Involvement of miRNA target genes in esophageal squamous cell carcinoma through ubiquitination based on GEO database

doi:10.3969/j.issn.1674-8115.2022.04.008

Abstract

Abstract:

objective·To screen new potential pathogenic genes in the course of esophageal squamous cell carcinoma.

Methods

·The data of miRNA chips GSE122497 and GSE164174 were obtained by GEO database. The differential mirnas of esophageal cancer patients and healthy people were screened by GEO2R, and the intersection was obtained by Venn Diagram Webtool. Target Scan tool and DIANATOOLS tool were used to predict the target genes of differential miRNA, and the intersection of predicted target genes of the two tools was used for gene function analysis. The protein interactions of target genes were analyzed by using STRING tool and Hub genes were selected.

Results

·① A total of 108 differential miRNAs were detected in the chip. ② After taking the intersection of Target Scan tool and DIANATOOLS tool, there were 1 354 different target genes. ③Gene Ontology (GO) analysis showed that gene functions of differential target genes were significantly enriched in biological processes such as DNA template transcriptional regulation and RNA polymerase Ⅱ promoter transcriptional regulation, as well as RNA polymerase Ⅱ core promoter proximal sequence specific DNA binding, protein binding, metal ion binding and other molecular functions. It mainly existed in nucleus, cytoplasm, cytoplasm and other cellular components. In descending order of the number of enriched genes, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the above genes were significantly enriched in tumor pathway, MAPK signaling pathway, stem cell pluripotency regulation signaling pathway, etc. ④ There were 1 326 nodes and 2 300 edges in the protein interaction network, and the average node connectivity was 3.47. The selected Hub genes were SMAD specific E3 ubiquitin protein ligase 2 (SMURF2), β-transducin repeat containing E3 ubiquitin protein ligase (BTRC), SMAD specific E3 ubiquitin protein ligase 1 (SMURF 1), ubiquitin conjugating enzyme E2 D1 (UBE2D1), and cullin 2 (CUL2). Previous studies have shown that the above genes are related to ubiquitination.

Conclusion

·SMURF2, BTRC, SMURF1, UBE2D1 and CUL2 genes screened from GEO database may be involved in the disease process of esophageal squamous cell carcinoma through the ubiquitin of targeted regulatory proteins.

Key words: esophageal squamous cell carcinoma, GEO database, ubiquitin, bioinformatics

CLC Number:

R735.1

JIN Bu, YUAN Ying, CHEN Wanyu, XU Hudong, HUANG Xiaolei, HE Jialu, YU Hong. Involvement of miRNA target genes in esophageal squamous cell carcinoma through ubiquitination based on GEO database[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(4): 464-471.

Figures/Tables 4

TrendMD

References 23

1	BREGNI G, BECK B. Toward targeted therapies in oesophageal cancers: an overview [J]. Cancers (Basel), 2022, 14(6): 1522.
2	PARKIN D M. Global cancer statistics in the year 2000 [J]. Lancet Oncol, 2001, 2(9): 533-43.
3	TRAN G D, SUN X D, ABNET C C, et al. Prospective study of risk factors for esophageal and gastric cancers in the Linxian general population trial cohort in China [J]. Int J Cancer, 2005, 113(3): 456-463.
4	SONG Y, LI L, OU Y, et al. Identification of genomic alterations in oesophageal squamous cell cancer [J]. Nature, 2014, 509(7498): 91-95.
5	KANO M, SEKI N, KIKKAWA N, et al. miR-145, miR-133a and miR-133b: tumor-suppressive miRNAs target FSCN1 in esophageal squamous cell carcinoma [J]. Int J Cancer, 2010, 127(12): 2804-2814.
6	YANG L, ZHOU W, LIN H. Posttranslational modifications of smurfs: emerging regulation in cancer [J]. Front Oncol, 2020, 10:610663.
7	ZHANG Y, DING H, WANG X, et al. MK2 promotes Tfcp2l1 degradation via β-TrCP ubiquitin ligase to regulate mouse embryonic stem cell self-renewal [J]. Cell Rep, 2021, 37(5): 109949.
8	XIE H, HE Y, WU Y, et al. Silencing of UBE2D1 inhibited cell migration in gastric cancer, decreasing ubiquitination of SMAD4 [J]. Infect Agent Cancer, 2021, 16(1): 63.
9	WANG K, LIU X. Determining the effects of neddylation on cullin-RING ligase-dependent protein ubiquitination [J]. Curr Protoc, 2022, 2(3): e401.
10	KOGANTI P, LEVY-COHEN G, BLANK M. Smurfs in protein homeostasis, signaling, and cancer [J]. Front Oncol, 2018, 8: 295.
11	刘朦迪, 潘漪莲, 朱晓娜, 等. FBXO22调控凋亡诱导因子的分子机制及其在肿瘤细胞凋亡中的作用 [J]. 上海交通大学学报(医学版), 2021, 41(4): 427-33.
	LIU M D, PAN Y L, ZHU X N, et al. FBXO22 regulates the molecular mechanism of apoptosis inducers and its role in tumor cell apoptosis[J]. J Shanghai Jiao Tong Univ (Med Sci), 2021, 41(04): 427-433.
12	KOMANDER D, RAPE M. The ubiquitin code [J]. Annu Rev Biochem, 2012, 81: 203-229.
13	GUO X, WANG X F. Signaling cross-talk between TGF-β/BMP and other pathways [J]. Cell Res, 2009, 19(1): 71-88.
14	DEMPKE W C M, FENCHEL K, UCIECHOWSKI P, et al. Targeting developmental pathways: the achilles heel of cancer? [J]. Oncology, 2017, 93(4): 213-223.
15	HAUPT Y, MAYA R, KAZAZ A, et al. Mdm2 promotes the rapid degradation of p53 [J]. Nature, 1997, 387(6630): 296-299.
16	KWEI K A, SHAIN A H, BAIR R, et al. SMURF1 amplification promotes invasiveness in pancreatic cancer [J]. PLoS One, 2011, 6(8): e23924.
17	FUKUCHI M, FUKAI Y, MASUDA N, et al. High-level expression of the Smad ubiquitin ligase Smurf2 correlates with poor prognosis in patients with esophageal squamous cell carcinoma [J]. Cancer Res, 2002, 62(24): 7162-7165.
18	ZHONG J, OGURA K, WANG Z, et al. Degradation of the transcription factor Twist, an oncoprotein that promotes cancer metastasis [J]. Discov Med, 2013, 15(80): 7-15.
19	ORIAN A, GONEN H, BERCOVICH B, et al. SCF(β)(-TrCP) ubiquitin ligase-mediated processing of NF-κB p105 requires phosphorylation of its C-terminus by IκB kinase [J]. EMBO J, 2000, 19(11): 2580-2591.
20	ZHANG B, ZHANG Z, LI L, et al. TSPAN15 interacts with BTRC to promote oesophageal squamous cell carcinoma metastasis via activating NF-κB signaling [J]. Nat Commun, 2018, 9(1): 1423.
21	ZHOU C, BI F, YUAN J, et al. Gain of UBE2D1 facilitates hepatocellular carcinoma progression and is associated with DNA damage caused by continuous IL-6 [J]. J Exp Clin Cancer Res, 2018, 37(1): 290.
22	JACOBSEN A, BOSCH L J W, MARTENS-DE KEMP S R, et al. Aurora kinase A (AURKA) interaction with Wnt and Ras-MAPK signalling pathways in colorectal cancer [J]. Sci Rep, 2018, 8(1): 7522.
23	METZGER R, HEUKAMP L, DREBBER U, et al. CUL2 and STK11 as novel response-predictive genes for neoadjuvant radiochemotherapy in esophageal cancer [J]. Pharmacogenomics, 2010, 11(8): 1105-1113.

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