Long non-coding RNAs(lncRNAs)have been implicated in cancer progression and drug resistance development.Moreover,there is evidence that lncRNA HOX transcript antisense intergenic RNA(HOTAIR)is involved in colorectal c...Long non-coding RNAs(lncRNAs)have been implicated in cancer progression and drug resistance development.Moreover,there is evidence that lncRNA HOX transcript antisense intergenic RNA(HOTAIR)is involved in colorectal cancer(CRC)progression.The present study aimed to examine the functional role of lncRNA HOTAIR in conferring radiotherapy resistance in CRC cells,as well as the underlying mechanism.The relative expression levels of HOTAIR were examined in 70 pairs of CRC tumor and para-cancerous tissues,as well as in radiosensitive and radioresistant samples.The correlations between HOTAIR expression levels and clinical features of patients with CRC were assessed using the Chi-square test.Functional 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 radiation.RNA 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 samples.The elevated expression of HOTAIR was correlated with more advanced histological grades,distance metastasis and the poor prognosis in patients with CRC.Silencing HOTAIR suppressed the proliferation and promoted apoptosis and radiosensitivity in CRC cells.HOTAIR knockdown also inhibited the tumorigenesis of CRC cells and enhanced the sensitivity to radiotherapy in a mouse xenograft model.Moreover,the data showed that HOTAIR could interact with ATR to regulate the DNA damage repair signaling pathway.Silencing HOTAIR impaired the ATR-ATR interacting protein(ATRIP)complex and signaling in cell cycle progression.Collectively,the present results indicate that lncRNA HOTAIR facilitates the DNA damage response pathway and promotes radioresistance in CRC cells by targeting ATR.展开更多
目的探讨非创伤性股骨头坏死(ONFH)患者血清和股骨头局部LncRNA HOX转录反义RNA(HOTAIR)的表达与疾病严重程度的关系。方法纳入本院接收的保髋或全髋置换的非创伤性ONFH患者90例,健康对照84例。RT-PCR检测血清和局部HOTAIR的表达,影像...目的探讨非创伤性股骨头坏死(ONFH)患者血清和股骨头局部LncRNA HOX转录反义RNA(HOTAIR)的表达与疾病严重程度的关系。方法纳入本院接收的保髋或全髋置换的非创伤性ONFH患者90例,健康对照84例。RT-PCR检测血清和局部HOTAIR的表达,影像学进展由国际骨循环研究学会(ARCO)分期判定,采用VAS和Harris髋关节评分评价ONFH患者临床严重程度,应用ROC曲线确定血清HOTAIR在影像学进展中的诊断价值。结果非创伤性ONFH患者血清HOTAIR表达高于健康对照组(1.97±0.32 vs 1.00±0.10,P<0.001),ONFH组织中的局部HOTAIR在坏死区高于非坏死区(2.37±0.25 vs 1.00±0.10,P<0.001)。ARCO 4级的ONFH患者血清和局部HOTAIR表达高于3级(2.22±0.28 vs 1.94±0.36,P=0.001;2.58±0.22 vs 2.42±0.32,P=0.02)。ARCO 3级的ONFH患者与ARCO 1/2级相比,血清HOTAIR表达升高(1.94±0.36 vs 1.73±0.23,P=0.009;2.42±0.32 vs 2.13±0.24,P<0.001)。血清中和局部HOTAIR的表达与ARCO分级呈显著正相关(r=0.569,P<0.001;r=0.585,P<0.001)。血清和局部HOTAIR表达与VAS评分呈正相关(血清r=0.557,P<0.001;局部r=0.672,P<0.001),与HSS评分呈显著负相关(血清r=-0.326,P=0.002;局部r=-0.489,P<0.001)。ROC曲线分析显示,血清HOTAIR可作为诊断非创伤性ONFH影像学进展的良好指标(AUC=0.663,P=0.030;AUC=0.726,P=0.003)。结论非创伤性ONFH患者血清和局部HOTAIR表达升高可能反映ONFH病情的严重程度。展开更多
基金This study was supported by the Inner Mongolia Science and Technology Department Science and Technology Research Project(No.2021GG0270)National Natural Science Foundation of China(81860534)+5 种基金Natural Science Foundation of Inner Mongolia(2021MS08152)Program for Young Talents of Science and Technology in Universities of Inner Mongolia Autonomous Region(NJYT22004)Scientific and Technological Innovative Research Team for Inner Mongolia Medical University of Transformation Application of Organoid in Medical and Industrial Interdiscipline(YKD2022TD002)Major Project of Inner Mongolia Medical University(YKD2022 ZD002)Radiobiology System and Team Construction of Radiotherapy for Inner Mongolia Medical University(YKD2022XK014)Key Laboratoy of Radiation Physics and Biology of Inner Mongolia Medical University(PIKY2023030).
文摘Long non-coding RNAs(lncRNAs)have been implicated in cancer progression and drug resistance development.Moreover,there is evidence that lncRNA HOX transcript antisense intergenic RNA(HOTAIR)is involved in colorectal cancer(CRC)progression.The present study aimed to examine the functional role of lncRNA HOTAIR in conferring radiotherapy resistance in CRC cells,as well as the underlying mechanism.The relative expression levels of HOTAIR were examined in 70 pairs of CRC tumor and para-cancerous tissues,as well as in radiosensitive and radioresistant samples.The correlations between HOTAIR expression levels and clinical features of patients with CRC were assessed using the Chi-square test.Functional 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 radiation.RNA 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 samples.The elevated expression of HOTAIR was correlated with more advanced histological grades,distance metastasis and the poor prognosis in patients with CRC.Silencing HOTAIR suppressed the proliferation and promoted apoptosis and radiosensitivity in CRC cells.HOTAIR knockdown also inhibited the tumorigenesis of CRC cells and enhanced the sensitivity to radiotherapy in a mouse xenograft model.Moreover,the data showed that HOTAIR could interact with ATR to regulate the DNA damage repair signaling pathway.Silencing HOTAIR impaired the ATR-ATR interacting protein(ATRIP)complex and signaling in cell cycle progression.Collectively,the present results indicate that lncRNA HOTAIR facilitates the DNA damage response pathway and promotes radioresistance in CRC cells by targeting ATR.
文摘目的探讨非创伤性股骨头坏死(ONFH)患者血清和股骨头局部LncRNA HOX转录反义RNA(HOTAIR)的表达与疾病严重程度的关系。方法纳入本院接收的保髋或全髋置换的非创伤性ONFH患者90例,健康对照84例。RT-PCR检测血清和局部HOTAIR的表达,影像学进展由国际骨循环研究学会(ARCO)分期判定,采用VAS和Harris髋关节评分评价ONFH患者临床严重程度,应用ROC曲线确定血清HOTAIR在影像学进展中的诊断价值。结果非创伤性ONFH患者血清HOTAIR表达高于健康对照组(1.97±0.32 vs 1.00±0.10,P<0.001),ONFH组织中的局部HOTAIR在坏死区高于非坏死区(2.37±0.25 vs 1.00±0.10,P<0.001)。ARCO 4级的ONFH患者血清和局部HOTAIR表达高于3级(2.22±0.28 vs 1.94±0.36,P=0.001;2.58±0.22 vs 2.42±0.32,P=0.02)。ARCO 3级的ONFH患者与ARCO 1/2级相比,血清HOTAIR表达升高(1.94±0.36 vs 1.73±0.23,P=0.009;2.42±0.32 vs 2.13±0.24,P<0.001)。血清中和局部HOTAIR的表达与ARCO分级呈显著正相关(r=0.569,P<0.001;r=0.585,P<0.001)。血清和局部HOTAIR表达与VAS评分呈正相关(血清r=0.557,P<0.001;局部r=0.672,P<0.001),与HSS评分呈显著负相关(血清r=-0.326,P=0.002;局部r=-0.489,P<0.001)。ROC曲线分析显示,血清HOTAIR可作为诊断非创伤性ONFH影像学进展的良好指标(AUC=0.663,P=0.030;AUC=0.726,P=0.003)。结论非创伤性ONFH患者血清和局部HOTAIR表达升高可能反映ONFH病情的严重程度。
