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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

28卷

期数:

2022年01期

页码:

8-14

栏目:

生物信息学专题

出版日期:

2022-01-20

文章信息/Info

Title:

Identification of key genes in cervical cancer progression by integrated bioinformatics analysis

文章编号:

1006-8147（2022）01-0008-07

作者:

刘玉林; 臧玉琴; 王颖梅; 薛凤霞

（天津医科大学总医院妇产科；天津市女性生殖健康与优生重点实验室，天津 300052）

Author(s):

LIU Yu-lin; ZANG Yu-qin; WANG Ying-mei; XUE Feng-xia

（Department of Gynecology and Obstetrics，The General Hospital，Tianjin Medical University；Tianjin Key Laboratory of Female Reproductive Health and Eugenics， Tianjin 300052，China ）

关键词:

宫颈癌; 生物信息学分析; 差异表达基因; 差异表达miRNA; 蛋白质-蛋白质相互作用网络; miRNA-靶基因调控网络

Keywords:

cervical cancer;  bioinformatics analysis; differentially expressed gene;  differentially expressed miRNA;  protein-protein interaction network;  miRNA-target regulatory network

分类号:

R737.33

DOI:

-

文献标志码:

A

摘要:

目的：通过生物信息学分析的方法，筛选宫颈癌进展中的关键基因，寻找潜在的分子标志物和治疗靶点。方法：在GEO（Gene Expression Omnibus）数据库中检索宫颈癌进展相关的mRNA和miRNA基因芯片数据，借助GEO2R分析差异表达基因（DEG）和差异表达miRNA（DEM），进行富集分析以及构建蛋白质-蛋白质相互作用（PPI）网络和miRNA-靶基因调控网络。结果：共筛选出250个DEG和166个DEM，并构建出由123个节点（node）和283项互相作用（edge）构成的PPI网络以及由66个节点和137个相互作用构成的miRNA-靶基因调控网络。经分析，ATAD2、SMC4和POLQ基因不仅是筛选出的表达上调的DEG，而且是PPI网络中枢纽蛋白的编码基因，并在miRNA-靶基因调控网络中同时受DEM—miR-20A、miR-20B、miR-106B和miR-17-5P的调控。结论：ATAD2、SMC4和POLQ基因可能在宫颈癌进展过程中发挥着重要作用。

Abstract:

Objective： To identify the key genes in cervical cancer progression by integrated bioinformatics analysis to search for potential biomarkers and therapeutic targets. Methods：The mRNA and miRNA microarray datasets related to the progression of cervical cancer were searched on the GEO（the Gene Expression Omnibus） database and differentially expressed gene（DEG） and differentially expressedmiRNA （DEM） were analyzed by GEO2R. Then， the functional enrichment analyses， protein-protein interaction（PPI） network and miRNA-target regulatory network construction were conducted. Results:Totally， 250 DEGs and 166 DEMs in the progression of cervical cancer were screened out，and a PPI network composed of 123 nodes and 283 edges and a miRNA-target regulatory network composed of 66 nodes and 137 edges were constructed. Based on a series of analyses， the genes ATAD2， SMC4 and POLQ were not only identified as the overexpressed DEGs， but also the coding genes of hub proteins in the PPI network and regulated by the DEMs，miR-20A，miR-20B，miR-106B and miR-17-5P in the miRNA-target gene regulatory network. Conclusion: ATAD2， SMC4 and POLQ genes may play important roles in the progression of cervical cancer.

参考文献/References:

[1] COHEN P A，JHINGRAN A，OAKNIN A，et al. Cervical cancer[J].Lancet，2019，393（10167）：169-182.
[2] YI Y，LIU Y，WU W，et al. Reconstruction and analysis of circRNA miRNA mRNA network in the pathology of cervical cancer[J]. Oncol Rep，2019，41（4）：2209-2225.
[3] ZHENG L，LI T，ZHANG Y，et al. Oncogene ATAD2 promotes cell proliferation，invasion and migration in cervical cancer[J]. Oncol Rep，2015，33（5）：2337-2344.
[4] THADANI R，KAMENZ J，HEEGER S，et al. Cell-cycle regulation of dynamic chromosome association of the condensin complex[J].Cell Rep，2018，23（8）：2308-2317.
[5] PALOU R，DHANARAMAN T，MARRAKCHI R，et al. Condensin ATPase motifs contribute differentially to the maintenance of chromosome morphology and genome stability[J]. PLoS Biol，2018，16（6）：e2003980.
[6] HUANG K，JIA J，WU C，et al. Ribosomal RNA gene transcription mediated by the master genome regulator protein CCCTC-binding factor （CTCF） is negatively regulated by the condensin complex[J]. J Biol Chem，2013，288（36）：26067-26077.
[7] ZHAO SG，EVANS JR，KOTHARI V，et al. The landscape of prognostic outlier genes in high-risk prostate cancer[J]. Clin Cancer Res，2016，22（7）：1777-1786.
[8] WANG Z，SONG Y，LI S，et al. DNA polymerase theta（POLQ） is important for repair of DNA double-strand breaks caused by fork collapse[J]. J Biol Chem，2019，294（11）：3909-3919.
[9] HONEGGER A，SCHILLING D，BASTIAN S，et al. Dependence of intracellular and exosomal microRNAs on viral E6/E7 oncogene expression in HPV-positive tumor cells[J]. PLoS Pathog，2015，1（3）：e1004712.
[10] LIU X. Up-regulation of miR-20a by HPV16 E6 exerts growth-promoting effects by targeting PDCD6 in cervical carcinoma cells[J].Biomed Pharmacother，2018，102：996-1002.
[11] ZHENG Z M，WANG X. Regulation of cellular miRNA expression by human papillomaviruses[J]. Biochim Biophys Acta，2011，1809（11/12）：668-677.
[12] CHENG Y，GUO Y，ZHANG Y，et al. MicroRNA-106b is involved in transforming growth factor beta1-induced cell migration by targeting disabled homolog 2 in cervical carcinoma[J]. J Exp Clin Cancer Res，2016，35：11.
[13] LI M Y，HU X X. Meta-analysis of microRNA expression profiling studies in human cervical cancer[J]. Med Oncol，2015，32（6）：510.
[14] MA D，ZHANG Y Y，GUO Y L，et al. Profiling of microRNA-mRNA reveals roles of microRNAs in cervical cancer[J]. Chin Med J（Engl），2012，125（23）：4270-4276
[15] KANG H W，WANG F，WEI Q，et al. miR-20a promotes migration and invasion by regulating TNKS2 in human cervical cancer cells[J].FEBS Lett，2012，586（6）：897-904.
[16] XIONG Y，SUN F，DONG P，et al. iASPP induces EMT and cisplatin resistance in human cervical cancer through miR-20a-FBXL5/BTG3 signaling[J]. J Exp Clin Cancer Res，2017，36（1）：48.
[17] ZHAO S，YAO D，CHEN J，et al. MiR-20a promotes cervical cancer proliferation and metastasis in vitro and in vivo[J]. PLoS One，2015， 10（3）：e0120905.
[18] ZHOU Q，DONG J，LUO R，et al. MicroRNA-20a regulates cell proliferation，apoptosis and autophagy by targeting thrombospondin 2 in cervical cancer[J]. Eur J Pharmacol，2019，844：102-109.
[19] ZHU S Y，WU Q Y，ZHANG C X，et al. miR-20a inhibits the killing effect of natural killer cells to cervical cancer cells by downregulating RUNX1[J]. Biochem Biophys Res Commun，2018，505（1）：309-316.
[20] CAI N，HU L，XIE Y，et al. MiR-17-5p promotes cervical cancer cell proliferation and metastasis by targeting transforming growth factor-beta receptor 2[J]. Eur Rev Med Pharmacol Sci，2018，22（7）：1899-1906.

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备注/Memo

备注/Memo:

基金项目 国家自然科学基金（81972448）；天津市科委基金（20JCZDJC00330）
作者简介 刘玉林（1993-），女，硕士在读，研究方向：子宫内膜癌的基础与临床研究；通信作者：薛凤霞，E-mail：fengxiaxue1962@tmu.edu.cn。

常用功能

更新日期/Last Update: 2022-01-20