[1]沈运涛,蔡笃雄.肺鳞状细胞癌组织中LncRNA MIR205HG 的表达及对癌细胞增殖克隆的影响和机制研究[J].现代检验医学杂志,2022,37(04):30-34+58.[doi:10.3969/j.issn.1671-7414.2022.04.006]
 SHEN Yun-tao,CAI Du-Xiong.Expression of LncRNA MIR205HG in Squamous Cell Lung Carcinoma and Its Effect on Cell Proliferation and Cloning and Mechanism[J].Journal of Modern Laboratory Medicine,2022,37(04):30-34+58.[doi:10.3969/j.issn.1671-7414.2022.04.006]
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肺鳞状细胞癌组织中LncRNA MIR205HG 的表达及对癌细胞增殖克隆的影响和机制研究()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第37卷
期数:
2022年04期
页码:
30-34+58
栏目:
论著
出版日期:
2022-07-15

文章信息/Info

Title:
Expression of LncRNA MIR205HG in Squamous Cell Lung Carcinoma and Its Effect on Cell Proliferation and Cloning and Mechanism
文章编号:
1671-7414(2022)04-030-06
作者:
沈运涛1蔡笃雄2
1. 海口市琼山区妇幼保健院儿科,海口 571100;2. 海南医学院附属医院消化内科,海口 570102
Author(s):
SHEN Yun-tao1 CAI Du-Xiong2
1.Department of Pediatrics, Qiongshan Maternal and Child Health Hospital of Haikou City, Haikou 571100,China;2.Department of Digestive Medicine Affiliated Hospital of Hainan Medical College, Haikou 570102, China
关键词:
长链非编码核糖核酸(LncRNAs)MIR205HG肺鳞状细胞癌
分类号:
R734.2;R730.43
DOI:
10.3969/j.issn.1671-7414.2022.04.006
文献标志码:
A
摘要:
目的 筛选肺鳞状细胞癌(squamous cell lung carcinoma,SQCLC)中差异表达且具有临床意义的潜在靶基因,并探究其在癌组织中的表达及其调控肺鳞状细胞癌发生发展的分子机制。方法 通过临床数据库GEPIA 找出在肺鳞状细胞癌中差异表达的长链非编码RNA(long noncoding RNAs,LncRNAs),进一步筛选出相较于正常肺组织表达差异性最显著的LncRNAs 作为研究目的基因。通过PholyCSF 数据库预测目的基因在肺鳞状细胞癌中发挥功能的形式。通过短发夹RNA(shRNA)介导敲低目的基因表达,利用细胞增殖实验、克隆形成实验验证目的基因在肺鳞状细胞癌发生发展中的重要性;通过分析与目的基因共表达基因参与的信号通路,探索其在肺鳞状细胞癌中发挥功能的潜在分子机制。结果 研究最终选取在肺鳞状细胞癌中显著差异高表达的MIR205HG 作为目的基因进行实验探究。肺鳞状细胞癌组织中MIR205HG 表达显著高于正常肺组织(6.785±0.462 vs 1.084±0.036),差异有统计学意义(t=188.873,P < 0.05),且随着临床分期越高MIR205HG 表达水平越高(P=0.047 2)。MIR205HG 主要通过LncRNA 形式在肺鳞状细胞癌中发挥功能。与shCTL 组(0.988±0.039)相比,shMIR205HG#1 组(0.709±0.032)和shMIR205HG#2 组(0.736±0.026)细胞的增殖率明显降低,差异有统计学意义(F=66.163,P < 0.001)。shMIR205HG#1 组(0.324±0.021)和shMIR205HG#2 组(0.402±0.023)细胞克隆形成速率明显低于shCTL 对照组(1.809±0.019),差异有统计学意义(F=423.093,P < 0.001)。shMIR205HG#1 组(5.988±0.321)和shMIR205HG#2 组(5.702±0.345)细胞中P53 蛋白表达明显高于shCTL 对照组(1.022±0.152),差异有统计学意义(F =285.386,P< 0.001)。shMIR205HG#1 组(3.857±0.362)和shMIR205HG#2 组(3.698±0.314)细胞中下游P21 蛋白表达亦明显高于shCTL 对照组(1.106±0.253),差异有统计学意义(F =73.106,P < 0.001)。结论 lncRNA MIR205HG 在肺鳞状细胞癌中显著高表达,可能通过P53 信号通路参与肺鳞状细胞癌的增殖和克隆形成,可作为肺鳞状细胞癌的潜在药物治疗靶点。
Abstract:
Objective To screen potential target genes with differential expression and clinical significance in squamous cell lung carcinoma(SQCLC), and explore their expression in cancer tissues and the molecular mechanism of regulation of the occurrence and development of SQCLC. Methods Long non coding RNAs(LncRNAs) differentially expressed in SQCLC were identified through the clinical database GEPIA, and the lncRNAs with the most significant difference in expression compared with normal lung tissue were further selected as the target genes. The PholyCSF database was used to predict the functional pattern of the target gene in SQCLC. ShRNA mediated knockdown of target gene expression was used to verify the importance of target gene in the development and development of SQCLC by cell proliferation assay and clone formation assay. By analyzing the signaling pathways involved in the co-expression genes of the target genes, the potential molecular mechanisms of their function in SQCLC were explored. Results Finally, MIR205HG, which was significantly differentially expressed in SQCLC, was selected as the target gene for experimental exploration .The expression of MIR205HG in SQCLC was significantly higher than that in normal lung tissue (6.785±0.462 vs 1.084±0.036), the difference was statistically significant(t=188.873, P < 0.05), and the higher the clinical stage was, the higher the MIR205HG expression level was (P=0.047 2). MIR205HG plays a role in SQCLC mainly through LncRNA form .Compared with the shCTL group (0.988±0.039), the proliferation rate of shMIR205HG#1 group (0.709±0.032) and shMIR205HG#2 group (0.736±0.026) was significantly decreased,the difference was statistically significant(F=66.163, P < 0.001).The rate of cell cloning formation in shMIR205HG#1 group (0.324±0.021) and shMIR205HG#2 group (0.402±0.023) was significantly lower than that in shCTL control group (1.809±0.019) ,the difference was statistically significant(F=423.093, P < 0.001).The expression of P53 protein in shMIR205HG#1 group (5.988±0.321) and shMIR205HG#2 group (5.702±0.345) was significantly higher than that in shCTL control group (1.022± 0.152) ,the difference was statistically significant(F=285.386, P < 0.001).The expression of P21 protein in shMIR205HG#1 group (3.857±0.362) and shMIR205HG#2 group (3.698±0.314) was significantly higher than that in shCTL control group (1.106±0.253),the difference was statistically significant(F=73.106, P < 0.001).Conclusion LncRNA MIR205HG was highly expressed in lung squamous cell carcinoma, and would be involved in the proliferation and cloning of SQCLC through the P53 signaling pathway, which can be used as a potential drug therapy target for lung.

参考文献/References:

[1] SIEGEL R L, MILLER K D, JEMAL A. Cancer statistics, 2019 [J]. CA Cancer J Clin, 2019, 69(1):7-34.
[2] CAO Maomao, CHEN Wanqing. Epidemiology of lung cancer in China[J]. Thoracic Cancer, 2019, 10(1): 3-7.
[3] DONG Ming, GONG Hao, LI Tong, et al. Lymph node metastasis in lung squamous cell carcinoma and identification of metastasis-related genes based on the Cancer Genome Atlas [J]. Cancer Medicine, 2019,8(14): 6280-6294.
[4] 席俊峰, 彭彦才, 马兴聪, 等.Aurora-B 激酶的表达与非小细胞肺癌患者预后及耐药的相关性分析[J].现代检验医学杂志, 2020, 35(6):59-63. XI Junfeng, PENG Yancai, MA Xingcong, et al. Study on the relationship between high expression of aurora-B kinase and drug resistance and prognosis in patients with non-small cell lung cancer [J]. Journal of Modern Laboratory Medicine, 2020, 35(6): 59-63.
[5] YAMAMURA S, IMAI-SUMIDA M, TANAKA Y,et al. Interaction and cross-talk between non-coding RNAs[J]. Cellular and Molecular Life Sciences, 2018,75(3): 467-484.
[6] CARLEVARO-FITA J, LANZ?S A, FEUERBACH L,et al. Cancer lncRNA census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis[J]. Communications Biology, 2020, 3(1): 56.
[7] LIU Chang, LI Yinyan, WEI Minjie, et al. Identification of a novel glycolysis-related gene signature that can predict the survival of patients with lung adenocarcinoma[J]. Cell Cycle (Georgetown, Tex.),2019, 18(5): 568-579.
[8] DASTMALCHI N, SAFARALIZADEH R, NARGESI M M. LncRNAs: Potential novel prognostic and diagnostic biomarkers in colorectal cancer[J]. Current Medicinal Chemistry, 2020, 27(30): 5067-5077.
[9] 闫小妮, 田国祥, 潘振宇, 等. 如何挖掘GEPIA 数据库中研究数据并生成分析结果表达图[J]. 中国循证心血管医学杂志, 2019, 11(5):521-525. YAN Xiaoni, TIAN Guoxiang, PAN Zhenyu, et al. How to research data in the GEPIA database and generate an analysis result graph [J]. Chinese Journal of Evidence-Based Cardiovascular Medicine, 2019, 11(5): 521-525.
[10] MUDGE J M, JUNGREIS I, HUNT T, et al. Discovery of high-confidence human protein-coding genes and exons by whole-genome PhyloCSF helps elucidate 118 GWAS loci[J]. Genome Research, 2019, 29(12): 2073-2087.
[11] WU P, HEINS Z J, MULLER J T, et al. Integration and analysis of CPTAC proteomics data in the context of cancer genomics in the cBioPortal[J]. Molecular & Cellular Proteomics, 2019, 18(9): 1893-1898.
[12] 吴良银, 李文丽, 刘俊.肝细胞癌患者生存预后相关长链非编码RNA(lncRNA) 的生物信息学分析[J].现代检验医学杂志, 2019, 34(4):18-21. WU Liangyin, LI Wenli, LIU Jun. Bioinformatics analysis of long-chain non-coding RNA related to survival and prognosis in patients with hepatocellular carcinoma [J]. Journal of Modern Laboratory Medicine,2019, 34(4): 18-21.
[13] WU Cheng, WEI Yunzhen, ZHU Yinling, et al.Identification of cancer-related potential biomarkers based on lncRNA-pseudogene-mRNA competitive networks[J]. FEBS Letters, 2018, 592(6): 973-986.
[14] YANG Chun, PAN Yong, DENG Shaoping. Downregulation of lncRNA CCAT1 enhances 5-fluorouracil sensitivity in human colon cancer cells[J]. BMC Molecular and Cell Biology, 2019, 20(1): 9.
[15] CHEN Zhaolin, PAN Tingting, JIANG Duochen, et al.The lncRNA-GAS5/miR-221-3p/DKK2 Axis modulates ABCB1-mediated adriamycin resistance of breast cancer via the Wnt/β-catenin signaling pathway[J].Mol Ther Nucleic Acids, 2020 , 19:1434-1448.
[16] ZHANG Y X, YUAN J, GAO Z M, et al. LncRNA TUC338 promotes invasion of lung cancer by activating MAPK pathway[J]. European Review for Medical and Pharmacological Sciences, 2018, 22(2): 443-449.
[17] LI Sen, MEI Zhoufang, HU Haibo, et al. The lncRNA MALAT1 contributes to non-small cell lung cancer development via modulating miR-124/STAT3 axis[J].Journal of Cellular Physiology, 2018, 233(9): 6679-6688.
[18] GUO Dong, WANG Yanli, REN Kewei, et al. Knockdown of lncRNA PVT1 inhibits tumorigenesis in nonsmall-cell lung cancer by regulating miR-497 expression[ J]. Experimental Cell Research, 2018, 362(1):172-179.
[19] ZHAO Chengling, QIAO Chenchen, ZONG Liguo,et al. Long noncoding RNA-CCAT2 promotes the occurrence of non-small cell lung cancer by regulating the Wnt/βcatenin signaling pathway[J]. Oncology Letters, 2018, 16(4): 4600-4606.
[20] LI Yishu, WANG Hongying, HUANG Huijuan. Long non-coding RNA MIR205HG function as a ceRNA to accelerate tumor growth and progression via sponging miR-122-5p in cervical cancer[J]. Biochemical and Biophysical Research Communications, 2019, 514(1):78-85.
[21] DI AGOSTINO S, VALENTI F, SACCONI A, et al.Long non-coding MIR205HG depletes Hsa-miR-590-3p leading to unrestrained proliferation in head and neck squamous cell carcinoma[J]. Theranostics, 2018,8(7): 1850-1868.
[22] GUO Jianlan, GAN Quan, GAN Caibin, et al. LncRNA MIR205HG regulates melanomagenesis via the miR-299-3p/VEGFA axis[J]. Aging, 2021, 13(4): 5297-5311.
[23] SONG J H, TIEU A H, CHENG Yulan, et al. Novel long noncoding RNA miR205HG functions as an esophageal tumor-suppressive hedgehog inhibitor[J].Cancers(Basel), 2021, 13(7): 1707.
[24] LI Hongle, JIA Jinlin, YANG Lijun, et al. LncRNA MIR205HG drives esophageal squamous cell carcinoma progression by regulating miR-214/SOX4 axis[J]. OncoTargets and Therapy, 2020, 13: 13097-13109.
[25] KAST D J, DOMINGUEZ R. Mechanism of IRSp53 inhibition by 14-3-3[J]. Nature Communications, 2019,10(1): 483.

备注/Memo

备注/Memo:
基金项目:海南省重点研发计划项目(ZDYF2018135)。
作者简介:沈运涛(1970-),男,本科,主治医师,研究方向: 呼吸系统、儿科门诊,E-mail:hool1000100@yeah.net。
通讯作者:蔡笃雄,博士学位,研究生导师,主任医师,消化内科科室副主任。
更新日期/Last Update: 1900-01-01