TY - JOUR
T1 - Analysis of clock gene-miRNA correlation networks reveals candidate drivers in colorectal cancer
AU - Mazzoccoli, Gianluigi
AU - Colangelo, Tommaso
AU - Panza, Anna
AU - Rubino, Rosa
AU - Tiberio, Cristiana
AU - Palumbo, Orazio
AU - Carella, Massimo
AU - Trombetta, Domenico
AU - Gentile, Annamaria
AU - Tavano, Francesca
AU - Valvano, Maria Rosa
AU - Storlazzi, Clelia Tiziana
AU - Macchia, Gemma
AU - De Cata, Angelo
AU - Bisceglia, Giovanni
AU - Capocefalo, Daniele
AU - Colantuoni, Vittorio
AU - Sabatino, Lina
AU - Piepoli, Ada
AU - Mazza, Tommaso
PY - 2016
Y1 - 2016
N2 - Altered functioning of the biological clock is involved in cancer onset and progression. MicroRNAs (miRNAs) interact with the clock genes modulating the function of genetically encoded molecular clockworks. Collaborative interactions may take place within the coding-noncoding RNA regulatory networks. We aimed to evaluate the cross-talk among miRNAs and clock genes in colorectal cancer (CRC). We performed an integrative analysis of miRNA-miRNA and miRNA-mRNA interactions on high-throughput molecular profiling of matched human CRC tissue and non-tumor mucosa, pinpointing core clock genes and their targeting miRNAs. Data obtained in silico were validated in CRC patients and human colon cancer cell lines. In silico we found severe alterations of clock gene-related coding-noncoding RNA regulatory networks in tumor tissues, which were later corroborated by the analysis of human CRC specimens and experiments performed in vitro. In conclusion, specific miRNAs target and regulate the transcription/translation of clock genes and clock gene-related miRNA-miRNA as well as mRNA-miRNA interactions are altered in colorectal cancer. Exploration of the interplay between specific miRNAs and genes, which are critically involved in the functioning of the biological clock, provides a better understanding of the importance of the miRNA-clock genes axis and its derangement in colorectal cancer.
AB - Altered functioning of the biological clock is involved in cancer onset and progression. MicroRNAs (miRNAs) interact with the clock genes modulating the function of genetically encoded molecular clockworks. Collaborative interactions may take place within the coding-noncoding RNA regulatory networks. We aimed to evaluate the cross-talk among miRNAs and clock genes in colorectal cancer (CRC). We performed an integrative analysis of miRNA-miRNA and miRNA-mRNA interactions on high-throughput molecular profiling of matched human CRC tissue and non-tumor mucosa, pinpointing core clock genes and their targeting miRNAs. Data obtained in silico were validated in CRC patients and human colon cancer cell lines. In silico we found severe alterations of clock gene-related coding-noncoding RNA regulatory networks in tumor tissues, which were later corroborated by the analysis of human CRC specimens and experiments performed in vitro. In conclusion, specific miRNAs target and regulate the transcription/translation of clock genes and clock gene-related miRNA-miRNA as well as mRNA-miRNA interactions are altered in colorectal cancer. Exploration of the interplay between specific miRNAs and genes, which are critically involved in the functioning of the biological clock, provides a better understanding of the importance of the miRNA-clock genes axis and its derangement in colorectal cancer.
KW - Circadian
KW - Clock genes
KW - Colorectal cancer
KW - miRNA-mRNA
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UR - http://www.scopus.com/inward/citedby.url?scp=84979901301&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.9989
DO - 10.18632/oncotarget.9989
M3 - Article
AN - SCOPUS:84979901301
VL - 7
SP - 45444
EP - 45461
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 29
ER -