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RP11-789C1.1 inhibits gastric cancer cell proliferation and accelerates apoptosis via the atr/CHK1 signaling pathway

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中华医学杂志(英文版) 2024年第15期137卷 1835-1843页

作者： Liu Wenwei Feng Wei Zhang Yongxin Lei Tianxiang Wang Xiaofeng Qiao Tang Chen Zehong Song Wu Digestive Diseases Center The Seventh Affiliated Hospital of Sun Yat-sen University Shenzhen Guangdong China Department of Gastrointestinal Surgery The First Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong China Laboratory of General Surgery The First Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong China Department of Gastrointestinal Surgery The Third Affiliated Hospital of Sun Yat-sen University Guangzhou Guangdong China

Background: Long non-coding RNAs (lncRNAs) plays an important role in the progression of gastric cancer (GC). Their involvement ranges from genetic regulation to cancer progression. However, the mechanistic roles of RP11-789C1.1 in GC are not fully ***: We identified the expression of lncRNA RP11-789C1.1 in GC tissues and cell lines by real-time fluorescent quantitative polymerase chain reaction. A series of functional experiments revealed the effect of RP11-789C1.1 on the proliferation of GC *** vivo experiments verified the effect of RP11-789C1.1 on the biological behavior of a GC cell line. RNA pull-down unveiled RP11-789C1.1 interacting proteins. Western blot analysis indicated the downstream pathway changes of RP11-789C1.1, and an oxaliplatin dosing experiment disclosed the influence of RP11-789C1.1 on the drug sensitivity of ***: Our results demonstrated that RP11-789C1.1 inhibited the proliferation of GC cells and promoted the apoptosis of GC cells. Mechanistically, RP11-789C1.1 inhibited checkpoint kinase 1 (CHK1) phosphorylation by binding ataxiatelangiectasia mutated and Rad3 related (atr), a serine/threonine-specific protein kinase, promoted GC apoptosis, and mediated oxaliplatin ***: In general, we discovered a tumor suppressor molecule RP11-789C1.1 and confirmed its mechanism of action, providing a theoretical basis for targeted GC therapy.

关键词： Long non-coding RNA RP11-789C1.1 Stomach neoplasms atr CHK1 Oxaliplatin

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LncRNA HOTAIR promotes DNA damage repair and radioresistance by targeting atr in colorectal cancer

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Oncology Research 2024年第8期32卷 1335-1346页

作者： HAIQING HU HAO YANG SHUAISHUAI FAN XUE JIA YING ZHAO HONGRUI LI Department of Endoscopic Center Peking University Cancer Hospital(Inner Mongolia Campus)&Affiliated Cancer Hospital of Inner Mongolia Medical UniversityHuhhot010020China Department of Radiation Oncology Peking University Cancer Hospital(Inner Mongolia Campus)&Affiliated Cancer Hospital of Inner Mongolia Medical UniversityKey Laboratory of Radiation Physics and Biology of Inner Mongolia Medical UniversityPeking University Cancer Hospital(Inner Mongolia Campus)&Affiliated Cancer Hospital of Inner Mongolia Medical UniversityHuhhot010020China Graduate School Inner Mongolia Medical UniversityHuhhot010020China

Long non-coding RNAs(lncRNAs)have been implicated in cancer progression and drug resistance ***,there is evidence that lncRNA HOX transcript antisense intergenic RNA(HOTAIR)is involved in colorectal cancer(CRC)*** present study aimed to examine the functional role of lncRNA HOTAIR in conferring radiotherapy resistance in CRC cells,as well as the underlying *** relative expression levels of HOTAIR were examined in 70 pairs of CRC tumor and para-cancerous tissues,as well as in radiosensitive and radioresistant *** correlations between HOTAIR expression levels and clinical features of patients with CRC were assessed using the Chi-square *** assays such as cell proliferation,colony formation and apoptosis assays were conducted to determine the radiosensitivity in CRC cells with HOTAIR silencing after treatment with different doses of *** pull-down assay andﬂuorescence in situ hybridization(FISH)were used to determine the interaction between HOTAIR and DNA damage response mediator ataxia-telangiectasia mutated-and Rad3-related(atr).HOTAIR was signiﬁcantly upregulated in CRC tumor tissues,especially in radioresistant tumor *** elevated expression of HOTAIR was correlated with more advanced histological grades,distance metastasis and the poor prognosis in patients with *** HOTAIR suppressed the proliferation and promoted apoptosis and radiosensitivity in CRC *** knockdown also inhibited the tumorigenesis of CRC cells and enhanced the sensitivity to radiotherapy in a mouse xenograft ***,the data showed that HOTAIR could interact with atr to regulate the DNA damage repair signaling *** HOTAIR impaired the atr-atr interacting protein(atrIP)complex and signaling in cell cycle ***,the present results indicate that lncRNA HOTAIR facilitates the DNA damage response pathway and promotes radioresistance in CRC cells by targeting atr.

关键词： LncRNA HOTAIR CRC radioresistance DNA damage repair atr

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测量机器人atr自动照准技术在变形监测中的应用分析

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测绘与空间地理信息 2024年第8期47卷 195-198页

作者：陈海俊重庆市勘测院重庆401142

通过对基坑监测常用的极坐标法误差因素进行分析,同时对测量机器人atr测量模式观测数据精度进行统计,与人工手动照准测量模式进行对比,验证了测量机器人atr测量模式在基坑位移变形监测中的可行性及可靠性。同时采用SOKKIA NET05AXII测... 详细信息

通过对基坑监测常用的极坐标法误差因素进行分析,同时对测量机器人atr测量模式观测数据精度进行统计,与人工手动照准测量模式进行对比,验证了测量机器人atr测量模式在基坑位移变形监测中的可行性及可靠性。同时采用SOKKIA NET05AXII测量机器人对某商贸中心基坑施工项目进行位移监测,与传统人工手动照准测量模式监测数据基本一致,且测量机器人atr测量模式作业效率相对更高,同时在远距离监测条件下,测量机器人atr自动照准测量精度相对更高,能够为基坑施工提供较为准确可靠的变形监测数据。

关键词：测量机器人 atr 极坐标法变形监测

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Chemical screen identifies shikonin as a broad DNA damage response inhibitor that enhances chemotherapy through inhibiting ATM and atr

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Acta Pharmaceutica Sinica B 2022年第3期12卷 1339-1350页

作者： Fangfang Wang Sora Jin Franklin Mayca Pozo Danmei Tian Xiyang Tang Yi Dai Xinsheng Yao Jinshan Tang Youwei Zhang Institute of Traditional Chinese Medicine and Natural Products College of PharmacyJinan UniversityGuangzhou 510632China Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drug Research Jinan UniversityGuangzhou 510632China Department of Pharmacology Case Comprehensive Cancer CenterCase Western Reserve University School of MedicineClevelandOH 44106USA

DNA damage response(DDR)is a highly conserved genome surveillance mechanism that preserves cell viability in the presence of chemotherapeutic ***,small molecules that inhibit DDR are expected to enhance the anti-cancer effect of *** a recent chemical library screen,we identified shikonin as an inhibitor that strongly suppressed DDR activated by various chemotherapeutic drugs in cancer cell lines derived from different ***,shikonin inhibited the activation of ataxia telangiectasia mutated(ATM),and to a lesser degree ATM and RAD3-related(atr),two master upstream regulators of the DDR signal,through inducing degradation of ATM and atr-interacting protein(atrIP),an obligate associating protein of atr,*** a result of DDR inhibition,shikonin enhanced the anti-cancer effect of chemotherapeutic drugs in both cell cultures and in mouse *** degradation of atrIP is proteasome dependent,that of ATM depends on caspase-and lysosome-,but not *** of ATM significantly mitigated DDR inhibition and cell death induced by shikonin and chemotherapeutic *** novel findings reveal shikonin as a pan DDR inhibitor and identify ATM as a primary factor in determining the chemo sensitizing effect of *** data may facilitate the development of shikonin and its derivatives as potential chemotherapy sensitizers through inducing ATM degradation.

关键词： Chemical screen Shikonin DNA damage Response ATM atr atrIP Protein degradation Chemo sensitizing

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NUSAP1 potentiates chemoresistance in glioblastoma through its SAP domain to stabilize atr

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Signal Transduction and Targeted Therapy 2020年第1期5卷 2019-2029页

作者： Yuzu Zhao Jiang He Yongsen Li Shengqing Lv Hongjuan Cui State Key Laboratory of Silkworm Genome Biology Southwest UniversityChongqingChina Cancer Center Medical Research InstituteSouthwest UniversityChongqingChina Department of Neurosurgery Xinqiao HospitalThird Military Medical UniversityChongqingChina

NUSAP1,which is a microtubule-associated protein involved in mitosis,plays essential roles in diverse biological processes,especially in cancer *** this study,NUSAP1 was found to be overexpressed in GBM tissues in a grade-dependent manner compared with normal brain ***1 was also highly expressed in GBM patients,dead patients,and GBM *** addition,NUSAP1 was found to participate in cell proliferation,apoptosis,and DNA damage in GBM *** telangiectasia and Rad3-related protein(atr)are a primary sensor of DNA damage,and atr is also a promising target in cancer ***,we found that NUSAP1 positively regulated the expression of ***,NUSAP1 suppressed the ubiquitin-dependent proteolysis of *** SAP(SAF-A/B,Acinus,and PIAS)domain is a common motif of many SUMO(small ubiquitin-like modifier)E3 ligases,and this domain is involved in substrate recognition and ligase *** study further demonstrated that the SAP domain of NUSAP1 promoted the sumoylation of atr,and thereby antagonized the ubiquitination of *** results suggest that NUSAP1 stabilizes atr by ***,NUSAP1 potentiated chemotherapeutic resistance to temozolomide(TMZ)and doxorubicin(DOX)through its SAP ***,this study indicates that NUSAP1 is a promising therapeutic target in GBM.

关键词： AP1 damage atr

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Band Selection Method of Absorption Peak Perturbance for the FTIR/atr SpectrumAnalysis

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Computers, Materials & Continua 2018年第11期57卷 261-268页

作者： Jun Xie Chong Wang Jiaxiang Cai Fuhong Cai The Mechanical and Electrical Engineering College Hainan UniversityHaikouHainan570228China Department of Industrial Systems Engineering&Management National University of SingaporeSingapore

The rapid quantification method of human serum glucose was established by using the Fourier transform infrared spectroscopy(FTIR)and attenuated total reflection(atr).By the subtracted spectra between glucose aqueous solution and de-ionized water,absorption peaks are calculated in fingerprint *** on these absorption peaks and multiple linear regression(MLR)model,discrete band selection method of absorption peaks disturbance model(APDM)was developed.5 absorption peaks 1150 cm^-1,1103 cm^-1,1078 cm^-1,1034 cm^-1,991 cm^-1 were found in fingerprint *** these absorption peaks to establish absorption peaks disturbance model,the optimal wavelength combinations are 1140 cm^-1,1096 cm^-1,1084 cm^-1,1030 cm^-1,993 cm^-1,the corresponding C-RMSEP and C-RP are 1.164 mmol/L and 0.828 *** results show that the optimal prediction effect of APDM was obviously better than the one of the Partial least squares(PLS)model,and the complexity of the optimal model is reduced greatly *** results also provide a theoretical basis for design of small and portable human serum glucose spectrometer.

关键词： Band selection FTIR atr serum glucose

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Non-canonical role of the atr pathway in axon regeneration as a mechanosensitive brake

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Neural Regeneration Research 2022年第11期17卷 2423-2424页

作者： Feng Li Yuanquan Song Institute for Translational Brain Research Fudan UniversityShanghaiChina Raymond G.Perelman Center for Cellular and Molecular Therapeutics The Children’s Hospital of Philadelphiaand Department of Pathology and Laboratory MedicineUniversity of PennsylvaniaPhiladelphiaPAUSA

DNA damage has been linked to *** DNA damage response(DDR)pathways help preserve DNA integrity in the nervous system during both the developmental and mature *** of factors in various signaling pathways responsive to different types of DNA damage have been associated with developmental syndromes with neurological symptoms(McKinnon,2009;Araújo and Kuraoka,2019;Khokhlova et al.,2020).

关键词： damage atr DDR

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Modulation of fatty acid synthase by atr checkpoint kinase Rad3

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Journal of Molecular Cell Biology 2019年第12期11卷 1098-1100页

作者： Shuwan Qiu Sheng Liu Zannati Ferdous Zaoti Xuejuan Wang and Gang Cai First Affiliated Hospital of USTC School of Life SciencesHefei National Laboratory for Physical Sciences at MicroscaleUniversity of Science and Technology of ChinaHefei 230027China CAS Center for Excellence in Molecular Cell Science Chinese Academy of SciencesHefei 230026China.

Fatty acid synthase (FAS) is the key enzyme for de novo fatty acid synthesis and exists widely from bacteria to mammalian cells (Schweizer and Hofmann, 2004). It is involved in membrane organization, metabolism regulation, energy storage, and many other processes (Maier et al., 2010). The ataxia telangiectasia-mutated and Rad3-related kinase (atr) is a master regulator of DNA damage response (DDR) and is highly conserved. atr is activated by DNA double-strand breaks and various types of DNA replication stresses (Cortez et al., 2001). Recent researches have reported that FAS seems closely related to genome stability (Wu et al., 2016). It has been proved that palmitic acid, the product of FAS, can inhibit atr phosphorylation and kinase activity in mouse fibroblast (Zeng et al., 2008). These studies suggest that there is a crosstalk between fatty acid metabolism and DDR pathway, but the mechanism remains unknown.

关键词： atr DDR metabolism

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一种在线监测的atr探头的设计

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光谱学与光谱分析 2016年第6期36卷 1954-1958页

作者：石磊刘佳郜武张倩暄王巍北京雪迪龙科技股份有限公司北京102206 北京航天控制仪器研究所北京100854

生物过程是一个复杂的系统,在反应过程中,会产生固态、液态、气态的过程反应物,且具有生物活性,想要准确的掌握过程反应物的种类与含量,必须对生物过程进行实时在线的监测,才能够获得准确的数据。生物过程的原位在线分析依赖于高性能的... 详细信息

生物过程是一个复杂的系统,在反应过程中,会产生固态、液态、气态的过程反应物,且具有生物活性,想要准确的掌握过程反应物的种类与含量,必须对生物过程进行实时在线的监测,才能够获得准确的数据。生物过程的原位在线分析依赖于高性能的衰减全反射探头,衰减全反射技术是在线分析系统中实现原位在线测量的有力手段。通过分析衰减全反射技术的基本原理与特点,设计了一种成本低、光通量高、具有标准生物过程传感器接口的中红外衰减全反射探头,能够直接插入到生物反应器中,对生物过程反应物进行无损、零延迟的监测。实验结果表明,在线式atr探头具有较宽的光谱范围,所采集光谱具有较高的信噪比,能够应用在生物过程的在线定量分析之中。

关键词：生物过程在线监测 FTIR atr

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利用FTIR/atr快速测定大豆油的过氧化值

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中国粮油学报 2013年第4期28卷 108-112页

作者：杨本志潘秋月潘丹杰孟祥河浙江工业大学生物与环境工程学院杭州310018 中国农业大学食品科学与营养工程学院北京100000 杭州市粮油中心检验监测站杭州310014

利用傅里叶变换衰减全反射红外光谱法(FTIR/atr)简单快速地测定大豆油的过氧化值。采用偏最小二乘法(PLS)建立光谱数据与化学测定值之间的校准模型。油样根据过氧化物值分为高过氧化值(10～90 mmol/kg)和低过氧化值(0～10 mmol/kg),然... 详细信息

利用傅里叶变换衰减全反射红外光谱法(FTIR/atr)简单快速地测定大豆油的过氧化值。采用偏最小二乘法(PLS)建立光谱数据与化学测定值之间的校准模型。油样根据过氧化物值分为高过氧化值(10～90 mmol/kg)和低过氧化值(0～10 mmol/kg),然后根据分组波谱及全部波谱分别建模。选择合适的波长范围以及预处理方法,用验证样品集对定标方程进行验证,获得验证相关系数分别为0.999 9、0.996 0,定标集预测标准差(SEC)分别为0.27、0.21,验证集预测标准偏差(SEP)分别为0.58、0.25。FTIR/atr法的变异系数和相对偏差均优于化学法。因此模型具有较高的精密度和良好的稳定性,研究开发的FTIR/atr法分析油脂过氧化物值具有快速、准确环境友好等优点。

关键词： FTIR atr 过氧化值 PLS 检测大豆油

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