Nemzeti Kardiovaszkuláris Laboratórium(RRF-2.3.1-21-2022-00003) Támogató: NKFIH
Through binding to complementary mRNAs, microRNAs (miRNAs) mediate gene silencing.
The stability and half-life of microRNAs are controlled by two isoforms of the RNA-binding
protein Roquin. This study aimed at identifying the role of Roquin to miRNA-dependent
regulation of the transcriptome in the post-ischemic heart. Both Roquin isoforms are
highly conserved between rats and humans and constitutively expressed in cardiomyocytes.
In both cell species, hypoxia induces a down-regulation of Roquin-1 and Roquin-2.
An integrative miRNA-and-mRNA analysis (MMIA) identified miR-23b-5p as a potential
interaction partner of Roquins. The open data bank TargetScan8.0 suggests that the
transcription factor ZBTB20 is a potential target of miR-23b-5p. The level of expression
of ZBTB20 correlated with the functional recovery of rat hearts after myocardial infarction.
Moreover, the down-regulation of Roquin-2 in AC16 cells by siRNA under normoxic conditions
was associated with an up-regulation of miR-23b-5p and a down-regulation of ZBTB20.
Furthermore, in the case of hypoxia-dependent down-regulation of Roquin, the subsequent
down-regulation of ZBTB20 was reversed with the help of an antagomir against miR-23b-5p.
In conclusion, hypoxia-induced down-regulation of the two Roquin isoforms was associated
with an increased stability of miR-23b-5p, a Roquin-2-dependent miRNA, which subsequently
led to silencing of the transcription factor ZBTB20.
