Circular RNA HIPK3: A Key Circular RNA in a Variety of Human Cancers

Abstract

Circular RNAs (circRNAs), which act as initiators and promoters of various diseases, were thought to be mostly noncoding RNAs (ncRNAs) in eukaryotes, until recent studies confirmed that some circRNAs have the function of encoding proteins. Accumulating research findings have proved that dysregulation of circRNAs is associated with the developmental process of multiple cancers. circHIPK3, an example of circRNA, is frequently expressed in many diseases, such as diabetes, age-related cataract, idiopathic pulmonary fibrosis, preeclampsia, osteoblasts, and retinal vascular dysfunction, leading to disease development and progression. In addition, circHIPK3 may also serve as a potential biomarker, to help us know more about the rules of occurrence and development of cancers. In recent studies, many circHIPK3-related cancers have been identified, including nasopharyngeal carcinoma, gallbladder cancer, lung cancer, hepatocellular carcinoma, osteosarcoma, glioma, colorectal cancer, ovarian cancer, bladder cancer, prostate cancer, gastric cancer, oral squamous cell carcinoma, and chronic myeloid leukemia. This review summarizes recent studies on the biological mechanisms of circHIPK3 and expounds the molecular mechanisms of circHIPK3 in these malignant tumors.

Silencing of circHIPK3 Inhibits Pressure Overload-Induced Cardiac Hypertrophy and Dysfunction by Sponging miR-185-3p

“…13 circHIPK3 is abundant in heart, lungs, liver, etc; its dysregulation is involved in a number of biological processes, including cardiovascular diseases. 14 miRNAs are single stranded, endogenous, small (~22 nucleotides) non-coding RNAs; 15 they are key regulators of post-transcriptional gene expression and their deregulations are associated with several diseases; they are used as potential diagnostic and prognostic biomarkers of cardiovascular diseases. 16 miRNA can target many mRNAs, and a unique mRNA can be the target of multiple miRNAs.…”

“… 13 circHIPK3 is abundant in heart, lungs, liver, etc; its dysregulation is involved in a number of biological processes, including cardiovascular diseases. 14 …”

The Circular RNA-miRNA Axis: A Special RNA Signature Regulatory Transcriptome as a Potential Biomarker for OSCC

“… 58 circHIPK3 is the product of exon 2 of the HIPK3 gene. 59 The role of circHIPK3 was first described in OSCC by Wang et al., 31 where circHIPK3 was upregulated in CAL 27 and SSC15 cell lines when compared with the HOK cell line, and it displayed axis formation with miR-124, resulting in progression of the proliferation of tissue in OSCC. The knockout of circHIPK3 has been shown to reverse these effects, and it upregulated miR-124.…”

Emerging landscape of circHIPK3 and its role in cancer and other diseases (Review)

“…(D) Intron-splicing-driven circularization: Pre-tRNAs are synthesized from introns; excised tRNA introns deriving from pre-tRNAs are removed by tRNA splicing enzymes and ligate the released end to form tRNA and tricRNA. This image was originally published in a study by Wen et al ( 36 ). circRNA, circular RNA; EIciRNA, exon-intron circRNA; ecircRNA, exonic circRNA; tricRNA, tRNA intronic circRNA; ciRNA, circular intronic RNA; RBP, RNA-binding protein.…”

“…The third model is called RBP-binding driven circularization, as RBP has an important function in initiating circRNA formation via regulation of adjacent splice site ( 34 ). Finally, the fourth model is known as intron-splicing-driven circularization; the pre-tRNA is identified and spliced by the tRNA splicing nuclease complex to remove the excised tRNA introns, which then release and ligate the intron termini to form a tRNA and a tricRNA ( 35 , 36 ).…”