The regulatory network among CircHIPK3, LncGAS5, and miR-495 promotes Th2 differentiation in allergic rhinitis

Abstract

Allergic rhinitis (AR) is a common allergic disease which is characterized by the promotion of Th2 differentiation of CD4 + T cells. However, the mechanisms underlying Th2 differentiation remain unclear. Non-coding RNAs play a critical role in Th2 differentiation, whereas few studies have revealed the interactions among long non-coding RNAs, circular RNAs, and microRNAs. In this study, the differential expressions of several circRNAs and lncRNAs were compared in nasal mucosa samples of AR patients and mice with experimentally induced AR as compared to healthy controls. The results showed that the highly expressed CircHIPK3 and LncGAS5 promoted Th2 differentiation of ovalbumin-induced CD4 + T cells and aggravated nasal symptoms of AR mice. We also found that CircHIPK3 and LncGAS5 induced the upregulation of Th2 cell-specific transcript factor GATA-3 via modulating their common target miR-495. Meanwhile, the intranasal administration of CircHIPK3 or LncGAS5 knockdown lentivirus decreased nasal symptoms of AR mice. In conclusion, our findings indicated that the interactions among CircHIPK3, LncGAS5, and miR-495 play a critical role in the regulation of Th2 differentiation in AR.

circHIPK3 regulates proliferation and differentiation of myoblast through the miR‐7/TCF12 pathway

“…circHIPK3, which originates from exon 2 of the HIPK3 gene, is also known as bladder cancer‐related circular RNA‐2 (Salzman et al, 2013; Zheng et al, 2016). Previous studies have shown that circHIPK3 is stably expressed in different cell lines and tissues (Jeck & Sharpless, 2014; Starke et al, 2015) and promotes the proliferation and differentiation of human colon cancer HCT116 cells, human liver cancer HuH7 cells, human cervical cancer HeLa cells, and helper T cells by sponging multiple miRNAs (Zheng et al, 2016; Zhu et al, 2020). In addition, some studies reported that circHIPK3 plays a role in promoting myoblast proliferation and differentiation by sponging miR‐30a‐3p (Chen et al, 2019), miR‐124, and miR‐379 (Yao et al, 2020).…”

Biogenesis, cellular effects, and biomarker value of circHIPK3

“…CircHIPK3 could induce the upregulation of Th2 cell-specific transcription factor GATA-3 by regulating its target miR-495, thereby promoting ovalbumin-induced Th2 differentiation, which lead to aggravated nasal symptoms in asthmatic model (AS) mice. They also found that nasal symptoms in AR mice could be relieved by intranasal administration of circHIPK3 [ 104 ].…”

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

“…AR is the most common allergic disease affecting individuals of various demographics worldwide ( 103 ). circHIPK3 and long non-coding RNA (lncGAS5) were shown to promote differentiation of T helper 2 cells and aggravate AR via modulating their common target miR-495 ( 104 ). Moreover, intranasal administration of circHIPK3/lncGAS5 knockdown lentivirus resulted in a decrease in AR symptoms by downregulating GATA binding protein 3 expression, highlighting a potential therapeutic means for AR management ( 104 ).…”