The Homeodomain-Interacting Protein Kinases (HIPKs) HIPK1, HIPK2 and HIPK3 are
Ser/Thr kinases which interact with homeobox proteins and other transcription factors, acting as transcriptional
coactivators or corepressors. HIPKs contribute to regulate several biological processes,
such as signal transduction, apoptosis, embryonic development, DNA-damage response, and cellular
proliferation, in response to various extracellular stimuli. Recently it has emerged that, in addition to
their role in cancer, fibrosis and diabetes, HIPKs may also be involved in other human diseases, including
Amyotrophic Lateral Sclerosis (ALS), Rett syndrome, cerebellar diseases, and retinal vascular
Methods: Here, we update our previous paper concerning the regulation of HIPK proteins expression
by microRNAs (miRNAs), pointing out the most recent findings about new cellular mechanisms and
diseases which are affected by the interplay between HIPKs and miRNAs.
Conclusion: Recently, it has emerged that HIPKs and their related miRNAs are involved in diabetic
nephropathy, gastric cancer chemoresistance, cervical cancer progression, and recombinant protein
expression in cultured cells. Interestingly, circular RNAs (circRNAs) deriving from HIPK2 and
HIPK3 loci also modulate cellular proliferation and viability by sponging several miRNAs, thus
emerging as new putative therapeutic targets for diabetes-associated retinal vascular dysfunction,
astrogliosis and cancer.