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Open AccessArticle

Integrated Analysis of miRNA and mRNA Endorses a Twenty miRNAs Signature for Colorectal Carcinoma

1
Istituto di Ricerca Genetica e Biomedica (IRGB), CNR, Cittadella Universitaria di Cagliari, 09042 Monserrato (CA), Italy
2
CRS4, Science and Technology Park Polaris, Piscina Manna, 09050 Pula (CA), Italy
3
Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43-b, 07100 Sassari, Italy
4
Department of Medical, Surgical and Experimental Sciences, University of Sassari, Viale San Pietro 8, 07100 Sassari, Italy
5
Department of Prevention, Registro Tumori Provincia di Sassari, ASSL Sassari-ATS Sardegna, Via Rizzeddu 21, 07100 Sassari, Italy
6
Department of Pathology, AOU Sassari, Via Matteotti 60, 07100 Sassari, Italy
7
Department of Diagnostic Services, “Giovanni Paolo II” Hospital, ASSL Olbia-ATS Sardegna, Via Bazzoni-Sircana, 07026 Olbia, Italy
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(16), 4067; https://doi.org/10.3390/ijms20164067
Received: 29 July 2019 / Revised: 16 August 2019 / Accepted: 17 August 2019 / Published: 20 August 2019
Colorectal cancer (CRC) ranks as the most frequent carcinoma worldwide. CRC patients show strong prognostic differences and responses to treatment, and 20% have incurable metastatic disease at diagnosis. We considered it essential to investigate mechanisms that control cellular regulatory networks, such as the miRNA–mRNA interaction, known to be involved in cancer pathogenesis. We conducted a human miRNome analysis by TaqMan low density array, comparing CRC to normal colon tissue (NCT, and experimentally identified gene targets of miRNAs deregulated, by anti-correlation analysis, with the CRC whole-transcriptome profile obtained from RNASeq experiments. We identified an integrated signature of 20 deregulated miRNAs in CRC. Enrichment analyses of the gene targets controlled by these miRNAs brought to light 25 genes, members of pathways known to lead to cell growth and death (CCND1, NKD1, FZD3, MAD2L1, etc.), such as cell metabolism (ACSL6, PRPS1-2). A screening of prognosis-mediated miRNAs underlined that the overexpression of miR-224 promotes CRC metastasis, and is associated with high stage and poor survival. These findings suggest that the biology and progression of CRC depend on deregulation of multiple miRNAs that cause a complex dysfunction of cellular molecular networks. Our results have further established miRNA–mRNA interactions and defined multiple pathways involved in CRC pathogenesis. View Full-Text
Keywords: Colorectal cancer; miRNA-mRNA interactions; MicroRNA expression profile; ACSL6; PRPS1; PRPS2; WNT signaling pathway; Hippo signaling pathway; Apelin signaling pathway; Ferroptosis Colorectal cancer; miRNA-mRNA interactions; MicroRNA expression profile; ACSL6; PRPS1; PRPS2; WNT signaling pathway; Hippo signaling pathway; Apelin signaling pathway; Ferroptosis
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Angius, A.; Uva, P.; Pira, G.; Muroni, M.R.; Sotgiu, G.; Saderi, L.; Uleri, E.; Caocci, M.; Ibba, G.; Cesaraccio, M.R.; Serra, C.; Carru, C.; Manca, A.; Sanges, F.; Porcu, A.; Dolei, A.; Scanu, A.M.; Cossu Rocca, P.; De Miglio, M.R. Integrated Analysis of miRNA and mRNA Endorses a Twenty miRNAs Signature for Colorectal Carcinoma. Int. J. Mol. Sci. 2019, 20, 4067.

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