Roles of Circular RNAs And Their Interactions With MicroRNAs in Human Disorders

Zhu

Journal Cellular Physiology

et al. 2019

Circular RNAs have been found to be aberrantly expressed in tumors and their significance in tumorigenesis has been focused on. The role of circDYNC1H1 in hepatocellular carcinoma (HCC) pathogenesis and its relationship with miR‐140‐5p were explored. The expression of circDYNC1H1, miR‐140‐5p, and SULT2B1 in HCC tissues and cells was measured, and Pearson's analysis was used to analyze their expression correlation. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide and Transwell assays were performed to determine cell proliferation and migration. Binding between circDYNC1H1 and miR‐140‐5p was evaluated with RNA pull‐down assay. A luciferase reporter assay was conducted to assess the interaction between circDYNC1H1 and miR‐140‐5p and between miR‐140‐5p and SULT2B1. circDYNC1H1 was highly expressed in HCC tissues (n = 20), and it was negatively associated with the expression of miR‐140‐5p but positively correlated with SULT2B1 messenger RNA expression. circDYNC1H1 was upregulated in cell lines of HCC. Interference of circDYNC1H1 suppressed cell proliferation and migration of HCC. circDYNC1H1 acted as a sponge of miR‐140‐5p. miR‐140‐5p controlled SULT2B1 expression by targeting its 3′‐untranslated region. circDYNC1H1 enhanced SULT2B1 expression via sponging miR‐140‐5p. Downregulation of circDYNC1H1 disturbed cell proliferation and migration of HCC through miR‐140‐5p/SULT2B1 pathway. Silencing of circDYNC1H1 delayed tumor growth in HCC mouse model. Acting like a sponge of miR‐140‐5p, silenced circDYNC1H1 downregulated SULT2B1 to restrain HCC cell proliferation and migration, which is adverse to HCC growth and progression.

mentioning

confidence: 99%

Downregulation of circDYNC1H1 exhibits inhibitor effect on cell proliferation and migration in hepatocellular carcinoma through miR‐140‐5p

Zhu

Journal Cellular Physiology

et al. 2019

“…Non-coding RNAs (ncRNAs) which mainly include circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and microRNAs (miRNAs) exert their regulatory roles in many biological processes, such as tumorigenesis, fibrogenesis, and also, immune regulation 6,7 . LncRNAs are characterized with a length of over 200 nucleotides, and expressed in both cytoplasm and nucleus 8 .…”

Section: Introductionmentioning

confidence: 99%

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

Zhu

et al. 2020

Cell Death Dis

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.

“…In recent years, a strong relationship of circular RNAs (circRNAs) and fibrogenesis has been elucidated. CircRNAs, a novel type of endogenous non-coding RNAs, are characterized by covalently closed loop structures with neither 5’ to 3’ polarity nor a polyadenylated tail [11, 12]. CircRNAs often have a high stability and are less susceptible to degradation as the loop structure is resistant to RNase R and RNA exonuclease [13].…”

Section: Introductionmentioning

confidence: 99%

TGF-β- and lipopolysaccharide-induced upregulation of circular RNA PWWP2A promotes hepatic fibrosis via sponging miR-203 and miR-223

Feng

et al. 2019

Aging

Both transforming growth factor-beta (TGF-β) and lipopolysaccharide (LPS) can activate hepatic stellate cells (HSCs), thus increasing expressions of alpha smooth muscle actin (α-SMA) and type I collagen alpha 1 (Col1α1) and promoting liver fibrosis. However, whether TGF-β and LPS have a common downstream reactor remains unclear. Recently, a strong relationship of circular RNAs (circRNAs) and fibrogenesis has been elucidated. In this study, we compared the expressions of several circRNAs in TGF-β- and LPS-activated HSCs, and found that circ-PWWP2A was upregulated in both TGF-β- and LPS-activated HSCs and in mouse fibrotic liver tissues. Meanwhile, circ-PWWP2A was positively correlated with HSC activation and proliferation. Two microRNAs, miR-203 and miR-223, were identified to be the downstream targets of circ-PWWP2A using luciferase reporter assay and pull-down interaction assay. Circ-PWWP2A was suggested to promote HSC activation and proliferation via sponging miR-203 and miR-223, and subsequently increasing Fstl1 and TLR4, respectively. Furthermore, downregulating circ-PWWP2A was indicated to alleviate hepatic fibrosis in vivo. In conclusion, our findings indicated that circ-PWWP2A is the common downstream reactor of TGF-β and LPS in HSC activation, and that circ-PWWP2A plays a critical role in hepatic fibrogenesis via sponging miR-203 and miR-223.