CircHIPK2 promotes proliferation of nasopharyngeal carcinoma by down-regulating HIPK2

Transl Cancer Res. 2022 Jul;11(7):2348-2358. doi: 10.21037/tcr-22-1645.

Abstract

Background: Circular RNAs (circRNAs) are a new family of endogenous non-coding RNAs generated by a covalently closed loop, and a mounting body of data suggests they control gene expression. While the circRNA-homeodomain-interacting protein kinase-2 (circHIPK2) is generated from the homeodomain-interacting protein kinase 2 (HIPK2) gene, the function of circHIPK2 in nasopharyngeal cancer (NPC) along with the responsible mechanisms are still unclear.

Methods: RNA-sequencing data was utilized to determine the differentially expressed circRNAs, and circHIPK2 was established as a novel prospective circRNA. The expressions of circRNAs along with messenger RNAs (mRNAs) in NPC tissues and cells was assessed via quantitative real-time polymerase chain reaction (qRT-PCR), and the transfection of NPC cells with plasmids in vitro and in vivo was adopted to explore the effects of circHIPK2 in NPC. Western blotting was adopted to assess the expressions of HIPK2 and β-catenin, while Cell Counting Kit (CCK)-8 assay coupled with colony-forming assay were utilized to assess the biological functions. The expression of nuclear and cytoplasmic HIPK2 was detected via nucleocytoplasmic separation assay.

Results: Herein, we established that circHIPK2 was upregulated in NPC tissues. Over-expression of circHIPK2 promoted cell proliferation in vitro and in vivo, and further studies revealed it inhibited the protein level of HIPK2 in a post-transcriptional pattern, decreasing β-catenin expression and suppressing the proliferation of NPC.

Conclusions: Our findings demonstrated elevated circHIPK2 facilitated the cell proliferation of NPC cells via the circHIPK2/HIPK2 axis, suggesting circHIPK2 might be an oncogene to promote the process of NPC and could be a novel treatment target for its management.

Keywords: circHIPK2; homeodomain-interacting protein kinase 2 (HIPK2); nasopharyngeal carcinoma; proliferation.