Circ-HSP90A expedites cell growth, stemness, and immune evasion in non-small cell lung cancer by regulating STAT3 signaling and PD-1/PD-L1 checkpoint

Lei, Jie; Zhu, Jianfei; Hui, Bengang; Jia, Chenghui; Yan, Xiaolong; Jiang, Tao; Wang, Xiaoping

doi:10.1007/s00262-022-03235-z

Cited by 17 publications

(19 citation statements)

References 40 publications

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“…Recent evidence has shown the extensive functional effects of circRNAs in lung cancer. Lei et al found that circ-HSP90A is upregulated in lung cancer and plays a pivotal role in cancer cell growth, stemness, and immune evasion [14]. Sun et al highlighted poor circ_0006427 expression in lung cancer and concluded that ectopic circ_0006427 expression impairs the multiplicative, migratory, and invasive abilities of cancer cells [15].…”

Section: Discussionmentioning

confidence: 99%

Hsa_circ_0080608 Attenuates Lung Cancer Progression by Functioning as a Competitive Endogenous RNA to Regulate the miR-661/ADRA1A Pathway

Ren,

Cui,

et al. 2023

Horm Metab Res

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Circular RNAs (circRNAs) participate in the progression of human cancers and have been broadly elucidated. Here, we aimed to elucidate the roles and functional mechanisms of hsa_circ_0080608 (circ_0080608) in lung cancer. Quantitative real-time PCR (qPCR) was performed to assess the mRNA expression levels of circ_0080608, miR-661, and adrenoceptor alpha 1A (ADRA1A). Western blotting was performed to measure ADRA1A protein levels. CCK-8, colony formation, and Transwell assays were performed to determine the effect of circ_0080608 on cell proliferation and migration. Animal models were used to assess how circ_0080608 influences tumor progression in vivo. The binding relationships of miR-661’s with circ_0080608 and ADRA1A was confirmed using dual-luciferase reporter and RIP assays. Circ_0080608 exhibited relatively low expression in lung cancer samples and cells. Lung cancer cells overexpressing circ_0080608 exhibited reduced migratory and proliferative abilities. Additionally, circ_0080608 binds to miR-661 and operates as a competing endogenous RNA (ceRNA) and shares a miR-661 binding site with the 3’ UTR of ADRA1A. Furthermore, circ_0080608 inversely regulates miR-661 expression, consequently restraining the aggressive behavior of lung cancer cells. Lung cancer cells overexpressing ADRA1A also exhibit repressed migratory and proliferative abilities. However, reintroduction of miR-661 led to a decline in ADRA1A expression, thereby attenuating the functional effects of ADRA1A. Circ_0080608 impedes lung cancer progression by regulating the miR-661/ADRA1A pathway. Our findings provide new insights into the progression of lung cancer.

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Section: Discussionmentioning

confidence: 99%

Hsa_circ_0080608 Attenuates Lung Cancer Progression by Functioning as a Competitive Endogenous RNA to Regulate the miR-661/ADRA1A Pathway

Ren,

Cui,

et al. 2023

Horm Metab Res

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“…The circ‐CPA4, circ‐HSP90A, and circFOXK2 were upregulated in non‐small cell lung cancer (NSCLC) (Hong et al, 2020; J. Lei et al, 2022; N. Zhang, Fan, & Deng, 2022). The circ‐CPA4 elevated PD‐L1 expression by sponging let‐7, which enabled NSCLC cells to inactivate CD8 + T cells (Hong et al, 2020).…”

Section: Cancer‐derived Ncrnas and Immune Checkpoint Ligandsmentioning

confidence: 99%

“…The circ‐CPA4 elevated PD‐L1 expression by sponging let‐7, which enabled NSCLC cells to inactivate CD8 + T cells (Hong et al, 2020). The circ‐HSP90A absorbed miR‐424‐5p to increase PD‐L1 expression, thereby inducing the apoptosis of CD8 + T cells (J. Lei et al, 2022). The circFOXK2 served as a sponge for miR‐485‐5p to upregulate PD‐L1 expression and then inhibited the cytotoxicity of CD8 + T cells against NSCLC cells (N. Zhang, Fan, & Deng, 2022).…”

Section: Cancer‐derived Ncrnas and Immune Checkpoint Ligandsmentioning

confidence: 99%

Cancer‐derived non‐coding RNAs endow tumor microenvironment with immunosuppressive properties

Hu,

Shi,

et al. 2023

WIREs RNA

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Non‐coding RNAs (ncRNAs) have attracted extensive attention due to their vital roles in tumorigenesis and progression, especially in the immunotherapy resistance. Tumor immunotherapy resistance is a crucial factor hindering the efficacy of tumor treatments, which can be largely attributed to the immunosuppressive properties of tumor microenvironment. Current studies have revealed that cancer‐derived ncRNAs are involved in the formation of tumor immunosuppressive microenvironment (TIME) through multiple ways. They not only promote the expression of immune checkpoint ligands (e.g., PD‐L1, CD47, Gal‐9, and CD276) on cancer cell surfaces, but also enhance the secretion of immunosuppressive cytokines (e.g., TGF‐β, IL‐6, IL‐10, VEGF, and chemokines). Cancer‐derived ncRNAs could also be transferred into surrounding immune‐related cells through extracellular vesicles, thereby inhibiting the cytotoxicity of CD8+T cells and NK cells, restraining the DC‐mediated antigen presentation, inducing the immunosuppressive phenotype transformation of TAMs and CAFs, and enhancing the immunosuppressive functions of Tregs and MDSCs. Herein, we summarize the roles of cancer‐derived ncRNAs in regulating TIME formation and further explore their potential applications as prognostic biomarkers and immunotherapeutic targets, which will help us to address the TIME‐mediated immunotherapy resistance in the future.This article is categorized under: RNA in Disease and Development > RNA in Disease Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs

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“…Nowadays, circRNA has been widely used in many fields. Studies have shown that circ-HSP90A promotes cell growth and immune escape in non-small cell lung cancer by regulating STAT3 signal transduction and programmed cell death 1 (PD-1)/PD-L1 checkpoint [ 15 ]. Accumulating evidence shows that circRNA is related to the origin and development of cutaneous malignant melanoma, and can be used as a biomarker for early diagnosis of melanoma [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Circ_0011129 Encapsulated by the Small Extracellular Vesicles Derived from Human Stem Cells Ameliorate Skin Photoaging

Zhang

Yao

et al. 2022

IJMS

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Photoaging is not only the main cause of skin aging caused by exogenous factors, it is also related to a variety of skin diseases and even malignant tumors. Excessive and repeated exposure to ultraviolet radiation, especially UVA induces oxidative stress, DNA damage, inflammation, and collagen and elastin degeneration, ultimately leads to skin photoaging, manifested by skin redness, coarse wrinkles, and pigmentation even skin cancer. There has been a large demand of effective prevention and medications but approaches in the current management of photoaging are very limited. In the previous study, we found that a non-coding circular RNA circ_0011129 acts as a miR-6732-5p adsorption sponge to inhibit the reduction of type I collagen and the denaturation and accumulation of elastin in UVA-induced HDF cells photoaging model. However, in vivo instability and efficient delivery to the target cell of circRNA is a major challenge for its clinical application. Therefore, improving its stability and delivery efficiency are desired. In this study, we proposed a strategy of delivering circ_0011129 with small extracellular vesicles (sEVs) from human adipose-derived stem cells (hADSCs) to intervene in the photoaging process. The results showed that sEVs from hADSCs in 3D bioreactor culture (3D-sEVs) can prevent photoaging. Consequently, by overexpressing circ_0011129 in hADSCs, we successfully loaded it into 3D-sEVs (3D-circ-sEVs) and its protective effect was better. Our studies provide a novel approach to preventing skin photoaging, which has important clinical significance and application value for the development of non-coding RNA drugs to treat skin photoaging. We first screened out hADSCs-derived sEVs with excellent anti-oxidant effects. We then compared the sEVs collected from traditional 2D culture with 3D bioreactor culture. By miRNA-seq and GEO data analysis, we found that miRNAs in 3D-sEVs were enriched in cell activities related to apoptosis, cellular senescence, and inflammation. Subsequently, we prepared circ_0011129-loaded 3D-sEVs (3D-circ-sEVs) by overexpressing it in hADSCs for the treatment of photoaging in vitro. We proved that 3D-circ-sEVs can interfere with the process of cell photoaging and protect cells from UVA radiation damage, as well as in a H2O2-induced oxidative stress model.

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Circ-HSP90A expedites cell growth, stemness, and immune evasion in non-small cell lung cancer by regulating STAT3 signaling and PD-1/PD-L1 checkpoint

Cited by 17 publications

References 40 publications

Hsa_circ_0080608 Attenuates Lung Cancer Progression by Functioning as a Competitive Endogenous RNA to Regulate the miR-661/ADRA1A Pathway

Hsa_circ_0080608 Attenuates Lung Cancer Progression by Functioning as a Competitive Endogenous RNA to Regulate the miR-661/ADRA1A Pathway

Cancer‐derived non‐coding RNAs endow tumor microenvironment with immunosuppressive properties

Circ_0011129 Encapsulated by the Small Extracellular Vesicles Derived from Human Stem Cells Ameliorate Skin Photoaging

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