PKMYT1在乳腺癌中表达...息学分析及实验用细胞系筛选_安彦榕.pdf

参考文献1 程方,李晓.糖皮质激素致股骨头坏死的病理生理机制研究进展J.全科口腔医学电子杂志,2020,7(6):10-212 李时斌,赖渝,周毅,等.激素性股骨头坏死发病机制及相关信号通路的靶点效应J.中国组织工程研究,2021,25(6):935-9413 Dong CH,Deng YS,Yang XJ,et al.The interplay of transcriptionaland post-transcriptional regulation of migration of mesenchymal stemcells during early stages of bone fracture healingJ.Eur Rev MedPharmacol Sci,2017,21(1):5542-55474 Bian EB,Xiong ZG,Li J.New advances of lncRNAs in liver fibrosis,with specific focus on lncRNA-miRNA interactionsJ.J Cell Phys-iol,2019,234(5):2194-22035 Zhang W,Dong R,Diao S,et al.Differential long noncoding RNA/mRNA expression profiling and functional network analysis during os-teogenic differentiation of human bone marrow mesenchymal stem cellsJ.Stem Cell Res Ther,2017,8(1):1-136 Li S,Hu C,Li J,et al.Effect of miR-26a-5p on the Wnt/Ca2+pathway and osteogenic differentiation of mouse adipose-derived mes-enchymal stem cellsJ.Calcif Tissue Int,2016,99(1):174-1867 Liu B,Yang F,Wei X,et al.An exploratory study of articular carti-lage and subchondral bone reconstruction with bone marrow mesenchy-mal stem cells combined with porous tantalum/Bio-Gide collagenmembrane in osteonecrosis of the femoral headJ.Mater Sci Eng CMater Biol Appl,2019,99(4):1123-11328 Xu Y,Jiang Y,Wang Y,et al.LINC00473 regulated apoptosis,pro-liferation and migration but could not reverse cell cycle arrest of humanbone marrow mesenchymal stem cells induced by a high-dosage ofdexamethasoneJ.Stem Cell Res,2020,48(8):11-239 Wan Y,Yao Z,Chen W,et al.The lncRNA NORAD/miR-520a-3p facilitates malignancy in non-small cell lung cancer via PI3k/Akt/mTOR signaling pathway J.Onco Targets Ther,2020,13(5):1533-154410Huang XZ,Huang J,Li WZ,et al.LncRNA-MALAT1 promotesosteogenic differentiation through regulating ATF4 by sponging miR-214:implication of steroid-induced avascular necrosis of the femoralheadJ.Steroids,2020,154(3):31-4511Wei B,Wei W,Zhao B,et al.Long non-coding RNA HOTAIR in-hibits miR-17-5p to regulate osteogenic differentiation and prolifer-ation in non-traumatic osteonecrosis of femoral headJ.PLoS One,2017,12(6):e016909712Jia J,Feng X,Xu W,et al.MiR-17-5p modulates osteoblasticdifferentiation and cell proliferation by targeting Smad7 in non-trau-matic osteonecrosisJ.Exp Mol Med,2014,25(1):43-5613纪元元,李劲峰,寇红伟,等.微小 RNA-23a-3p 负调控Runx2 基因抑制骨髓间充质干细胞成骨分化诱导绝经后骨质疏松的研究J.中华实验外科杂志,2022,39(1):112-11514Yuan S,Zhang C,Zhu Y,et al.Neohesperidin ameliorates steroid-induced osteonecrosis of the femoral head by inhibiting the histonemodification of lncRNA HOTAIRJ.Drug Des Devel Ther,2020,14(3):5419-543015Kalwa M,Hnzelmann S,Otto S,et al.The lncRNA HOTAIR im-pacts on mesenchymal stem cells via triple helix formationJ.Nucle-ic Acids Res,2016,44(22):10631-10643(收稿日期:2022-01-29)(修回日期:2022-04-08)基金项目:内蒙古自治区科技计划项目(2019GG083)作者单位:010030呼和浩特,内蒙古医科大学基础医学院(安彦榕),病理学教研室(贾永峰)通信作者:贾永峰,电子信箱:yfjia0471 PKMYT1 在乳腺癌中表达的生物信息学分析及实验用细胞系筛选安彦榕贾永峰摘要目的基于生物信息学研究 PKMYT1 基因在乳腺癌进展中的作用及影响以及在乳腺癌各细胞系中的表达情况。方法将癌症基因组图谱(the cancer genome atlas,TCGA)乳腺癌 RNA 转录组数据中的 PKMYT1 进行单基因分析,其中包括差异分析、配对差异分析、临床相关性分析、GSEA 富集分析及生存分析,同时还利用 GEPIA 2、TIMER2.0、The Human Protein Atlas 及Kaplan-Meier Plotter 数据库进行了多次验证。且通过实时荧光定量 PCR 检测了 PKMYT1 在乳腺癌各细胞系中的表达情况,为后续研究筛选合适的细胞系。结果经生物信息学分析发现在乳腺癌中与正常样本比较,PKMYT1 在肿瘤样本中的表达明显升高(P 0.05);临床相关性分析结果表明,PKMYT1 在乳腺癌中与年龄、肿瘤分期及原发肿瘤直径相关(P 0.05);GSEA 富集分析显示在乳腺癌中 PKMYT1 高表达时,其功能富集与细胞周期、DNA复制、同源重组等功能密切相关,低表达时则与 TGF-信号通路、MAPK 信号通路等相关;生存分析发现 PKMYT1 在乳腺癌中HR=1.22 提示为高风险因素,且与生存相关(P 0.05)。同时细胞实验验证了 PKMYT1 在人乳腺癌细胞系中以正常乳腺细胞46论著J Med Res,February 2023,Vol.52 No.2系为参照在 MDA-MB-231 中表达最高,在小鼠乳腺癌细胞系中 4T1 细胞系表达最高。结论PKMYT1 是一种与乳腺癌恶性肿瘤相关的基因,是一种新的肿瘤标志物,或可成为乳腺癌新的治疗靶点。关键词乳腺癌PKMYT1 基因增殖肿瘤标志物中图分类号R737.9文献标识码ADOI 10.11969/j.issn.1673-548X.2023.02.013Bioinformatics Analysis of PKMYT1 Expression in Breast Cancer and Screening of Experimental Cell Lines.AN Yanrong,JIA Yongfeng.Basic Medical College,Inner Mongolia Medical University,Inner Mongolia 010030,ChinaAbstractObjectiveTo explore the role and impact of PKMYT1 gene in breast cancer progression and its expression in variousbreast cancer cell lines based on bioinformatics.MethodsSingle-gene analysis of PKMYT1,including differential analysis,paired dif-ferential analysis,clinical correlation analysis,Gene Set Enrichment Analysis(GSEA)and survival analysis were performed by breastcancer RNA transcriptome data from The Cancer Genome Atlas(TCGA),along with GEPIA 2,TIMER 2.0,The Human Protein Atlasand Kaplan-Meier Plotter databases were used for multiple validation.And the expression of PKMYT1 in various cell lines of breastcancer was detected by real-time fluorescence quantitative polymerase chain reaction to screen suitable cell lines for subsequent studies.ResultsBioinformatics analysis showed that the expression of PKMYT1 in breast cancer was significantly increased compared with that innormal samples(P 0.05);clinical correlation analysis showed that PKMYT1 was correlated with age,tumor stage and primary tumorsize in breast cancer(P 0.05).GSEA showed thatwhen PKMYT1 was highly expressed in breast cancer,its fu