Conte Andrea, Pierantoni Giovanna Maria
Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", via 80131, Naples, Italy.
Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD, United States.
Microrna. 2018;7(3):178-186. doi: 10.2174/2211536607666180525102330.
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 dysfunction.
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.
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.
同源结构域相互作用蛋白激酶（HIPKs）中的HIPK1、HIPK2和HIPK3是丝氨酸/苏氨酸激酶，它们与同源框蛋白及其他转录因子相互作用，充当转录共激活因子或共抑制因子。HIPKs有助于调节多种生物学过程，如信号转导、细胞凋亡、胚胎发育、DNA损伤反应和细胞增殖，以响应各种细胞外刺激。最近发现，除了在癌症、纤维化和糖尿病中的作用外，HIPKs还可能参与其他人类疾病，包括肌萎缩侧索硬化症（ALS）、雷特综合征、小脑疾病和视网膜血管功能障碍。
在此，我们更新了之前关于微小RNA（miRNA）对HIPK蛋白表达调控的论文，指出了关于受HIPKs与miRNAs相互作用影响的新细胞机制和疾病的最新发现。
最近发现，HIPKs及其相关miRNAs参与了糖尿病肾病、胃癌化疗耐药、宫颈癌进展以及培养细胞中的重组蛋白表达。有趣的是，源自HIPK2和HIPK3基因座的环状RNA（circRNAs）也通过吸附多种miRNAs来调节细胞增殖和活力，从而成为糖尿病相关视网膜血管功能障碍、星形胶质细胞增生和癌症新的潜在治疗靶点。
