Effect of circDCUN1D4 on proliferation,apoptosis and immune escape of lung cancer cells by regulating the miR-18a-5p/FBP1 axis

SHI Chun-hui; LIN Jian-ping; WU Chao

doi:10.11659/jjssx.12E022012

您当前的位置：

首页 >

文章列表页 >

Effect of circDCUN1D4 on proliferation,apoptosis and immune escape of lung cancer cells by regulating the miR-18a-5p/FBP1 axis

Basic Research | 更新时间：2024-01-22

- Effect of circDCUN1D4 on proliferation,apoptosis and immune escape of lung cancer cells by regulating the miR-18a-5p/FBP1 axis
- JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY Vol. 33, Issue 1, Pages: 19-23(2024)
- 作者机构：
  
  1.宝鸡市中医医院肿瘤科，陕西宝鸡 721000
  2.宝鸡市中医医院呼吸与危重症医学科，陕西宝鸡 721000
  3.西安国际医学中心医院呼吸内科，陕西西安 710000
- 作者简介：
- 基金信息：
- DOI：10.11659/jjssx.12E022012
  CLC： R734.2
- Published：25 January 2024，
  
  Received：02 December 2022，
扫描看全文
史春辉,蔺建平,吴超.circDCUN1D4调节miR-18a-5p/FBP1轴对肺癌细胞增殖、凋亡和免疫逃逸的影响[J].局解手术学杂志,2024,33(01):19-23.

SHI Chun-hui,LIN Jian-ping,WU Chao.Effect of circDCUN1D4 on proliferation,apoptosis and immune escape of lung cancer cells by regulating the miR-18a-5p/FBP1 axis[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2024,33(01):19-23.
史春辉,蔺建平,吴超.circDCUN1D4调节miR-18a-5p/FBP1轴对肺癌细胞增殖、凋亡和免疫逃逸的影响[J].局解手术学杂志,2024,33(01):19-23. DOI： 10.11659/jjssx.12E022012.

SHI Chun-hui,LIN Jian-ping,WU Chao.Effect of circDCUN1D4 on proliferation,apoptosis and immune escape of lung cancer cells by regulating the miR-18a-5p/FBP1 axis[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2024,33(01):19-23. DOI： 10.11659/jjssx.12E022012.

摘要

目的

探讨环状RNA（circRNA）DCUN1D4调节微小RNA（miR）-18a-5p/果糖-1

6-二磷酸酶1（FBP1）轴对肺癌细胞增殖、凋亡和免疫逃逸的影响。

方法

选取人肺癌细胞系（H1975、H1650、A549、SPCA-1）和人正常肺表皮细胞（HPL-1），qRT-PCR检测各种细胞中circDCUN1D4、miR-18a-5p、FBP1 mRNA表达水平。取对数生长期的A549细胞并分为空白组、circDCUN1D4过表达质粒（circDCUN1D4）组、过表达质粒阴性对照（NC）组、circDCUN1D4+miR-18a-5p模拟物阴性对照（circDCUN1D4+mimics NC）组、circDCUN1D4+miR-18a-5p模拟物（circDCUN1D4+miR-18a-5p mimics）组。CCK-8法检测各组A549细胞活力，流式细胞术检测各组A549细胞凋亡水平，qRT-PCR检测各组A549细胞中circDCUN1D4、miR-18a-5p、FBP1 mRNA表达水平，Western blot检测各组A549细胞中FBP1、caspase-3、Ki67、增殖细胞核抗原（PCNA）及程序性死亡分子配体-1（PD-L1）表达水平，双荧光素酶实验验证miR-18a-5p分别与circDCUN1D4、FBP1的靶向关系。

结果

与HPL-1细胞相比，人肺癌细胞系中circDCUN1D4、FBP1 mRNA表达显著下降（

0.05），miR-18a-5p表达显著增加（

0.05）。miR-18a-5p分别与circDCUN1D4、FBP1存在靶向关系。与空白组、NC组相比，circDCUN1D4组细胞24 h和48 h的OD值、Ki67、PCNA、miR-18a-5p、PD-L1表达显著降低（

0.05），细胞凋亡率、circDCUN1D4、FBP1、caspase-3表达显著增加（

0.05）；过表达miR-18a-5p逆转了circDCUN1D4对肺癌细胞恶性行为的抑制作用（

0.05）。

结论

circDCUN1D4过表达可以促进肺癌细胞凋亡，抑制肺癌细胞增殖及免疫逃逸，其作用机制可能与调控miR-18a-5p/FBP1轴有关。

Abstract

Objective

To investigate the influences of circular RNA （circRNA） DCUN1D4 on the proliferation，apoptosis and immune escape of lung cancer cells by regulating the microRNA （miR）-18a-5p/fructose-1，6-bisphosphatase 1 （FBP1） axis.

Methods

The human lung cancer cell lines H1975，H1650，A549 and SPCA-1 and human normal lung epidermal cells HPL-1 were selected，qRT-PCR was used to detect the expression levels of circDCUN1D4，miR-18a-5p and FBP1 mRNA in various cells.A549 cells in logarithmic growth phase were selected and divided into the blank group，circDCUN1D4 overexpression plasmid （circDCUN1D4） group，overexpression plasmid negative control （NC） group，circDCUN1D4+miR-18a-5p mimics negative control （circDCUN1D4+mimics NC） group，and circDCUN1D4+miR-18a-5p mimics group. The cell viability of each group was detected by CCK-8 method，the cell apoptosis was detected by flow cytometry，the expression levels of circDCUN1D4，miR-18a-5p and FBP1 mRNA of cells in each group were detected by qRT-PCR，the expression levels of FBP1，caspase-3，Ki67，proliferating cell nuclear antigen （PCNA） and programmed death ligand-1 （PD-L1）were detected by Western blot，the targeting relationships of miR-18a-5p with circDCUN1D4 and FBP1 were verified by dual luciferase assay.

Results

Compared with HPL-1 cells，the mRNA expressions of circDCUN1D4 and FBP1 were significantly decreased （

0.05），and the expression of miR-18a-5p was significantly increased （

0.05）.miR-18a-5p had targeting relationships with circDCUN1D4 and FBP1，respectively. Compared with the blank group and NC group，the OD values at 24 hours and 48 hours，and the expressions of Ki67，PCNA，miR-18a-5p and PD-L1 of cells in the circDCUN1D4 group were significantly decreased（

0.05），and the apoptosis rate，and the expressions of circDCUN1D4，FBP1 and caspase-3 were significantly increased （

0.05）.Overexpression of miR-18a-5p reversed the inhibitory effect of circDCUN1D4 on the malignant behavior of lung cancer cells （

0.05）.

Conclusion

Overexpression of circDCUN1D4 can promote lung cancer cell apoptosis，inhibit lung cancer cell proliferation and immune escape，and its mechanism may be related to the regulation of miR-18a-5p/FBP1 axis.

关键词

circDCUN1D4miR-18a-5p/FBP1轴肺癌增殖凋亡免疫逃逸

Keywords

circDCUN1D4miR-18a-5p/FBP1 axislung cancerproliferationapoptosisimmune escape

references

邵为朋，王晓伟，刘德若.小细胞肺癌目前治疗的策略与未来方向［J］.中国肺癌杂志，2017，20（6）：421-426.doi：10.3779/j.issn.1009-3419.2017.06.09http://dx.doi.org/10.3779/j.issn.1009-3419.2017.06.09.

陈天佑，熊飞，张倬，等.LncRNA IGF2-AS基因通过靶向miR-370-3p对肺癌细胞增殖和凋亡的影响［J］.中国老年学杂志，2021，41（23）：5308-5313.doi：10.3969/j.issn.1005-9202http://dx.doi.org/10.3969/j.issn.1005-9202.

国家癌症中心，国家肿瘤质控中心肺癌质控专家委员会.中国原发性肺癌规范诊疗质量控制指标（2022版）［J］.中华肿瘤杂志，2022，44（12）：1235-1241.doi：10.3760/cma.j.cn112152-20220418-00266http://dx.doi.org/10.3760/cma.j.cn112152-20220418-00266.

Kristensen LS，Andersen MS，Stagsted LVW，et al.The biogenesis，biology and characterization of circular RNAs［J］.Nat Rev Genet，2019，20（11）：675-691.doi：10.1038/s41576-019-0158-7http://dx.doi.org/10.1038/s41576-019-0158-7.

Li B，Zhu L，Lu C，et al.circNDUFB2 inhibits non-small cell lung cancer progression via destabilizing IGF2BPs and activating anti-tumor immunity［J］.Nat Commun，2021，12（1）：295.doi：10.1038/s41467-020-20527-zhttp://dx.doi.org/10.1038/s41467-020-20527-z.

Vo JN，Cieslik M，Zhang Y，et al.The landscape of circular RNA in cancer［J］.Cell，2019，176（4）：869-881.e13.doi：10.1016/j.cell.2018.12.021http://dx.doi.org/10.1016/j.cell.2018.12.021.

Friedman RC，Farh KK，Burge CB，et al.Most mammalian mRNAs are conserved targets of microRNAs［J］.Genome Res，2009，19（1）：92-105.doi：10.1101/gr.082701.108http://dx.doi.org/10.1101/gr.082701.108.

Quiñones-Díaz BI，Reyes-González JM，Sánchez-Guzmán V，et al.MicroRNA-18a-5p suppresses tumor growth via targeting matrix metalloproteinase-3 in cisplatin-resistant ovarian cancer［J］.Front Oncol，2020，10：602670.doi：10.3389/fonc.2020.602670http://dx.doi.org/10.3389/fonc.2020.602670.

Bray F，Ferlay J，Soerjomataram I，et al.Global cancer statistics 2018：GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries［J］.CA Cancer J Clin，2018，68（6）：394-424.doi：10.3322/caac.21492http://dx.doi.org/10.3322/caac.21492.

Bade BC，Dela Cruz CS.Lung cancer 2020：epidemiology，etiology，and prevention［J］.Clin Chest Med，2020，41（1）：1-24.doi：10.1016/j.ccm.2019.10.001http://dx.doi.org/10.1016/j.ccm.2019.10.001.

Li MY，Liu LZ，Dong M.Progress on pivotal role and application of exosome in lung cancer carcinogenesis，diagnosis，therapy and prognosis［J］.Mol Cancer，2021，20（1）：22.doi：10.1186/s12943-021-01312-yhttp://dx.doi.org/10.1186/s12943-021-01312-y.

Chen L，Nan A，Zhang N，et al.Circular RNA 100146 functions as an oncogene through direct binding to miR-361-3p and miR-615-5p in non-small cell lung cancer［J］.Mol Cancer，2019，18（1）：13.doi：10.1186/s12943-019-0943-0http://dx.doi.org/10.1186/s12943-019-0943-0.

Li P，Chen H，Chen S，et al.Circular RNA 0000096 affects cell growth and migration in gastric cancer［J］.Br J Cancer，2017，116（5）：626-633.doi：10.1038/bjc.2016.451http://dx.doi.org/10.1038/bjc.2016.451.

Wang J，Zhao X，Wang Y，et al.circRNA-002178 act as a ceRNA to promote PDL1/PD1 expression in lung adenocarcinoma［J］.Cell Death Dis，2020，11（1）：32.doi：10.1038/s41419-020-2230-9http://dx.doi.org/10.1038/s41419-020-2230-9.

Liang Y，Wang H，Chen B，et al.circDCUN1D4 suppresses tumor metastasis and glycolysis in lung adenocarcinoma by stabilizing TXNIP expression［J］.Mol Ther Nucleic Acids，2020，23：355-368.doi：10.1016/j.omtn.2020.11.012http://dx.doi.org/10.1016/j.omtn.2020.11.012.

冯涛，肖向茜，盛望.miRNA在肺癌及肺癌耐药中的作用机制及治疗的研究进展［J］.医学综述，2018，24（1）：61-65.doi：10.3969/j.issn.1006-2084.2018.01.012http://dx.doi.org/10.3969/j.issn.1006-2084.2018.01.012.

Cui M，Qu F，Wang L，et al.MiR-18a-5p facilitates progression of hepatocellular carcinoma by targeting CPEB3［J］.Technol Cancer Res Treat，2021，20：15330338211043976.doi：10.1177/15330 338211043976http://dx.doi.org/10.1177/15330338211043976.

Guo Y，Shi W，Fang R.miR-18a-5p promotes melanoma cell proliferation and inhibits apoptosis and autophagy by targeting EPHA7 signaling［J］.Mol Med Rep，2021，23（1）：79.doi：10.3892/mmr.2020.11717http://dx.doi.org/10.3892/mmr.2020.11717.

Gao S，Zhu D，Zhu J，et al.miR-18a-5p targets FBP1 to promote proliferation，migration，and invasion of liver cancer cells and inhibit cell apoptosis［J］.Comput Math Methods Med，2021，2021：3334065.doi：10.1155/2021/3334065http://dx.doi.org/10.1155/2021/3334065.

Zhang J，Wang J，Xing H，et al.Down-regulation of FBP1 by ZEB1-mediated repression confers to growth and invasion in lung cancer cells［J］.Mol Cell Biochem，2016，411（1/2）：331-340.doi：10.1007/s11010-015-2595-8http://dx.doi.org/10.1007/s11010-015-2595-8.

Zhang Y，Lv C，Dong Y，et al.Aspirin-targeted PD-L1 in lung cancer growth inhibition［J］.Thorac Cancer，2020，11（6）：1587-1593.doi：10.1111/1759-7714.13433http://dx.doi.org/10.1111/1759-7714.13433.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Role of lncRNA RMRP in the proliferation and apoptosis of endometrial carcinoma cells through JAK/STAT signaling pathway

Ferulic acid inhibits the progression of T-cell acute lymphoblastic leukemia by regulating PTEN/PI3K/AKT signaling pathway

Midazolam inhibits proliferation, migration and induces apoptosis of osteosarcoma cells

Research progress of long non-coding RNAs in the regulation of intervertebral disc degeneration

Study in L-carnosine on the proliferation and apoptosis of human hepatocellular carcinoma HepG2 cells

Related Author

FANG Qiu-man

DENG Qing-chun

ZHOU Xiao-fei

HUANG Cong-mei

LI Jing-ru

LI Zhong-xia

NIU Ning-ning

QIAO Yuan

Related Institution

Department of Gynecology，Second Affiliated Hospital of Hainan Medical College

Department of Emergency，First Affiliated Hospital of Hebei North University

Second Department of Anesthesiology， Weifang Hospital of Traditional Chinese Medicine

Department of Orthopedics， Affiliated People's Hospital of Inner Mongolia Medical University

School of Basic Medicine， Inner Mongolia Medical University

⁰