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Bioinformatic Analysis of miR-200b/429 and Hub Gene Network in Cervical Cancer

The miR-200b/429 located at 1p36 is a highly conserved miRNA cluster emerging as a critical regulator of cervical cancer. Using publicly available miRNA expression data from TCGA and GEO followed by independent validation, we aimed to identify the association between miR-200b/429 expression and cerv...

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Autores principales: Shukla, Vaibhav, Mallya, Sandeep, Adiga, Divya, Sriharikrishnaa, S., Chakrabarty, Sanjiban, Kabekkodu, Shama Prasada
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10517900/
https://www.ncbi.nlm.nih.gov/pubmed/36879084
http://dx.doi.org/10.1007/s10528-023-10356-2
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author Shukla, Vaibhav
Mallya, Sandeep
Adiga, Divya
Sriharikrishnaa, S.
Chakrabarty, Sanjiban
Kabekkodu, Shama Prasada
author_facet Shukla, Vaibhav
Mallya, Sandeep
Adiga, Divya
Sriharikrishnaa, S.
Chakrabarty, Sanjiban
Kabekkodu, Shama Prasada
author_sort Shukla, Vaibhav
collection PubMed
description The miR-200b/429 located at 1p36 is a highly conserved miRNA cluster emerging as a critical regulator of cervical cancer. Using publicly available miRNA expression data from TCGA and GEO followed by independent validation, we aimed to identify the association between miR-200b/429 expression and cervical cancer. miR-200b/429 cluster was significantly overexpressed in cancer samples compared to normal samples. miR-200b/429 expression did not correlate with patient survival; however, its overexpression correlated with histological type. Protein–protein interaction analysis of 90 target genes of miR-200b/429 identified EZH2, FLT1, IGF2, IRS1, JUN, KDR, SOX2, MYB, ZEB1, and TIMP2 as the top ten hub genes. PI3K–AKT and MAPK signaling pathways emerged as major target pathways of miR-200b/429 and their hub genes. Kaplan–Meier survival analysis showed the expression of seven miR-200b/429 target genes (EZH2, FLT1, IGF2, IRS1, JUN, SOX2, and TIMP2) to influence the overall survival of patients. The miR-200a-3p and miR-200b-5p could help predict cervical cancer with metastatic potential. The cancer hallmark enrichment analysis showed hub genes to promote growth, sustained proliferation, resistance to apoptosis, induction of angiogenesis, activation of invasion, and metastasis, enabling replicative immortality, evading immune destruction, and tumor-promoting inflammation. The drug–gene interaction analysis identified 182 potential drugs to interact with 27 target genes of miR-200b/429 with paclitaxel, doxorubicin, dabrafenib, bortezomib, docetaxel, ABT-199, eribulin, vorinostat, etoposide, and mitoxantrone emerging as the top ten best candidate drugs. Taken together, miR-200b/429 and associated hub genes can be helpful for prognostic application and clinical management of cervical cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10528-023-10356-2.
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spelling pubmed-105179002023-09-25 Bioinformatic Analysis of miR-200b/429 and Hub Gene Network in Cervical Cancer Shukla, Vaibhav Mallya, Sandeep Adiga, Divya Sriharikrishnaa, S. Chakrabarty, Sanjiban Kabekkodu, Shama Prasada Biochem Genet Original Article The miR-200b/429 located at 1p36 is a highly conserved miRNA cluster emerging as a critical regulator of cervical cancer. Using publicly available miRNA expression data from TCGA and GEO followed by independent validation, we aimed to identify the association between miR-200b/429 expression and cervical cancer. miR-200b/429 cluster was significantly overexpressed in cancer samples compared to normal samples. miR-200b/429 expression did not correlate with patient survival; however, its overexpression correlated with histological type. Protein–protein interaction analysis of 90 target genes of miR-200b/429 identified EZH2, FLT1, IGF2, IRS1, JUN, KDR, SOX2, MYB, ZEB1, and TIMP2 as the top ten hub genes. PI3K–AKT and MAPK signaling pathways emerged as major target pathways of miR-200b/429 and their hub genes. Kaplan–Meier survival analysis showed the expression of seven miR-200b/429 target genes (EZH2, FLT1, IGF2, IRS1, JUN, SOX2, and TIMP2) to influence the overall survival of patients. The miR-200a-3p and miR-200b-5p could help predict cervical cancer with metastatic potential. The cancer hallmark enrichment analysis showed hub genes to promote growth, sustained proliferation, resistance to apoptosis, induction of angiogenesis, activation of invasion, and metastasis, enabling replicative immortality, evading immune destruction, and tumor-promoting inflammation. The drug–gene interaction analysis identified 182 potential drugs to interact with 27 target genes of miR-200b/429 with paclitaxel, doxorubicin, dabrafenib, bortezomib, docetaxel, ABT-199, eribulin, vorinostat, etoposide, and mitoxantrone emerging as the top ten best candidate drugs. Taken together, miR-200b/429 and associated hub genes can be helpful for prognostic application and clinical management of cervical cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10528-023-10356-2. Springer US 2023-03-07 2023 /pmc/articles/PMC10517900/ /pubmed/36879084 http://dx.doi.org/10.1007/s10528-023-10356-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Shukla, Vaibhav
Mallya, Sandeep
Adiga, Divya
Sriharikrishnaa, S.
Chakrabarty, Sanjiban
Kabekkodu, Shama Prasada
Bioinformatic Analysis of miR-200b/429 and Hub Gene Network in Cervical Cancer
title Bioinformatic Analysis of miR-200b/429 and Hub Gene Network in Cervical Cancer
title_full Bioinformatic Analysis of miR-200b/429 and Hub Gene Network in Cervical Cancer
title_fullStr Bioinformatic Analysis of miR-200b/429 and Hub Gene Network in Cervical Cancer
title_full_unstemmed Bioinformatic Analysis of miR-200b/429 and Hub Gene Network in Cervical Cancer
title_short Bioinformatic Analysis of miR-200b/429 and Hub Gene Network in Cervical Cancer
title_sort bioinformatic analysis of mir-200b/429 and hub gene network in cervical cancer
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10517900/
https://www.ncbi.nlm.nih.gov/pubmed/36879084
http://dx.doi.org/10.1007/s10528-023-10356-2
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