急性髓系白血病患者外周血外泌体中miR-4286表达水平检测及其诊断价值

doi:10.13481/j.1671-587X.20230222

Abstract

Abstract:

Objective To detect the expression of miR-4286 in exosome in peripheral blood of the patients with acute myeloid leukemia（AML）， and to clarify the value of miR-4286 in the diagnosis of AML. Methods The peripheral blood samples from 45 newly diagnosed patients with AML （AML group） and 35 concurrent healthy subjects（control group） were collected.The exosomes from serum of the subjects in two groups were obtained by over speend contrifugation； the morphology of the centrifuged products was observed under transmission electron microscope（TEM）；and the particle diameter was detected by nanoparticle tracink analysis（NTA）； the expressions of surface markers CD63 and CD9 proteins were analyzed by Western blotting method；the expression levels of miR-4286 in exosome of the subjects in two groups were detected by real-time fluorescence quantitative PCR（RT-qPCR） method；the receiver operating characteristic （ROC） curve was used to calculate the area under curve （AUC）； the sensitivity and specificity of miR-4286 in the diagnosis of AML were analyzed. Results The TEM results showed that the extracted exosomes in peripheral blood showed a membrane structure with roundness in apperance and concave in the middle， and the diameter was about 30－100 nm；the NTA results showed that the particle sizes of exosomes were mainly distributed at 30－150 nm；the Western blotting results showed that the exosomes all expressed CD63 and CD9 proteins，with the typical characteristics of the exosomes.The RT-qPCR results showed that the expression level of exosome miR-4286 in peripheral blood of the patients in AML group was significantly higher than that in control group（Z=－5.543，P<0.01）. The ROC curve analysis showed that when the critical value of expression level of miR-4286 in exosome was 3.182， the AUC was 0.862 9（95%CI：0.774 7，0.937 1， P<0.01）， the sensitivity was 66.67%，the specificity was 97.14%，and the diagnostic efficacy was good. Conclusion The miR-4286 in exosome in peripheral blood has high diagnostic efficiency for AML；it can be used as a diagnostic marker for AML， and has high clinical diagnostic value.

Key words: Acute myeloid leukemia, Exosome, microRNA-4286, Diagnostic efficacy, Biomarker

CLC Number:

R446.11

Haiwei QUAN,Yali ZHANG,Han WANG,Yijiu AI,Yutong ZOU,Wei XIA. Detection of expression level of miR-4286 in exosome in peripheral blood of patients with acute myeloid leukemia and its diagnostic value[J].Journal of Jilin University(Medicine Edition), 2023, 49(2): 460-466.

Figures/Tables 5

References 34

1	BLOOMFIELD C D， ESTEY E， PLEYER L， et al. Time to repeal and replace response criteria for acute myeloid leukemia？［J］. Blood Rev， 2018，32（5）： 416-425.
2	KOWAL J， TKACH M， THÉRY C. Biogenesis and secretion of exosomes［J］. Curr Opin Cell Biol， 2014，29： 116-125.
3	HENDERSON M C， AZORSA D O. The genomic and proteomic content of cancer cell-derived exosomes［J］. Front Oncol， 2012，2： 38.
4	BENITES B D， SILVA SANTOS DUARTE A D A， LONGHINI A L F， et al. Exosomes in the serum of acute myeloid leukemia patients induce dendritic cell tolerance： Implications for immunotherapy［J］. Vaccine， 2019，37（11）： 1377-1383.
5	BOYIADZIS M， WHITESIDE T L. Exosomes in acute myeloid leukemia inhibit hematopoiesis［J］. Curr Opin Hematol， 2018，25（4）： 279-284.
6	XU Y C， LIN Y S， ZHANG L， et al. microRNAs of bone marrow mesenchymal stem cell-derived exosomes regulate acute myeloid leukemia cell proliferation and apoptosis［J］. Chin Med J （Engl）， 2020，133（23）： 2829-2839.
7	BARRERA-RAMIREZ J， LAVOIE J R， MAGANTI H B， et al. Micro-RNA profiling of exosomes from marrow-derived mesenchymal stromal cells in patients with acute myeloid leukemia： implications in leukemogenesis［J］. Stem Cell Rev Rep， 2017，13（6）： 817-825.
8	王卓然，朱冰，余丽梅，等. 干细胞衍生的外泌体在肝脏疾病治疗中的作用［J］.临床肝胆病杂志，2023，39（3）：699-706.
9	ZHANG L， KHADKA B， WU J Y， et al. Bone marrow mesenchymal stem cells-derived exosomal miR-425-5p inhibits acute myeloid leukemia cell proliferation， apoptosis， invasion and migration by targeting WTAP［J］. Onco Targets Ther， 2021，14： 4901-4914.
10	JIANG D F， WU X， SUN X Y， et al. Bone mesenchymal stem cell-derived exosomal microRNA-7-5p inhibits progression of acute myeloid leukemia by targeting OSBPL11［J］.J Nanobiotechnol，2022，20（1）：29.
11	CHENG H， DING J， TANG G S， et al. Human mesenchymal stem cells derived exosomes inhibit the growth of acute myeloid leukemia cells via regulating miR-23b-5p/TRIM14 pathway［J］. Mol Med， 2021，27（1）： 128.
12	ZHAO C， ZHAO Y， ZHAO J Q， et al. Acute myeloid leukemia cell-derived extracellular vesicles carrying microRNA-548ac regulate hematopoietic function via the TRIM28/STAT3 pathway［J］. Cancer Gene Ther， 2022， 29（7）： 918-929.
13	JIANG L J， DENG T R， WANG D， et al. Elevated serum exosomal miR-125b level as a potential marker for poor prognosis in intermediate-risk acute myeloid leukemia［J］. Acta Haematol， 2018，140（3）： 183-192.
14	LIN X， LING Q， LV Y F， et al. Plasma exosome-derived microRNA-532 as a novel predictor for acute myeloid leukemia［J］. Cancer Biomark， 2020，28（2）： 151-158.
15	FANG Z G， WANG X Z， WU J Y， et al. High serum extracellular vesicle miR-10b expression predicts poor prognosis in patients with acute myeloid leukemia［J］. Cancer Biomark， 2020，27（1）： 1-9.
16	HORNICK N I， HUAN J Y， DORON B， et al. Serum exosome microRNA as a minimally-invasive early biomarker of AML［J］. Sci Rep， 2015，5： 11295.
17	HORIGUCHI H， KOBUNE M， KIKUCHI S， et al. Extracellular vesicle miR-7977 is involved in hematopoietic dysfunction of mesenchymal stromal cells via poly（rC） binding protein 1 reduction in myeloid neoplasms［J］. Haematologica， 2016，101（4）： 437-447.
18	ARBER D A， ORAZI A， HASSERJIAN R， et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia［J］. Blood， 2016，127（20）： 2391-2405.
19	MARQUÉS-GARCÍA F， ISIDORO-GARCÍA M. Protocols for exosome isolation and RNA profiling［J］. Methods Mol Biol， 2016，1434： 153-167.
20	DÖHNER H， WEISDORF D J， BLOOMFIELD C D. Acute myeloid leukemia［J］. N Engl J Med， 2015，373（12）： 1136-1152.
21	HANDSCHUH L. Not only mutations matter： molecular picture of acute myeloid leukemia emerging from transcriptome studies［J］. J Oncol， 2019，2019： 7239206.
22	DÖHNER H， ESTEY E， GRIMWADE D， et al. Diagnosis and management of AML in adults： 2017 ELN recommendations from an international expert panel［J］. Blood， 2017，129（4）： 424-447.
23	SASAKI R， KANDA T， YOKOSUKA O， et al. Exosomes and hepatocellular carcinoma： from bench to bedside［J］. Int J Mol Sci， 2019，20（6）：1406.
24	KOK V C， YU C C. Cancer-derived exosomes： their role in cancer biology and biomarker development［J］. Int J Nanomed， 2020，15： 8019-8036.
25	ZHAI L Y， LI M X， PAN W L， et al. In situ detection of plasma exosomal microRNA-1246 for breast cancer diagnostics by a Au nanoflare probe［J］. ACS Appl Mater Interfaces， 2018，10（46）： 39478-39486.
26	STEVIC I， MÜLLER V， WEBER K， et al. Specific microRNA signatures in exosomes of triple-negative and HER2-positive breast cancer patients undergoing neoadjuvant therapy within the GeparSixto trial［J］. BMC Med， 2018，16（1）： 179.
27	HONG C S， DANET-DESNOYERS G， SHAN X C， et al. Human acute myeloid leukemia blast-derived exosomes in patient-derived xenograft mice mediate immune suppression［J］. Exp Hematol， 2019，76： 60-66.
28	CHEN T T， ZHANG G Z， KONG L Z， et al. Leukemia-derived exosomes induced IL-8 production in bone marrow stromal cells to protect the leukemia cells against chemotherapy［J］. Life Sci， 2019，221： 187-195.
29	WANG B， WANG X T， HOU D Y， et al. Exosomes derived from acute myeloid leukemia cells promote chemoresistance by enhancing glycolysis-mediated vascular remodeling［J］. J Cell Physiol， 2019，234（7）： 10602-10614.
30	ZHANG M， TIAN H， LI R R， et al. microRNA-4286 promotes esophageal carcinoma development by targeting INPP4A to evoke the JAK2/STAT3 pathway activation［J］. Pharmazie， 2018，73（6）： 342-348.
31	LING C H， WANG X T， ZHU J J， et al. microRNA-4286 promotes cell proliferation， migration， and invasion via PTEN regulation of the PI3K/Akt pathway in non-small cell lung cancer［J］. Cancer Med， 2019，8（7）： 3520-3531.
32	HE Z， XUE H， LIU P， et al. miR-4286/TGF-β1/Smad3-negative feedback loop ameliorated vascular endothelial cell damage by attenuating apoptosis and inflammatory response［J］. J Cardiovasc Pharmacol， 2020，75（5）： 446-454.
33	TSAI C C， CHEN T Y， TSAI K J， et al. NF-κB/miR-18a-3p and miR-4286/BZRAP1 axis may mediate carcinogenesis in Helicobacter pylori-associated gastric cancer［J］. Biomed Pharmacother， 2020，132： 110869.
34	HO K H， CHEN P H， SHIH C M， et al. miR-4286 is involved in connections between IGF-1 and TGF-β signaling for the mesenchymal transition and invasion by glioblastomas［J］. Cell Mol Neurobiol， 2022， 42（3）： 791-806.

[1]	Han WANG,Yali ZHANG,Haiwei QUAN,Runhong MU,Yutong ZOU,Wei XIA. Expression of miR-92a-3p in exosome in serum of patients with acute myeloid leukemia and its significance [J]. Journal of Jilin University(Medicine Edition), 2023, 49(2): 467-472.
[2]	Wentao WANG,Xuguang MI,Yang ZHOU,Wenxing PU,Jiaxu GAO,Meng JING,Fankai MENG. Effect of autophagy induced by exosomes derived from bone marrow mesenchymal stem cells on survival of SH-SY5Y cells inhibited by MPP⁺ and its mechanism [J]. Journal of Jilin University(Medicine Edition), 2022, 48(3): 606-614.
[3]	Weihang LI,Ziyi DING,Dong WANG,Yikai PAN,Yuhui LIU,Shilei ZHANG,Jing LI,Ming YAN. Bioinformatics analysis based on screening of core driving genes in osteosarcoma and construction of gene model for prediction of survival time of patients [J]. Journal of Jilin University(Medicine Edition), 2021, 47(6): 1570-1580.
[4]	Jing YANG, Mingzhi XU, Dongwei ZHANG, Yanan DONG, Yi WANG, Haifeng SONG. Establishment of process method for large-scale preparation of bovine milk exosomes with high purity and identification of its molecular and cellular biological activities [J]. Journal of Jilin University(Medicine Edition), 2021, 47(3): 777-787.
[5]	Yuqing PAN, Yunyan SUN, Yixun LI, Liying WANG, Zhuoma SINAN, Rui CHEN, Xi ZHANG, Yan DU. Construction and analysis of competitive endogenous RNA networks in acute myeloid leukemia based on high-throughput microarray [J]. Journal of Jilin University(Medicine Edition), 2021, 47(3): 669-676.
[6]	Xiaohui LI, Ziwei QU, Xin LU, Qingbin MENG, Huatao CHEN, Jun REN, Chengpei TAN. Regulatory effect of exosomes carrying miR-196b-5p derived from bone marrow mesenchymal stem cells on biological characteristics of colon cancer cells [J]. Journal of Jilin University(Medicine Edition), 2021, 47(3): 660-668.
[7]	ZHANG Xi, ZHAI Li, SUN Yunyan, YANG Wei, GAO Yanzhang, LEI Ming, PAN Yuqing. Bioinformatics analysis of pediatric acute myeloid leukemia based on high-throughput microarray [J]. Journal of Jilin University(Medicine Edition), 2020, 46(05): 1036-1042.
[8]	LIU Jing, WANG Jing, GE Jing, FENG Yanping, FANG Guiying, WANG Xu, YANG Yanhong, LI Lin. Effect of HeLa cell exosomes on migration and invasion and its mechanism of Wnt/ β-catenin signaling pathway [J]. Journal of Jilin University(Medicine Edition), 2020, 46(04): 798-803.
[9]	WANG Jing, GE Jing, WANG Xu, FANG Guiying, DAI Lili, LIU Jing. Effect of berberine hydrochloride on exosomes of cervical cancer HeLa cells and its mechanism [J]. Journal of Jilin University(Medicine Edition), 2020, 46(04): 779-785.
[10]	SU Long, ZHANG Yunwei, WANG Zhuo, SONG Fei, QIN Tianxue, GAO Sujun. Proliferation inhibition and pro-apoptotic effects of shikonin on human leukemia MV4-11 cells [J]. Journal of Jilin University(Medicine Edition), 2020, 46(01): 96-101.
[11]	LI Gang, WANG Jiansheng, QIN Sida, SUN Xin, REN Hong, ZHANG Jing, LI Baocheng. Application of detection of circulating tumor cells and exosome miR-21 in diagnosis of lung ground glass opacity [J]. Journal of Jilin University(Medicine Edition), 2019, 45(03): 587-594.
[12]	TIAN Dachuan, LI Haile, XIAO Dawei, ZHOU Shanjian, SU Yongwei, LIU Danping, QI Hui. Promotion effect of cartilage regenerated scaffolds combined with exosomes derived from mutant type of HIF-1α modified BMSCs in repairing advanced cartilage defects [J]. Journal of Jilin University Medicine Edition, 2018, 44(02): 216-222.
[13]	XU Bing, LI Haile, LIU Danping, ZHANG Fengwei. Promotion of exosomes derived frombone-marrow endothelial progenitor cellsin repairing traumatic cutaneous deficiency in rats [J]. Journal of Jilin University Medicine Edition, 2017, 43(04): 672-678.
[14]	LI Qian, LI Jingao, ZHOU Maohua, LIAO Pengjun, PENG Qi, CHEN Jing, CHEN Shaoxian, WEI Shanshan, HUANG Huiting, SHE Miaorong. Relationship between CD56 antigen expression in leukemia cells and prognosis of patients with acute myeloid leukemia [J]. Journal of Jilin University Medicine Edition, 2016, 42(02): 283-289.
[15]	WEI Shanshan, ZHOU Maohua, LI Jingao, CHEN Jing, CHEN Shaoxian, LI Qian, XIA Pingfang, PENG Qi, SHE Miaorong. Expressions of CD34 and CD38 antigens in leukemia cells of patients with acute myeloid leukemia and their clinical significances [J]. Journal of Jilin University Medicine Edition, 2015, 41(02): 362-368.

Detection of expression level of miR-4286 in exosome in peripheral blood of patients with acute myeloid leukemia and its diagnostic value

RichHTML

PDF (PC)

Like

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 5

References 34

Related Articles 15

Metrics

Comments

Recommended 0