Discovering miRNA regulatory networks in Holt-Oram Syndrome using a Zebrafish model
microRNAs (miRNAs) are small non-coding RNAs that play an important role in the post- transcriptional regulation of gene expression. miRNAs are involved in the regulation of many biological processes such as differentiation, apoptosis and cell proliferation. miRNAs are expressed in embryonic, postna...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2016-07-01
|
| Series: | Frontiers in Bioengineering and Biotechnology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fbioe.2016.00060/full |
| _version_ | 1828791396769726464 |
|---|---|
| author | Romina D'Aurizio Francesco Russo Francesco Russo Elena Chiavacci Mario Baumgart Marco Groth Mara D'Onofrio Ivan Arisi Giuseppe Rainaldi Letizia Pitto Marco Pellegrini |
| author_facet | Romina D'Aurizio Francesco Russo Francesco Russo Elena Chiavacci Mario Baumgart Marco Groth Mara D'Onofrio Ivan Arisi Giuseppe Rainaldi Letizia Pitto Marco Pellegrini |
| author_sort | Romina D'Aurizio |
| collection | DOAJ |
| description | microRNAs (miRNAs) are small non-coding RNAs that play an important role in the post- transcriptional regulation of gene expression. miRNAs are involved in the regulation of many biological processes such as differentiation, apoptosis and cell proliferation. miRNAs are expressed in embryonic, postnatal, and adult hearts and they have a key role in the regulation of gene expression during cardiovascular development and disease. Aberrant expression of miRNAs is associated with abnormal cardiac cell differentiation and dysfunction. Tbx5 is a member of the T-box gene family which acts as transcription factor involved in the vertebrate heart development. Alteration of Tbx5 level affects the expression of hundreds of genes. Haploinsufficiency and gene duplication of Tbx5 are at the basis of the cardiac abnormalities associated with Holt-Oram syndrome (HOS). Recent data indicate that miRNAs might be an important part of the regulatory circuit through which Tbx5 controls heart development. Using high-throughput technology we characterized genome-widely the miRNA and mRNA expression profiles in WT and Tbx5 depleted zebrafish embryos at two developmental time points, 24 and 48 hours post fertilization (hpf). We found that several miRNAs which are potential effectors of Tbx5 are differentially expressed, some of them are already known to be involved in cardiac development and functions, such as miR-30, miR-34, miR-190, miR-21. We performed an integrated analysis of miRNA expression data with gene expression profiles to refine computational target prediction approaches by means of the inversely correlation of miRNA-mRNA expressions. Interestingly these targets have roles in cardiac contractility, cardiomyocyte proliferation/apoptosis and valve formation which are crucial functions regulated by Tbx5. This approach allowed to discover complex regulatory circuits involving novel miRNAs and protein coding genes not considered before in the HOS such as miR-34a and miR-30 and their targets. |
| first_indexed | 2024-12-12T02:50:06Z |
| format | Article |
| id | doaj.art-b1789fca69e64b4e8281ebe6c6c0b05a |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-12T02:50:06Z |
| publishDate | 2016-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-b1789fca69e64b4e8281ebe6c6c0b05a2022-12-22T00:40:55ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852016-07-01410.3389/fbioe.2016.00060186098Discovering miRNA regulatory networks in Holt-Oram Syndrome using a Zebrafish modelRomina D'Aurizio0Francesco Russo1Francesco Russo2Elena Chiavacci3Mario Baumgart4Marco Groth5Mara D'Onofrio6Ivan Arisi7Giuseppe Rainaldi8Letizia Pitto9Marco Pellegrini10National Research Council (CNR)National Research Council (CNR)University of PisaNational Research Council (CNR)Fritz Lipmann Institute (FLI)Fritz Lipmann Institute (FLI)Fondazione EBRI Rita Levi-MontalciniFondazione EBRI Rita Levi-MontalciniNational Research Council (CNR)National Research Council (CNR)National Research Council (CNR)microRNAs (miRNAs) are small non-coding RNAs that play an important role in the post- transcriptional regulation of gene expression. miRNAs are involved in the regulation of many biological processes such as differentiation, apoptosis and cell proliferation. miRNAs are expressed in embryonic, postnatal, and adult hearts and they have a key role in the regulation of gene expression during cardiovascular development and disease. Aberrant expression of miRNAs is associated with abnormal cardiac cell differentiation and dysfunction. Tbx5 is a member of the T-box gene family which acts as transcription factor involved in the vertebrate heart development. Alteration of Tbx5 level affects the expression of hundreds of genes. Haploinsufficiency and gene duplication of Tbx5 are at the basis of the cardiac abnormalities associated with Holt-Oram syndrome (HOS). Recent data indicate that miRNAs might be an important part of the regulatory circuit through which Tbx5 controls heart development. Using high-throughput technology we characterized genome-widely the miRNA and mRNA expression profiles in WT and Tbx5 depleted zebrafish embryos at two developmental time points, 24 and 48 hours post fertilization (hpf). We found that several miRNAs which are potential effectors of Tbx5 are differentially expressed, some of them are already known to be involved in cardiac development and functions, such as miR-30, miR-34, miR-190, miR-21. We performed an integrated analysis of miRNA expression data with gene expression profiles to refine computational target prediction approaches by means of the inversely correlation of miRNA-mRNA expressions. Interestingly these targets have roles in cardiac contractility, cardiomyocyte proliferation/apoptosis and valve formation which are crucial functions regulated by Tbx5. This approach allowed to discover complex regulatory circuits involving novel miRNAs and protein coding genes not considered before in the HOS such as miR-34a and miR-30 and their targets.http://journal.frontiersin.org/Journal/10.3389/fbioe.2016.00060/fullHeartZebrafishMicroarraymicroRNANGSdata integration |
| spellingShingle | Romina D'Aurizio Francesco Russo Francesco Russo Elena Chiavacci Mario Baumgart Marco Groth Mara D'Onofrio Ivan Arisi Giuseppe Rainaldi Letizia Pitto Marco Pellegrini Discovering miRNA regulatory networks in Holt-Oram Syndrome using a Zebrafish model Frontiers in Bioengineering and Biotechnology Heart Zebrafish Microarray microRNA NGS data integration |
| title | Discovering miRNA regulatory networks in Holt-Oram Syndrome using a Zebrafish model |
| title_full | Discovering miRNA regulatory networks in Holt-Oram Syndrome using a Zebrafish model |
| title_fullStr | Discovering miRNA regulatory networks in Holt-Oram Syndrome using a Zebrafish model |
| title_full_unstemmed | Discovering miRNA regulatory networks in Holt-Oram Syndrome using a Zebrafish model |
| title_short | Discovering miRNA regulatory networks in Holt-Oram Syndrome using a Zebrafish model |
| title_sort | discovering mirna regulatory networks in holt oram syndrome using a zebrafish model |
| topic | Heart Zebrafish Microarray microRNA NGS data integration |
| url | http://journal.frontiersin.org/Journal/10.3389/fbioe.2016.00060/full |
| work_keys_str_mv | AT rominadaurizio discoveringmirnaregulatorynetworksinholtoramsyndromeusingazebrafishmodel AT francescorusso discoveringmirnaregulatorynetworksinholtoramsyndromeusingazebrafishmodel AT francescorusso discoveringmirnaregulatorynetworksinholtoramsyndromeusingazebrafishmodel AT elenachiavacci discoveringmirnaregulatorynetworksinholtoramsyndromeusingazebrafishmodel AT mariobaumgart discoveringmirnaregulatorynetworksinholtoramsyndromeusingazebrafishmodel AT marcogroth discoveringmirnaregulatorynetworksinholtoramsyndromeusingazebrafishmodel AT maradonofrio discoveringmirnaregulatorynetworksinholtoramsyndromeusingazebrafishmodel AT ivanarisi discoveringmirnaregulatorynetworksinholtoramsyndromeusingazebrafishmodel AT giusepperainaldi discoveringmirnaregulatorynetworksinholtoramsyndromeusingazebrafishmodel AT letiziapitto discoveringmirnaregulatorynetworksinholtoramsyndromeusingazebrafishmodel AT marcopellegrini discoveringmirnaregulatorynetworksinholtoramsyndromeusingazebrafishmodel |