Five genes involved in circular RNA-associated competitive endogenous RNA network correlates with metastasis in papillary thyroid carcinoma

This study aimed to identify potential circular RNA (circRNA), microRNA (miRNA) and mRNA biomarkers as well as their underlying regulatory mechanisms in papillary thyroid carcinoma (PTC). Three microarray datasets from the Gene Expression Omnibus database as well as expression data and clinical phen...

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Autores principales: Jie Qiu, Maolin Sun, Chuanshan Zang, Liwei Jiang, Zuorong Qin, Yan Sun, Mingbo Liu, Wenwei Zhang
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Publicado: AIMS Press 2021
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spelling oai:doaj.org-article:6d0af47319a84b128b555c3c0ee48d932021-11-29T02:57:14ZFive genes involved in circular RNA-associated competitive endogenous RNA network correlates with metastasis in papillary thyroid carcinoma10.3934/mbe.20214441551-0018https://doaj.org/article/6d0af47319a84b128b555c3c0ee48d932021-10-01T00:00:00Zhttps://www.aimspress.com/article/doi/10.3934/mbe.2021444?viewType=HTMLhttps://doaj.org/toc/1551-0018This study aimed to identify potential circular RNA (circRNA), microRNA (miRNA) and mRNA biomarkers as well as their underlying regulatory mechanisms in papillary thyroid carcinoma (PTC). Three microarray datasets from the Gene Expression Omnibus database as well as expression data and clinical phenotype from The Cancer Genome Atlas (TCGA) were downloaded, followed by differential expression, functional enrichment, protein–protein interaction (PPI), and module analyses. The support vector machine (SVM)-recursive feature elimination (RFE) algorithm was used to screen the key circRNAs. Finally, the mRNA-miRNA-circRNA regulatory network and competitive endogenous RNA (ceRNA) network were constructed. The prognostic value and clinical correlations of key mRNAs were investigated using TCGA dataset, and their expression was validated using the UALCAN database. A total of 1039 mRNAs, 18 miRNAs and 137 circRNAs were differentially expressed in patients with PTC. A total of 37 key circRNAs were obtained using the SVM-RFE algorithm, whereas 46 key mRNAs were obtained from significant modules in the PPI network. A total of 11 circRNA-miRNA pairs and 40 miRNA-mRNA pairs were predicted. Based on these interaction pairs, 46 circRNA-miRNA-mRNA regulatory pairs were integrated, of which 8 regulatory pairs in line with the ceRNA hypothesis were obtained, including two circRNAs (circ_0004053 and circ_0028198), three miRNAs (miR-199a-5p, miR-199b-5p, and miR-7-5p), and five mRNAs, namely APOA2, CCL20, LPAR5, MFGE8, and TIMP1. Survival analysis showed that LPAR5 expression was associated with patient survival. APOA2 expression showed significant differences between metastatic and non-metastatic tumors, whereas CCL20, LPAR5, MFGE8 and TIMP1 showed significant differences between metastatic and non-metastatic lymph nodes. Overall, we identified several potential targets and regulatory mechanisms involved in PTC. APOA2, CCL20, LPAR5, MFGE8, and TIMP1 may be correlated with PTC metastasis.Jie QiuMaolin SunChuanshan Zang Liwei JiangZuorong Qin Yan SunMingbo LiuWenwei ZhangAIMS Pressarticlepapillary thyroid carcinomacircular rnascernametastasisBiotechnologyTP248.13-248.65MathematicsQA1-939ENMathematical Biosciences and Engineering, Vol 18, Iss 6, Pp 9016-9032 (2021)
institution DOAJ
collection DOAJ
language EN
topic papillary thyroid carcinoma
circular rnas
cerna
metastasis
Biotechnology
TP248.13-248.65
Mathematics
QA1-939
spellingShingle papillary thyroid carcinoma
circular rnas
cerna
metastasis
Biotechnology
TP248.13-248.65
Mathematics
QA1-939
Jie Qiu
Maolin Sun
Chuanshan Zang
Liwei Jiang
Zuorong Qin
Yan Sun
Mingbo Liu
Wenwei Zhang
Five genes involved in circular RNA-associated competitive endogenous RNA network correlates with metastasis in papillary thyroid carcinoma
description This study aimed to identify potential circular RNA (circRNA), microRNA (miRNA) and mRNA biomarkers as well as their underlying regulatory mechanisms in papillary thyroid carcinoma (PTC). Three microarray datasets from the Gene Expression Omnibus database as well as expression data and clinical phenotype from The Cancer Genome Atlas (TCGA) were downloaded, followed by differential expression, functional enrichment, protein–protein interaction (PPI), and module analyses. The support vector machine (SVM)-recursive feature elimination (RFE) algorithm was used to screen the key circRNAs. Finally, the mRNA-miRNA-circRNA regulatory network and competitive endogenous RNA (ceRNA) network were constructed. The prognostic value and clinical correlations of key mRNAs were investigated using TCGA dataset, and their expression was validated using the UALCAN database. A total of 1039 mRNAs, 18 miRNAs and 137 circRNAs were differentially expressed in patients with PTC. A total of 37 key circRNAs were obtained using the SVM-RFE algorithm, whereas 46 key mRNAs were obtained from significant modules in the PPI network. A total of 11 circRNA-miRNA pairs and 40 miRNA-mRNA pairs were predicted. Based on these interaction pairs, 46 circRNA-miRNA-mRNA regulatory pairs were integrated, of which 8 regulatory pairs in line with the ceRNA hypothesis were obtained, including two circRNAs (circ_0004053 and circ_0028198), three miRNAs (miR-199a-5p, miR-199b-5p, and miR-7-5p), and five mRNAs, namely APOA2, CCL20, LPAR5, MFGE8, and TIMP1. Survival analysis showed that LPAR5 expression was associated with patient survival. APOA2 expression showed significant differences between metastatic and non-metastatic tumors, whereas CCL20, LPAR5, MFGE8 and TIMP1 showed significant differences between metastatic and non-metastatic lymph nodes. Overall, we identified several potential targets and regulatory mechanisms involved in PTC. APOA2, CCL20, LPAR5, MFGE8, and TIMP1 may be correlated with PTC metastasis.
format article
author Jie Qiu
Maolin Sun
Chuanshan Zang
Liwei Jiang
Zuorong Qin
Yan Sun
Mingbo Liu
Wenwei Zhang
author_facet Jie Qiu
Maolin Sun
Chuanshan Zang
Liwei Jiang
Zuorong Qin
Yan Sun
Mingbo Liu
Wenwei Zhang
author_sort Jie Qiu
title Five genes involved in circular RNA-associated competitive endogenous RNA network correlates with metastasis in papillary thyroid carcinoma
title_short Five genes involved in circular RNA-associated competitive endogenous RNA network correlates with metastasis in papillary thyroid carcinoma
title_full Five genes involved in circular RNA-associated competitive endogenous RNA network correlates with metastasis in papillary thyroid carcinoma
title_fullStr Five genes involved in circular RNA-associated competitive endogenous RNA network correlates with metastasis in papillary thyroid carcinoma
title_full_unstemmed Five genes involved in circular RNA-associated competitive endogenous RNA network correlates with metastasis in papillary thyroid carcinoma
title_sort five genes involved in circular rna-associated competitive endogenous rna network correlates with metastasis in papillary thyroid carcinoma
publisher AIMS Press
publishDate 2021
url https://doaj.org/article/6d0af47319a84b128b555c3c0ee48d93
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