OAS1, OAS2, and OAS3 Contribute to Epidermal Keratinocyte Proliferation by Regulating Cell Cycle and Augmenting IFN-1‒Induced Jak1‒Signal Transducer and Activator of Transcription 1 Phosphorylation in Psoriasis

Huang, Yan-Zhou; Zheng, Yuzhen; Zhou, Yuan; Xu, Fangying; Cui, Ying-Zhe; Chen, Xueyan; Wang, Zhao-Yuan; Yan, Binjun; Zheng, Min; Man, Xiao‐Yong

doi:10.1016/j.jid.2022.02.018

Cited by 30 publications

(18 citation statements)

References 28 publications

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“…Additionally, keratinocytes are involved in antigen presentation and innate immune response [ 25 ]. Consistent with this, our results indicated that the activation of innate immunity in keratinocytes plays an important role in psoriatic inflammation.…”

Section: Discussionmentioning

confidence: 99%

LncRNA UCA1 promotes keratinocyte-driven inflammation via suppressing METTL14 and activating the HIF-1α/NF-κB axis in psoriasis

Jiang

et al. 2023

Cell Death Dis

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Keratinocytes are closely associated with innate immunity and inflammatory responses, and are dysregulated during the development of psoriasis, but the underlying mechanisms are not yet fully understood. This work aims to reveal the effects of long non-coding RNA (lncRNA) UCA1 in psoriatic keratinocytes. UCA1 was identified as a psoriasis-related lncRNA that highly expressed in psoriatic lesions. The transcriptome and proteome data of keratinocyte cell line HaCaT showed that UCA1 could positively regulate inflammatory functions, such as response to cytokine. Furthermore, UCA1 silencing decreased inflammatory cytokine secretion and innate immunity gene expression in HaCaT, its culture supernatant also decreased the migration and tube formation ability of vascular endothelial cells (HUVECs). Mechanistically, UCA1 activated the NF-κB signaling pathway, which is regulated by HIF-1α and STAT3. We also observed a direct interaction between UCA1 and N6-methyladenosine (m6A) methyltransferase METTL14. Knocking down METTL14 counteracted the effects of UCA1 silencing, indicating that it can suppress inflammation. In addition, the levels of m6A-modified HIF-1α were decreased in psoriatic lesions, indicating that HIF-1α is a potential target of METTL14. Taken together, this work indicates that UCA1 positively regulates keratinocyte-driven inflammation and psoriasis development by binding to METTL14, and activating HIF-1α and NF-κB signaling pathway. Our findings provide new insights into the molecular mechanisms of keratinocyte-driven inflammation in psoriasis.

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Section: Discussionmentioning

confidence: 99%

LncRNA UCA1 promotes keratinocyte-driven inflammation via suppressing METTL14 and activating the HIF-1α/NF-κB axis in psoriasis

Jiang

et al. 2023

Cell Death Dis

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“…16,23,24 Lu L et al found that OAS1 knockdown inhibited the malignant behavior of pancreatic ductal adenocarcinoma (PDAC) cells. 25 OASL as a member of OAS family is initially identified to involve in cellular innate immunity and exerts antiviral activity against many viruses. [26][27][28][29] However, recent studies demonstrate that OASL participates in the occurrence and progression of tumors.…”

Section: Discussionmentioning

confidence: 99%

“…The OAS family is abnormally expressed in cancer and is closely related to prognosis 16,23,24 . Lu L et al found that OAS1 knockdown inhibited the malignant behavior of pancreatic ductal adenocarcinoma (PDAC) cells 25 . OASL as a member of OAS family is initially identified to involve in cellular innate immunity and exerts antiviral activity against many viruses 26–29 .…”

Section: Discussionmentioning

confidence: 99%

OASL knockdown inhibits the progression of stomach adenocarcinoma by regulating the mTORC1 signaling pathway

et al. 2023

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The present study investigated the effects of 2′‐5′ oligoadenylate synthetase‐like (OASL) on the biological functions of stomach adenocarcinoma (STAD) cells and tumor formation in nude mice. The differential expression levels of OASL in the different cancer types from TCGA dataset were analyzed using gene expression profiling interactive analysis. Overall survival and the receiver operating characteristic were analyzed using the KM plotter and R, respectively. Furthermore, OASL expression and its effects on the biological functions of STAD cells were detected. The possible upstream transcription factors of OASL were predicted using JASPAR. The downstream signaling pathways of OASL were analyzed using GSEA. Tumor formation experiments were performed to evaluate the effect of OASL on tumor formation in nude mice. The results showed that OASL was highly expressed in STAD tissues and cell lines. OASL knockdown markedly inhibited cell viability, proliferation, migration, and invasion and accelerated STAD cell apoptosis. Conversely, OASL overexpression had the opposite effect on STAD cells. JASPAR analysis revealed that STAT1 is an upstream transcription factor of OASL. Furthermore, GSEA showed that OASL activated the mTORC1 signaling pathway in STAD. The protein expression levels of p‐mTOR and p‐RPS6KB1 were suppressed by OASL knockdown and promoted by OASL overexpression. The mTOR inhibitor, rapamycin, markedly reversed the effect of OASL overexpression on STAD cells. Additionally, OASL promoted tumor formation and increased tumor weight and volume in vivo. In conclusion, OASL knockdown suppressed the proliferation, migration, invasion, and tumor formation of STAD cells by inhibiting the mTOR signaling pathway.

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“…When we manipulated the levels of UCA1, the expression of innate immunity-related genes changed accordingly, and their relationship was stable across experiments, GEO datasets, HaCaT transcriptome data, and proteomic data. Keratinocytes are reported to have an antigen-presenting function and are involved in innate immune defense response 24 . According to this evidence, the activation of innate immunity may be a more crucial initiating factor of in ammation response in psoriatic keratinocytes.…”

Section: Discussionmentioning

confidence: 99%

LncRNA UCA1 promotes keratinocyte inflammation via suppressing METTL14 and activating the HIF-1α/NF-κB axis in psoriasis

Jiang

et al. 2023

Preprint

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Psoriatic inflammation can be regulated by epigenetic factors, but little is known about their role. This work aims to reveal the effects of lncRNA UCA1 in keratinocyte inflammation. UCA1 was a psoriasis-related lncRNA in eight GEO transcriptome datasets and psoriatic skin. When we over-expressed or knocked down UCA1 in the keratinocyte cell line (HaCaT), the transcriptome and proteomic data showed that UCA1 could positively regulate inflammatory functions, such as response to cytokine. Experimental findings confirmed that UCA1 could increase inflammatory cytokine secretion, innate immunity gene expression, and ability of vascular endothelial cells. Besides, UCA1 could activate the NF-κB signaling pathway, which might be the target of UCA1-incuded HIF-1α and STAT3. We then uncovered the direct interactions between UCA1 and N6-methyladenosine (m6A) methyltransferase METTL14. METTL14 proved to be a functional suppressor of inflammation, it could antagonize the functions of UCA1. Subsequently, we found the m6A levels of HIF-1α were decreased in psoriatic lesions, thus HIF-1α could be the target of METTL14. In general, this work indicates that UCA1 can positively regulate keratinocytes inflammation and psoriasis development, it binds METTL14 and then activates HIF-1α and NF-κB signaling pathway. Our work presents a new understanding of UCA1 and METTL14 in psoriatic inflammation.

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OAS1, OAS2, and OAS3 Contribute to Epidermal Keratinocyte Proliferation by Regulating Cell Cycle and Augmenting IFN-1‒Induced Jak1‒Signal Transducer and Activator of Transcription 1 Phosphorylation in Psoriasis

Cited by 30 publications

References 28 publications

LncRNA UCA1 promotes keratinocyte-driven inflammation via suppressing METTL14 and activating the HIF-1α/NF-κB axis in psoriasis

LncRNA UCA1 promotes keratinocyte-driven inflammation via suppressing METTL14 and activating the HIF-1α/NF-κB axis in psoriasis

OASL knockdown inhibits the progression of stomach adenocarcinoma by regulating the mTORC1 signaling pathway

LncRNA UCA1 promotes keratinocyte inflammation via suppressing METTL14 and activating the HIF-1α/NF-κB axis in psoriasis

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