[1]阿依姆妮萨·阿卜杜热合曼,穆妮热·艾尼,米日阿依·吐尔迪,等.环状RNA hsa_circ0005273在急性髓系白血病中的表达及其调控肿瘤细胞生长和转移机制研究[J].陕西医学杂志,2026,(3):312-319.[doi:DOI:10.3969/j.issn.1000-7377.2026.03.004]
 AYIMUNISA Abudureheman,MUNIRE Aini,MIREAYI Tuerdi,et al.Expression of circular RNA hsa_circ0005273 in AML and its regulatory mechanism for tumor cell growth and metastasis[J].,2026,(3):312-319.[doi:DOI:10.3969/j.issn.1000-7377.2026.03.004]
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环状RNA hsa_circ0005273在急性髓系白血病中的表达及其调控肿瘤细胞生长和转移机制研究

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2026年3期
页码:
312-319
栏目:
基础研究
出版日期:
2026-03-05

文章信息/Info

Title:
Expression of circular RNA hsa_circ0005273 in AML and its regulatory mechanism for tumor cell growth and metastasis
作者:
阿依姆妮萨·阿卜杜热合曼穆妮热·艾尼米日阿依·吐尔迪努尔阿米娜·依明尼亚孜
(喀什地区第一人民医院血液内科,新疆 喀什 844000)
Author(s):
AYIMUNISA AbudurehemanMUNIRE AiniMIREAYI TuerdiNUERAMINA Yimingniyazi
(Department of Hematology,the first Pepople’s Hospital of Kashi Prefecture,Kashi 844000,China)
关键词:
急性髓系白血病环状RNA hsa_circ0005273微小RNA-143-3p增殖转移机制
Keywords:
Acute myeloid leukemiaCircular RNA hsa_circ0005273miR-143-3pProliferationMetastasisMechanism
分类号:
R -33
DOI:
DOI:10.3969/j.issn.1000-7377.2026.03.004
文献标志码:
A
摘要:
目的:探讨环状RNA hsa_circ0005273在急性髓系白血病(AML)中的表达及其对肿瘤细胞生长和转移的调控作用及其机制。方法:收集20例AML患者骨髓标本及2例健康骨髓捐献者标本,培养人正常骨髓基质细胞系和AML细胞系,采用实时荧光定量PCR(RT-qPCR)检测hsa_circ0005273及微小RNA(miR)-143-3p在临床样本与细胞系中的表达。将AML细胞系HL-60细胞分为对照组、si-NC组(转染si-NC)及si-hsa_circ0005273组(转染si-hsa_circ0005273),采用RT-qPCR检测转染效率,采用CCK-8法、集落形成实验、流式细胞术、Annexin V-FITC/PI双染法、Transwell小室实验分别观察细胞增殖活性、集落形成、周期分布、凋亡以及迁移与侵袭能力。利用StarBase数据库预测hsa_circ0005273与miR-143-3p结合位点,并通过双荧光素酶报告实验验证两者的靶向关系。结果:与健康志愿者骨髓相比,20例AML患者骨髓中hsa_circ0005273相对表达量上调(P<0.05)。AML细胞系中hsa_circ0005273相对表达量高于人正常骨髓基质细胞系(均P<0.05),HL-60细胞上调最为明显。与对照组和si-NC组比较,si-hsa_circ0005273组HL-60细胞中hsa_circ0005273相对表达量显著下调,说明转染成功。此外,与对照组和si-NC组比较,si-hsa_circ0005273组HL-60细胞增殖活性及集落形成数目降低,G2/M期比例增加,细胞凋亡率上升,迁移数目及侵袭数目减少(均P<0.05)。miR-143-3p在20例AML骨髓及各AML细胞系中的相对表达量要低于健康志愿者骨髓和人正常骨髓基质细胞系,而敲低hsa_circ0005273可使HL-60细胞内miR-143-3p相对表达量上调(均P<0.05)。经预测发现hsa_circ0005273与miR-143-3p存在互补结合位点。与转染阴性对照(NC)模拟物(mimic)与hsa_circ0005273野生型(WT)比较,共转染miR-143-3p mimic与hsa_circ0005273 WT的细胞中相对荧光素酶活性下降(均P<0.05)。结论:hsa_circ0005273在AML中高表达,敲低其表达可抑制AML细胞增殖,诱导G2/M期阻滞并促进凋亡,同时抑制细胞迁移与侵袭,其机制可能与其通过海绵吸附miR-143-3p有关。
Abstract:
Objective:To investigate the expression of the circular RNA hsa_circ0005273 in acute myeloid leukemia (AML) and its regulatory role and mechanism for tumor cell growth and metastasis.Methods:Bone marrow specimens were collected from 20 patients and from 2 healthy bone marrow donors.Normal human bone marrow stromal cell lines and AML cell lines were cultured.RT-qPCR was used to detect the expression of hsa_circ0005273 and miR-143-3p in clinical samples and cell lines.HL-60 cells were divided into control group,si-NC group (transfected with si-NC),and si-hsa_circ0005273 group (transfected with si-hsa_circ0005273),and RT-qPCR was used to detect transfection efficiency,and cell proliferation activity,colony formation,cell cycle distribution,apoptosis,and migration and invasion abilities were evaluated using CCK-8 assay,colony formation assay,flow cytometry,Annexin V-FITC/PI double staining,and Transwell chamber assay.The binding sites of hsa_circ0005273 and miR-143-3p were predicted using the StarBase database,and the targeting relationship between the two was verified using a dual-luciferase reporter assay.Results:Compared with the bone marrow of healthy volunteers,the relative expression level of hsa_circ0005273 was upregulated in the bone marrow of 20 AML patients (P<0.05).The relative expression level of hsa_circ0005273 in AML cell lines was higher than that in normal human bone marrow stromal cell lines (all P<0.05),and the upregulation was most significant in HL-60 cells.Compared with the control group and si-NC group,the relative expression level of hsa_circ0005273 in HL-60 cells in the si-hsa_circ0005273 group was significantly downregulated,indicating successful transfection.In addition,compared with the control group and si-NC group,the proliferation activity and colony formation number of HL-60 cells in the si-hsa_circ0005273 group decreased,the proportion of cells in the G2/M phase increased,the apoptosis rate increased,and the migration number and invasion number decreased (all P<0.05).The relative expression level of miR-143-3p in the bone marrow of 20 AML patients and various AML cell lines was lower than that in the bone marrow of healthy volunteers and the normal human bone marrow stromal cell lines,and knockdown of hsa_circ0005273 upregulated the relative expression level of miR-143-3p in HL-60 cells (all P<0.05).Prediction revealed that hsa_circ0005273 and miR-143-3p had complementary binding sites.The relative luciferase activity in cells co-transfected with miR-143-3p mimic and hsa_circ0005273 WT was decreased compared with that in cells transfected with NC mimic and hsa_circ0005273 WT (all P<0.05).Conclusion:Hsa_circ0005273 is highly expressed in AML.Knockdown of hsa_circ0005273 inhibits AML cell proliferation,induces G2/M arrest,and promotes apoptosis,while also inhibiting cell migration and invasion.This mechanism may be related to its sponging of miR-143-3p.

参考文献/References:

[1]ARBER D A,ORAZI A.The diagnostic spectrum of myelodysplastic syndromes and acute myeloid leukemia[J].Adv Anat Pathol,2025,32(4):299-306.
[2]COSTA A,SCALZULLI E,CARMOSINO I,et al.Clinical and biological advances of critical complications in acute myeloid leukemia[J].Leuk Lymphoma,2025,66(3):400-419.
[3]CHEN P,LIU X,ZHAO Y,et al.Global,national,and regional burden of acute myeloid leukemia among 60-89 years-old individuals:Insights from a study covering the period 1990 to 2019[J].Front Public Health,2024,11:1329529.
[4]ZHANG J,LUO Z,ZHENG Y,et al.CircRNA as an achilles heel of cancer:Characterization,biomarker and therapeutic modalities[J].J Transl Med,2024,22(1):752.
[5]KIM J.Circular RNAs:Novel players in cancer mechanisms and therapeutic strategies[J].Int J Mol Sci,2024,25(18):10121.
[6]易三凤,屈银宗,龚承先,等.环状RNA GRIN2B通过调控微小RNA-135b对食管癌细胞增殖和侵袭的影响实验研究[J].陕西医学杂志,2024,53(3):308-312.
[7]BONGOLO C C,ZHANG Y,DUAN S,et al.CircRNA ZFR promotes cell progression by regulating miR-96a-5p/SLC1A1 axis in hepatocellular carcinoma[J].Sci Rep,2025, 15(1):25546.
[8]SUN H,XIE Y,WU X,et al.CircRNAs as prognostic markers in pediatric acute myeloid leukemia[J].Cancer Lett,2024,591:216880.
[9]GUO H,CUI Y,BAI Y,et al.Screening of a prognostic gene signature for relapsed/refractory acute myeloid leukemia based on altered circulating circRNA profiles[J].Int J Gen Med,2024,17:2967-2979.
[10]YANG X,LIU J,LIU W,et al.CircFAM193B interaction with PRMT6 regulates AML leukemia stem cells chemoresistance through altering the oxidative metabolism and lipid peroxidation[J].Leukemia,2024,38(5):1057-1071.
[11]WANG X,JI C,HU J,et al.Hsa_circ_0005273 facilitates breast cancer tumorigenesis by regulating YAP1-hippo signaling pathway[J].J Exp Clin Cancer Res,2021,40(1):29.
[12]姜哲,韩佳慧,吴婷,等.环状RNA_0005273对食管癌细胞生物学行为的影响及可能机制[J].实用临床医药杂志,2023,27(9):46-52.
[13]YANG H,LI X,MENG Q,et al.CircPTK2 (hsa_circ_0005273) as a novel therapeutic target for metastatic colorectal cancer[J].Mol Cancer,2020,19(1):13.
[14]方前进,王润秋,李涛,等.宫颈脱落细胞中circ_0005273表达在宫颈癌诊断中的应用[J].安徽医学,2025,46(8):961-965.
[15]LABRADOR J,MARTNEZ-CUADRN D,BOLUDA B,et al.Evolving patterns and clinical outcome of genetic studies performed at diagnosis in acute myeloid leukemia patients:Real life data from the PETHEMA Registry[J].Cancer,2024,130(20):3436-3451.
[16]杨秋红,罗锦霞,王妙,等.复发/难治性急性髓系白血病VEN+LDAC方案挽救治疗期间SP70/MRD变化轨迹对预后的预测价值[J].陕西医学杂志,2025,54(9):1237-1242.
[17]SALLMAN D A,STAHL M.TP53-mutated acute myeloid leukemia:How can we improve outcomes?[J].Blood,2025,145(24):2828-2833.
[18]SHEN Y,JIA Y,ZHANG R,et al.Using circ-ANAPC7 as a novel type of biomarker in the monitoring of acute myeloid leukemia[J].Acta Haematol,2022,145(2):176-183.
[19]YAN L,YAN Q.Serum circRNA_100199 is a prognostic biomarker in acute myeloid leukemia[J].Int J Gen Med,2023,16:4661-4668.
[20]YANG X,WANG Y,RONG S,et al.Gene SH3BGRL3 regulates acute myeloid leukemia progression through circRNA_0010984 based on competitive endogenous RNA mechanism[J].Front Cell Dev Biol,2023,11:1173491.
[21]ZHANG W,ZHANG H,ZHAO X.Circ_0005273 promotes thyroid carcinoma progression by SOX2 expression[J].Endocr Relat Cancer,2020,27(1):11-21.
[22]PENG Y,CUI J,MA K,et al.Hsa_circ_0005273 acts as a sponge of miR-509-3p to promote the malignant behaviors of breast cancer by regulating HMMR expression[J].Thorac Cancer,2023,14(9):794-804.
[23]WU L,GAO J,LIU S,et al.CircRNA circ_0005273 contributes to the cisplatin resistance of cervical cancer cells by sponging miR-133b[J].J Obstet Gynaecol,2022,42(7):3086-3093.
[24]WANG G,CHENG T,YUAN H,et al.Tracing cellular interaction of circRNA-miRNA axis with Cu metal-organic framework supported DNA cascade assembly[J].Biosens Bioelectron,2023,228:115226.
[25]CHEN R X,LIU S C,KAN X C,et al.CircUGP2 suppresses intrahepatic cholangiocarcinoma progression via p53 signaling through interacting with PURB to regulate ADGRB1 transcription and sponging miR-3191-5p[J].Adv Sci (Weinh),2024,11(38):e2402329.
[26]KAMALI M J,SALEHI M,MOSTAFAVI M,et al.Hijacking and rewiring of host circRNA/miRNA/mRNA competitive endogenous RNA (ceRNA) regulatory networks by oncoviruses during development of viral cancers[J].Rev Med Virol,2024,34(2):e2530.
[27]ZHAO F,ZHANG X,PEI X,et al.Deregulated expression of circular RNAs is associated with immune evasion and leukemia relapse after allogeneic hematopoietic stem cell transplantation[J].Genes (Basel),2022,13(11):1986.
[28]LI H,BI K,FENG S,et al.CircRNA circ_POLA2 is upregulated in acute myeloid leukemia (AML) and promotes cell proliferation by suppressing the production of mature miR-34a[J].Cancer Manag Res,2021,13:3629-3637.
[29]WANG J,WU C,ZHOU W.CircPLXNB2 regulates acute myeloid leukemia progression through miR-654-3p/CCND1 axis[J].Hematology,2023,28(1):2220522.
[30]JU Y,CHOI G E,LEE M W,et al.Identification of miR-143-3p as a diagnostic biomarker in gastric cancer[J].BMC Med Genomics,2023,16(1):135.
[31]MANSOORI B,KIANI S,MEZAJIN A A,et al.MicroRNA-143-5p suppresses ER-positive breast cancer development by targeting oncogenic HMGA2[J].Clin Breast Cancer,2023,23(7):e480-e490.e3.
[32]张玲玲,张小霞,於潇潇,等.非小细胞肺癌患者血浆miR-520f、miR-143-3p表达与病理特征和预后的相关性研究[J].现代检验医学杂志,2022,37(3):69-72,78.
[33]华春波,陶宣辰,吕家誉,等.甲状腺癌组织miR-338、miR-143表达及其与患者临床病理特征和预后的关系[J].陕西医学杂志,2025,54(6):830-834.
[34]ARMSTRONG L,WILLOUGHBY C E,MCKENNA D J.Targeting of AKT1 by miR-143-3p suppresses epithelial-to-mesenchymal transition in prostate cancer[J].Cells,2023,12(18):2207.
[35]LIU Y,DU D,GU X,et al.MiR-143-3p/TET1 axis regulates GPC1 through DNA methylation and impairs the malignant biological behaviour of HCC via the hippo signalling pathway[J].J Cell Mol Med,2025,29(2):e70282.
[36]XU D,JIANG J,HE G,et al.MiR-143-3p represses leukemia cell proliferation by inhibiting KAT6A expression[J].Anticancer Drugs,2022,33(1):e662-e669.

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备注/Memo

备注/Memo:
新疆维吾尔自治区自然科学基金资助项目(2023D01F15)
更新日期/Last Update: 2026-03-05