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Analysis of Lncrna-Mirna Interactions in Esophageal Squamous Cell Carcinoma

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DOI: 10.23977/medsc.2021.020104 | Downloads: 3 | Views: 60

Author(s)

Ke shun 1, Lu jun 1, Li rui-chao 2, Wang jing 3, Fang ming-hao 1

Affiliation(s)

1 Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
2 Department of General Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, China
3 Department of Clinical Oncology, Remin Hospital of Wuhan University, Wuhan 430071, China

Corresponding Author

Fang ming-hao

ABSTRACT

objective: The study identify hub genes and vital signal pathways by integrated bioinformatics analysis of GEO and TCGA, in order to obtain new prognostic markers for esophageal squamous cell carcinoma. Method: We use R package Limma (chip data) or edgeR[12] (sequencing data) to calculate the differentially expressed mRNA and lncRNA between GEO esophageal squamous cell carcinoma dataset (GSE23400, GSE38129) and TCGA esophageal squamous cell carcinoma dataset. The genes with significant mean difference (ANOVA) (P value =<0.05) in all samples were analyzed by PCA. According to the correlation between lncRNA and mRNA expression, Cytoscape v3.7 was used to construct lncRNA-mRNA network. We construct a PPI network for the most tightly regulated mRNA and lncRNA by the string online tool . Use Cytoscapev3.7 to screen out the hub genes (here, select the top 10 genes with greater connectivity). GO and KEGG enrichment analysis for hub gene. Based on TCGA clinical data, clinical prognostic analysis of the hub genes of the selected COL protein family was performed. Results: We found that lncRNA-RP11-863P13.3,RP11-576I22.2,CTD-2171N6.1 could co-regulate the up-regulation of 16 genes such as MMP11, THY1, and down-regulated lncRNA is the closest to gene regulation is MAMDC2- AS1 interacts with 19 genes including FHL1 and TGFBR3. We determined that COL5A2, COL3A1, COL1A1 and other hub genes are most affected in the lncRNA-mRNA regulatory network of esophageal squamous cell carcinoma. The GO and kegg enrichment analysis of COL family genes showed that extracellular matrix organization, fibrillar collagen trimer, and extracellular matrix structural enrichment scores were the highest. Survival analysis showed that high expression of the four genes COL1A1, COL1A2, COL3A1, COL5A2 can significantly shorten the disease-free survival period of esophageal squamous cell carcinoma, and the prognosis of patients becomes worse. Conclusion: lncRNA-RP11-863P13.3, RP11-576I22.2, CTD-2171N6.1 may promote changes in ECM traits by up-regulating COL1A1,COL1A2,COL3A1,COL5A2, leading to poor prognosis in patients with esophageal squamous cell carcinoma, and could be potential biomarkers for ESCC patients’s prognosis.

KEYWORDS

Esophageal squamous cell carcinoma(escc), Col, Lncrna, Protein-protein interaction network(ppin), Hub gene

CITE THIS PAPER

Ke shun, Lu jun, Li rui-chao, Wang jing, Fang ming-hao. Analysis of Lncrna-Mirna Interactions in Esophageal Squamous Cell Carcinoma. MEDS Clinical Medicine (2021) 2: 15-26. DOI: http://dx.doi.org/10.23977/medsc.2021.020104.

REFERENCES

[1] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020 Jan;70(1):7-30.
[2] Sudo K, Kato K, Matsuzaki J, Boku N, Abe S, Saito Y, Daiko H, Takizawa S, Aoki Y, Sakamoto H, Niida S, Takeshita F, Fukuda T, Ochiya T. Development and Validation of an Esophageal Squamous Cell Carcinoma Detection Model by Large-Scale MicroRNA Profiling. JAMA Netw Open. 2019 May 3;2(5):e194573.
[3] Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018. 68(6): p. 394-424.
[4] Maret-Ouda J, Wahlin K, Artama M, Brusselaers N, Färkkilä M, Lynge E, Mattsson F, Pukkala E, Romundstad P, Tryggvadóttir L, von Euler-Chelpin M, Lagergren J. Risk of Esophageal Adenocarcinoma After Antireflux Surgery in Patients With Gastroesophageal Reflux Disease in the Nordic Countries. JAMA Oncol. 2018 Nov 1;4(11):1576-1582.
[5] Suntharalingam M, Winter K, Ilson D, Dicker AP, Kachnic L, Konski A, Chakravarthy AB, Anker CJ, Thakrar H, Horiba N, Dubey A, Greenberger JS, Raben A, Giguere J, Roof K, Videtic G, Pollock J, Safran H, Crane CH. Effect of the Addition of Cetuximab to Paclitaxel, Cisplatin, and Radiation Therapy for Patients With Esophageal Cancer: The NRG Oncology RTOG 0436 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2017 Nov 1;3(11):1520-1528.
[6] Liu HT, Liu S, Liu L, Ma RR, Gao P. EGR1-Mediated Transcription of lncRNA-HNF1A-AS1 Promotes Cell-Cycle Progression in Gastric Cancer. Cancer Res. 2018 Oct 15;78(20):5877-5890.
[7] Ke Shun., Li Rui-Chao., Lu Jun., Meng Fan-Kai., Feng Yi-Kuan., Fang Ming-Hao.(2017). MicroRNA-192 regulates cell proliferation and cell cycle transition in acute myeloid leukemia via interaction with CCNT2. Int. J. Hematol., 106(2), 258-265. doi:10.1007/s12185-017-2232-2.
[8] Ke Shun., Li Rui-Chao., Meng Fan-Kai., Fang Ming-Hao.(2018). NKILA inhibits NF-κB signaling and suppresses tumor metastasis. Aging (Albany NY), 10(1), 56-71. doi:10.18632/aging.101359.
[9] Li Rui-Chao., Ke Shun., Meng Fan-Kai., Lu Jun., Zou Xiao-Jing., He Zhi-Gang., Wang Weng-Feng., Fang Ming-Hao.(2018). CiRS-7 promotes growth and metastasis of esophageal squamous cell carcinoma via regulation of miR-7/HOXB13. Cell Death Dis, 9(8), 838. doi:10.1038/s41419-018-0852-y.
[10] Ritchie, M.E., et al., limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res, 2015.
[11] Wang, Juan et al. TransmiR: a transcription factor-microRNA regulation database. Nucleic acids research vol. 38,Database issue (2010): D119-22. doi:10.1093/nar/gkp803
[12] Robinson, Mark D et al. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics (Oxford, England) vol. 26,1 (2010): 139-40. doi:10.1093/bioinformatics/btp616
[13] Shannon, P., et al., Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res, 2003. 13(11): p. 2498-504.
[14] von Mering, C., et al., STRING: a database of predicted functional associations between proteins. Nucleic Acids Res, 2003. 31(1): p. 258-61.
[15] He, X. and J. Zhang, Why do hubs tend to be essential in protein networks? PLoS Genet, 2006. 2(6): p. e88.
[16] Ashburner, M., et al., Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet, 2000. 25(1): p. 25-9.
[17] Kanehisa, M. and S. Goto, KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res, 2000. 28(1): p. 27-30.
[18] Langfelder, P., Horvath, S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics 9, 559 (2008) doi:10.1186/1471-2105-9-559.
[19] Gu JX, Zhang X, Miao RC, Xiang XH, Fu YN, Zhang JY, et al. Six-long non-coding RNA signature predicts recurrence-free survival in hepatocellular carcinoma. World J Gastroenterol. (2019) 25:220–32. doi: 10.3748/wjg.v25.i2.220.
[20] Wu Y, Wang PS, Wang BG, Xu L, Fang WX, Che XF, et al. Genomewide identification of a novel six-LncRNA signature to improve prognosis prediction in resectable hepatocellular carcinoma. Cancer Med. (2018) 7:6219–33. doi: 10.1002/cam4.1854.
[21] Shi Yue., Duan Zipeng., Zhang Xun., Zhang Xiaotian., Wang Guoqing., Li Fan.(2019). Down-regulation of the let-7i facilitates gastric cancer invasion and metastasis by targeting COL1A1. Protein Cell, 10(2), 143-148. doi:10.1007/s13238-018-0550-7.
[22] Zeng Wenfeng., Yan Yan., Zhang Fayun., Zhang Chunling., Liang Wei.(2013). Chrysin promotes osteogenic differentiation via ERK/MAPK activation. Protein Cell, 4(7), 539-47. doi:10.1007/s13238-013-3003-3.
[23] Maegdefessel Lars., Azuma Junya., Toh Ryuji., Merk Denis R., Deng Alicia., Chin Jocelyn T., Raaz Uwe., Schoelmerich Anke M., Raiesdana Azad., Leeper Nicholas J., McConnell Michael V., Dalman Ronald L., Spin Joshua M., Tsao Philip S.(2012). Inhibition of microRNA-29b reduces murine abdominal aortic aneurysm development. J. Clin. Invest., 122(2), 497-506. doi:10.1172/JCI61598.
[24] Jia Rui., Wang Changli.(2020). MiR-29b-3p Reverses Cisplatin Resistance by Targeting COL1A1 in Non-Small-Cell Lung Cancer A549/DDP Cells. Cancer Manag Res, 12(undefined), 2559-2566. doi:10.2147/CMAR.S246625.
[25] Klaassens M., Reinstein E., Hilhorst-Hofstee Y., Schrander J J P., Malfait F., Staal H., ten Have L C., Blaauw J., Roggeveen H C J., Krakow D., De Paepe A., van Steensel M A  M., Pals G., Graham J M., Schrander-Stumpel C T R M.(2012). Ehlers-Danlos arthrochalasia type (VIIA-B)--expanding the phenotype: from prenatal life through adulthood. Clin. Genet., 82(2), 121-30. doi:10.1111/j.1399-0004.2011.01758.x.
[26] Zhytnik Lidiia., Maasalu Katre., Reimand Tiia., Duy Binh Ho., Kõks Sulev., Märtson Aare.(2020). Inter- and Intrafamilial Phenotypic Variability in Individuals with Collagen-Related Osteogenesis Imperfecta. Clin Transl Sci, undefined(undefined), undefined. doi:10.1111/cts.12783.
[27] Chapman Teresa., Menashe Sarah J., Taragin Benjamin H.(2020). Radiographic overlap of recurrent Caffey disease and chronic recurrent multifocal osteomyelitis (CRMO) with considerations of molecular origins. Pediatr Radiol, 50(5), 618-627. doi:10.1007/s00247-019-04590-3.
[28] Jen Hsin-Wei., Gu De-Leung., Lang Yaw-Dong., Jou Yuh-Shan.(2020). PSPC1 Potentiates IGF1R Expression to Augment Cell Adhesion and Motility. Cells, 9(6), undefined. doi:10.3390/cells9061490.
[29] Fujii Hideki., Kawada Norifumi., Japan Study Group Of Nafld Jsg-Nafld .(2020). The Role of Insulin Resistance and Diabetes in Nonalcoholic Fatty Liver Disease. Int J Mol Sci, 21(11), undefined. doi:10.3390/ijms21113863.
[30] Reszegi Andrea., Horváth Zsolt., Fehér Hajnalka., Wichmann Barnabás., Tátrai Péter., Kovalszky Ilona., Baghy Kornélia.(2020). Protective Role of Decorin in Primary Hepatocellular Carcinoma. Front Oncol, 10(undefined), 645. doi:10.3389/fonc.2020.00645.
[31] Agioutantis Panagiotis C., Kotsikoris Vasilios., Kolisis Fragiskos N., Loutrari Heleni.(2020). RNA-seq data analysis of stimulated hepatocellular carcinoma cells treated with epigallocatechin gallate and fisetin reveals target genes and action mechanisms. Comput Struct Biotechnol J, 18(undefined), 686-695. doi:10.1016/j.csbj.2020.03.006.
[32] Li Yanan., Wang Jun., Song Kun., Liu Shuangqing., Zhang Huilei., Wang Fei., Ni Chen., Zhai Wenlong., Liang Jialu., Qin Zhihai., Zhang Jinhua.(2020). S100A4 promotes hepatocellular carcinogenesis by intensifying fibrosis-associated cancer cell stemness. Oncoimmunology, 9(1), 1725355. doi:10.1080/2162402X.2020.1725355.
[33] Kato Mitsuo., Natarajan Rama.(2019). Epigenetics and epigenomics in diabetic kidney disease and metabolic memory. Nat Rev Nephrol, 15(6), 327-345. doi:10.1038/s41581-019-0135-6.
[34] Anastasiadou Eleni., Jacob Leni S., Slack Frank J.(2018). Non-coding RNA networks in cancer. Nat. Rev. Cancer, 18(1), 5-18. doi:10.1038/nrc.2017.99.
[35] Du Zhou., Fei Teng., Verhaak Roel G W., Su Zhen., Zhang Yong., Brown Myles., Chen Yiwen., Liu X Shirley.(2013). Integrative genomic analyses reveal clinically relevant long noncoding RNAs in human cancer. Nat. Struct. Mol. Biol., 20(7), 908-13. doi:10.1038/nsmb.2591.
[36] Ni W, Zhang Y, Zhan Z, Ye F, Liang Y, Huang J, Chen K, Chen L, Ding Y. A novel lncRNA uc.134 represses hepatocellular carcinoma progression by inhibiting CUL4A-mediated ubiquitination of LATS1. J Hematol Oncol. 2017 Apr 19;10(1):91.
[37] Tang J, Yan T, Bao Y, Shen C, Yu C, Zhu X, Tian X, Guo F, Liang Q, Liu Q, Zhong M, Chen J, Ge Z, Li X, Chen X, Cui Y, Chen Y, Zou W, Chen H, Hong J, Fang JY. LncRNA GLCC1 promotes colorectal carcinogenesis and glucose metabolism by stabilizing c-Myc. Nat Commun. 2019 Aug 2;10(1):3499.
[38] Liu HT, Liu S, Liu L, Ma RR, Gao P. EGR1-Mediated Transcription of lncRNA-HNF1A-AS1 Promotes Cell-Cycle Progression in Gastric Cancer. Cancer Res. 2018 Oct 15;78(20):5877-5890.

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