CeRNA Expression Profiling Identifies KIT-Related circRNA-miRNA-mRNA Networks in Gastrointestinal Stromal Tumour

Jia, Ning; Tong, Hanxing; Zhang, Yong; Katayama, Hiroshi; Wang, Yuan; Lu, Weiqi; Wang, Jin

doi:10.3389/fgene.2019.00825

Cited by 29 publications

(29 citation statements)

References 44 publications

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“…CircRNAs belong to a family of endogenous ncRNAs without 5′ caps or 3′ tails, which have been implicated in inflammation and immune regulation. Apart from interacting with molecules with biological activity directly, a number of circRNAs have also been confirmed to function as ceRNA in cancer, inflammation-related, or autoimmune diseases 25 – 27 . Although several published studies have identified the specific profile of circRNAs in peripheral blood cells of RA patients, whether those circRNAs can function as ceRNA for the dysregulated miRNAs in RA is not clear yet.…”

Section: Discussionmentioning

confidence: 99%

CircRNA_09505 aggravates inflammation and joint damage in collagen-induced arthritis mice via miR-6089/AKT1/NF-κB axis

et al. 2020

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A number of circular RNAs (circRNAs) have been implicated in rheumatoid arthritis (RA) pathogenesis; however, little is known about their function and hidden molecular mechanism in immune and inflammation regulation. We investigated the role and the underlying mechanism of circRNA_09505 in RA in this study. Real-time PCR and fluorescence in situ hybridization (FISH) are adopted to estimate the quantitative expression and localization of circRNA_09505 in macrophages. The altering effect of circRNA_09505 on inflammation is investigated in vitro and in vivo by use of macrophage cell models and collagen-induced arthritis (CIA) mice. Luciferase reporter assay and RNA-binding protein immunoprecipitation (RIP) are used to confirm the circRNA_09505/miR-6089 ceRNA network predicted by bioinformatics analysis. Compared with controls, the expression of circRNA_09505 is upregulated in peripheral blood mononuclear cells (PBMCs) from patients with RA. The proliferation and cell cycle are significantly promoted when circRNA_09505 is upregulated in macrophages, whereas knockdown of circRNA_09505 inhibits macrophage proliferation and cell- cycle progression. Besides, circRNA_09505 can act as a miRNA sponge for miR-6089 in macrophages, and promote the production of TNF-α, IL-6, and IL-12 through ceRNA mechanism. Moreover, AKT1 is a direct target of miR-6089. CircRNA_09505 can promote AKT1 expression by acting as a miR-6089 sponge via IκBα/NF-κB signaling pathway in macrophages. Most interestingly, knockdown of circRNA_09505 significantly alleviates arthritis and inflammation in vivo in CIA mice. These data support the hypothesis that circRNA_09505 can function as a miR-6089 sponge and regulate inflammation via miR-6089/AKT1/NF-κB axis in CIA mice.

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Section: Discussionmentioning

confidence: 99%

CircRNA_09505 aggravates inflammation and joint damage in collagen-induced arthritis mice via miR-6089/AKT1/NF-κB axis

et al. 2020

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“…Circular RNA circ-CPA4 (hsa_circ_0082374) had recently been identified as an oncogene in glioma [ 34 ], however, little known about the role of this circRNA in regulating progression of other types of cancer. Besides, circRNAs were known as “sponges” for miRNAs, and circRNAs regulated the levels of their downstream miRNAs in a competing endogenous RNA (ceRNA) dependent manner [ 35 – 37 ]. In particular, let-7 miRNA could be sponged and inhibited by circ-CPA4 in the development of glioma [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

Circular RNA circ-CPA4/ let-7 miRNA/PD-L1 axis regulates cell growth, stemness, drug resistance and immune evasion in non-small cell lung cancer (NSCLC)

Hong

Xue

Jiang

et al. 2020

J Exp Clin Cancer Res

259

194

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Background Non-small cell lung cancer (NSCLC) cells derived intracellular and extracellular programmed cell death ligand 1 (PD-L1) promoted cancer progression and drug resistance, and facilitated tumor immune evasion. However, the detailed molecular mechanisms are still largely unknown. In the present study, we aimed to explore the role of circular RNA circ-CPA4/let-7 miRNA/PD-L1 axis in the regulation of NSCLC progression, drug resistance and tumor immune microenvironment. Methods Real-Time qPCR and Western Blot analysis were conducted to examine gene expressions at transcriptional and translated levels, respectively. The regulatory mechanisms of circ-CPA4, let-7 miRNA and PD-L1 were validated by dual-luciferase reporter gene system and RNA pull-down assay. Cell growth and apoptosis were determined by CCK-8 assay, colony formation assay and Annexin V-FITC/PI double staining assay. Cell mobility was evaluated by transwell assay. Results Circ-CPA4 and PD-L1 were high-expressed, while let-7 miRNA was low-expressed in NSCLC cells and cancer tissues compared to the human bronchial epithelial (HBE) cells and their paired clinical normal adjacent tissues, respectively. Besides, knock-down of circ-CPA4 inhibited cell growth, mobility and epithelial-mesenchymal transition (EMT), and promoted cell death in NSCLC cells by downregulating PD-L1 through serving as a RNA sponge for let-7 miRNA. In addition, the NSCLC cells derived PD-L1-containing exosomes promoted cell stemness and increased resistance of NSCLC cells to cisplatin. Notably, by co-culturing the NSCLC cells with CD8 + T cells isolated from human peripheral blood mononuclear cells (hPBMCs) in a transwell co-culturing system, we found that NSCLC cells inactivated CD8 + T cells in a secreted PD-L1-dependent manner. Further results suggested that circ-CPA4 also positively regulated exosomal PD-L1, and the NSCLC cells with circ-CPA4 ablation re-activated CD8 + T cells in the co-culturing system. Conclusion Taken together, circ-CPA4 regulated cell growth, mobility, stemness and drug resistance in NSCLC cells and inactivated CD8 + T cells in the tumor immune microenvironment through let-7 miRNA/PD-L1 axis.

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“…CircRNA-miRNA-mRNA network is a widely recognized mode of action in cancer progression [31]. We deduced that circ_0086720 also functioned as a competing endogenous RNA (ceRNA) by targeting downstream miRNAs.…”

Section: Discussionmentioning

confidence: 99%

Circ_0086720 knockdown strengthens the radiosensitivity of non-small cell lung cancer via mediating the miR-375/SPIN1 axis

Jin

Sheng

et al. 2021

neo

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Radioresistance is an important cause of cancer treatment failure. Circular RNAs (circRNAs) play crucial roles in cancer development, including the radioresistance. This research aimed to determine the function and related mechanism of circ_0086720 in the radioresistance of non-small cell lung cancer (NSCLC). The expression of circ_0086720, miR-375, and Spindlin 1 (SPIN1) was measured using a quantitative real-time polymerase chain reaction (qRT-PCR). Cell survival fraction was analyzed using colony formation assay, and cell apoptosis was monitored b y flow cytometry assay. The activities of caspase3 and caspase9 were assessed using the corresponding commercial kits. The ed by western blot. Bioinformatics analysis was performed to predict the targets of circ_0086720 and miR-375. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA pull-down assay were conducted to validate the interaction between miR-375 and circ_0086720 or SPIN1. The animal model was constructed to ascertain the role of circ_0086720 in vivo. The expression of circ_0086720 and SPIN1 was increased in the radioresistant NSCLC tissues, while miR-375 expression was decreased. The circ_0086720 knockdown sensitized NSCLC cells to the radiation to further inhibit cell survival and induce cell apoptosis. Circ_0086720 targeted miR-375 and suppressed miR-375 expression, and miR-375 bound to SPIN1 to impair SPIN1 expression. miR-375 deficiency or SPIN1 overexpression could attenuate circ_0086720 knockdown-mediated radiosensitivity. The circ_0086720 knockdown also enhanced radiosensitivity to further block tumor growth in vivo. To conclude, circ_0086720 downregulation enhanced the sensitivity of NSCLC to radiation by regulating the miR-375/SPIN1 axis, contributing to the improvement of the radiotherapies in NSCLC.

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CeRNA Expression Profiling Identifies KIT-Related circRNA-miRNA-mRNA Networks in Gastrointestinal Stromal Tumour

Cited by 29 publications

References 44 publications

CircRNA_09505 aggravates inflammation and joint damage in collagen-induced arthritis mice via miR-6089/AKT1/NF-κB axis

CircRNA_09505 aggravates inflammation and joint damage in collagen-induced arthritis mice via miR-6089/AKT1/NF-κB axis

Circular RNA circ-CPA4/ let-7 miRNA/PD-L1 axis regulates cell growth, stemness, drug resistance and immune evasion in non-small cell lung cancer (NSCLC)

Circ_0086720 knockdown strengthens the radiosensitivity of non-small cell lung cancer via mediating the miR-375/SPIN1 axis

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