙(CRF)技术有效抵御ASA。分析了SM9ABSE-CRF在判定性Diffie-Hellman(DBDH)假设下满足了选择关键词下的不可区分性,并形式化证明了CRF的部署满足维持功能性、保留安全性以及抵抗泄漏性。理论分析和仿真实验结果表明,与提供CRF的ABSE方案cABKSCRF(consistent Attribute-Based Keyword Search system with CRF)相比,SM9ABSE-CRF具有更高的安全性,并且在索引与陷门生成阶段也表现出显著的性能优势。展开更多
文摘BACKGROUND The treatment of gastric cancer(GC)has caused an enormous social burden worldwide.Accumulating studies have reported that N6-methyladenosine(m6A)is closely related to tumor progression.METTL5 is a m6A methyltransferase that plays a pivotal role in maintaining the metabolic stability of cells.However,its aberrant regulation in GC has not been fully elucidated.AIM To excavate the role of METTL5 in the development of GC.METHODS METTL5 expression and clinicopathological characteristics were analyzed via The Cancer Genome Atlas dataset and further verified via immunohistochemistry,western blotting and real-time quantitative polymerase chain reaction in tissue microarrays and clinical samples.The tumor-promoting effect of METTL5 on HGC-27 and AGS cells was explored in vitro by Cell Counting Kit-8 assays,colony formation assays,scratch healing assays,transwell assays and flow cytometry.The tumor-promoting role of METTL5 in vivo was evaluated in a xenograft tumor model.The EpiQuik m6A RNA Methylation Quantification Kit was used for m6A quantification.Next,liquid chromatography-mass spectrometry was used to evaluate the association between METTL5 and sphingomyelin metabolism,which was confirmed by Enzyme-linked immunosorbent assay and rescue tests.In addition,we investigated whether METTL5 affects the sensitivity of GC cells to cisplatin via colony formation and transwell experiments.RESULTS Our research revealed substantial upregulation of METTL5,which suggested a poor prognosis of GC patients.Increased METTL5 expression indicated distant lymph node metastasis,advanced cancer stage and pathological grade.An increased level of METTL5 correlated with a high degree of m6A methylation.METTL5 markedly promotes the proliferation,migration,and invasion of GC cells in vitro.METTL5 also promotes the growth of GC in animal models.METTL5 knockdown resulted in significant changes in sphingomyelin metabolism,which implies that METTL5 may impact the development of GC via sphingomyelin metabolism.In addition,high METTL5 expression led to cisplatin resistance.CONCLUSION METTL5 was found to be an oncogenic driver of GC and may be a new target for therapy since it facilitates GC carcinogenesis through sphingomyelin metabolism and cisplatin resistance.
基金Supported by Jiangsu Commission of Health,No.LKZ2023012Social Development Project of Zhenjiang City,No.SS2023011.
文摘Gastric cancer(GC)is a global health problem and a leading cause of cancerrelated deaths,with its mortality rate ranking third among all cancers.The etiology and progression of GC are characterized by a complex interplay of genetic and epigenetic changes,which present challenges for its early diagnosis and effective treatment.Elucidating the mechanisms underlying the occurrence and development of GC and identifying novel biomarkers for early detection and prognosis are crucial to improving patient outcomes.This editorial examines the role of methyltransferase-like 5(METTL5)in the progression of GC through sphingomyelin metabolism by considering an article published by Zhang et al in the World Journal of Gastrointestinal Oncology in 2024,which is entitled“METTL5 promotes GC progression via sphingomyelin metabolism”.These authors investigated the biological behavior of METTL5 in GC by examining its expression patterns,clinical relevance,functional effect,and potential mechanisms,as well as its response to chemotherapy.This editorial provides valuable insights into the role of METTL5 in the progression of GC and its potential as a therapeutic target.
文摘支持等式测试的标识加密(identity-based encryption with equality test, IBEET)体制解决了传统等式测试方案中证书管理的问题,得到了广泛的关注.但现有的IBEET体制难以抵抗渗透攻击,且都是基于国外密码算法设计,不具有自主知识产权.基于此,提出一种支持等式测试并具有密码逆向防火墙的SM9标识加密方案(SM9 identity-based encryption scheme with equality test and cryptographic reverse firewalls, SM9-IBEET-CRF).该方案在用户与云服务器的上行信道间部署密码逆向防火墙(cryptographic reverse firewalls,CRF),对用户发出的信息执行重随机化以达到抵抗渗透攻击的作用.该方案拓展国密算法SM9至IBEET领域中,提升其运行效率并丰富国密算法在云计算领域的研究.给出了SM9-IBEET-CRF的形式化定义和安全模型,并在随机预言机模型中考虑2种不同的敌手将此方案在选择密文攻击下的不可区分性与单向性分别形式化地规约到BDH困难假设上.同时,该方案通过考虑第3种敌手证明CRF的部署为其带来维持功能性、保留安全性以及抵抗渗透性.实验仿真和分析结果展示了该方案的有效性.
文摘针对属性基可搜索加密(ABSE)方案大都基于非国密算法设计,且无法抵抗内部算法替换攻击(ASA)的问题,提出一种支持密码逆向防火墙的基于SM9的属性基可搜索加密方案(SM9ABSE-CRF)。该方案将国密算法SM9扩展至ABSE领域,实现了细粒度数据访问控制,并引入密码逆向防火墙(CRF)技术有效抵御ASA。分析了SM9ABSE-CRF在判定性Diffie-Hellman(DBDH)假设下满足了选择关键词下的不可区分性,并形式化证明了CRF的部署满足维持功能性、保留安全性以及抵抗泄漏性。理论分析和仿真实验结果表明,与提供CRF的ABSE方案cABKSCRF(consistent Attribute-Based Keyword Search system with CRF)相比,SM9ABSE-CRF具有更高的安全性,并且在索引与陷门生成阶段也表现出显著的性能优势。
