Exosome-derived circTRPS1 promotes malignant phenotype and CD8+ T cell exhaustion in bladder cancer microenvironments

Yang, Chen; Wu, Siqi; Mou, Zezhong; Zhou, Quan; Dai, Xiaoming; Ou, Yuxi; Chen, Xinan; Chen, Yi‐Ling; Xu, Chenyang; Hu, Yun; Zhang, Limin; Zou, Lina; Jin, Shengming; Hu, Jimeng; Mao, Shanhua; Jiang, Haowen

doi:10.1016/j.ymthe.2022.01.022

Cited by 100 publications

(66 citation statements)

References 46 publications

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“…The imbalance between ROS production and degradation can cause oxidative stress, resulting in energy depletion, DNA damage, protein carbonylation, and lipid oxidation, leading to various diseases and disorders [ 26 , 27 ]. The close relationship between circular RNAs and ROS suggests that circular RNAs play critical roles as a target in the treatment of tumor metabolism [ 28 – 30 ]. Focusing on circRNAs as emerging molecular propellants of CRC progression, we intended to determine the mechanisms underlying circular RNA-mediated development of CRC.…”

Section: Discussionmentioning

confidence: 99%

Upregulated circTMEM59 Inhibits Cell Growth and Metastasis by miR-668-3p/ID4 Axis in Colorectal Cancer

Feng

Wang

Huang

et al. 2022

Oxidative Medicine and Cellular Longevity

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The incidence and mortality of colorectal cancer (CRC) are ranked in the top three worldwide in 2020. Abundant studies have reported that circular RNAs (circRNAs) act critical roles in the genesis and development of tumors, including CRC. Nevertheless, the roles and detailed regulation mechanisms of circRNAs that are related to the initiation and development of CRC have not been fully found and clarified. This research primarily revealed that circTMEM59 was greatly downregulated in CRC tissues and cell lines via qRT-PCR. In addition, the decreased expression of circTMEM59 was closely related to adverse clinicopathological characteristics and the shorter survival time of CRC patients. Then, a further study found that the overexpression of circTMEM59 suppressed cell growth and accelerated the cell death of CRC via a series of experiments in vitro and in vivo. Furthermore, circTMEM59 also repressed the metastatic behaviors of CRC cells. Further study revealed that circTMEM59 played the role of competing endogenous RNAs (ceRNAs) by binding to miR-668-3p to increase the expression of inhibitor of DNA binding 4 (ID4) in CRC. In summary, the results of this study clarified the antitumor effects of circTMEM59/miR-668-3p/ID4 axis in CRC progression and provided potential therapeutic targets and clinical prognostic markers for CRC.

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Section: Discussionmentioning

confidence: 99%

Upregulated circTMEM59 Inhibits Cell Growth and Metastasis by miR-668-3p/ID4 Axis in Colorectal Cancer

Feng

Wang

Huang

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Moreover, high macrophage M2 infiltration and low CD8 T cells in the high-risk group of BCa were priorly demonstrated to be correlated with destitute response in immunotherapy (67). In BCa, exosome-originated circTRPS1 from tumor cells can regulate CD8+ T cell exhaustion and the balance of intracellular reactive oxygen species through the miR141-3p/GLS1 axis (33). Through single-cell RNA sequencing, Chen et al also illustrated that monocyte/ macrophages polarization toward M2 phenotype, LAMP3 + DC subgroup recruiting regulatory T cells, and inflammatory cancer-associated fibroblasts (iCAFs) in the tumor region, all potentially involve in the formation of an immune-suppressive TME and tumor progression, which is significantly associated with poor prognosis of BCa patients (68).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, many studies about the biological functions of circRNA in regulating tumor-infiltrating immune cells, including CD8+ T cell ( 33 , 34 ), cancer-associated fibroblasts ( 14 ), M2/M1 macrophages ( 35 , 36 ), and Treg cells ( 24 ), etc, have been investigated in diverse malignancies. Immunotherapy in BCa has shown promising results, but how to better figure out the heterogeneity of BCa is still a highly debated topic.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Identification of a dysregulated CircRNA-associated gene signature for predicting prognosis, immune landscape, and drug candidates in bladder cancer

Shen

Zhang

et al. 2022

Front. Oncol.

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Increasing evidences have demonstrated that circular RNA (circRNAs) plays a an essential regulatory role in initiation, progression and immunotherapy resistance of various cancers. However, circRNAs have rarely been studied in bladder cancer (BCa). The purpose of this research is to explore new circRNAs and their potential mechanisms in BCa. A novel ceRNA-regulated network, including 87 differentially expressed circRNAs (DE-circRNAs), 126 DE-miRNAs, and 217 DE-mRNAs was constructed to better understanding the biological processes using Cytoscape 3.7.1 based on our previously high-throughput circRNA sequencing and five GEO datasets. Subsequently, five randomly selected circRNAs (upregulated circ_0001681; downregulated circ_0000643, circ_0001798, circ_0006117 and circ_0067900) in 20 pairs of BCa and paracancerous tissues were confirmed using qRT-PCR. Functional analysis results determined that 772 GO functions and 32 KEGG pathways were enriched in the ceRNA network. Ten genes (PFKFB4, EDNRA, GSN, GAS1, PAPPA, DTL, TGFBI, PRSS8, RGS1 and TCF4) were selected for signature construction among the ceRNA network. The Human Protein Atlas (HPA) expression of these genes were consistent with the above sequencing data. Notably, the model was validated in multiple external datasets (GSE13507, GSE31684, GSE48075, IMvigor210 and GSE32894). The immune-infiltration was evaluated by 7 published algorithms (i.e., TIMER, CIBERSORT, CIBERSORT-ABS, QUANTISEQ, MCPCOUNTER, XCELL and EPIC). Next, Correlations between riskscore or risk groups and clinicopathological data, overall survival, recognized immunoregulatory cells or common chemotherapeutic agents of BCa patients were performed using wilcox rank test, chi-square test, cox regression and spearman’s correlation analysis; and, these results are significant. According to R package “GSVA” and “clusterProfiler”, the most significantly enriched HALLMARK and KEGG pathway was separately the ‘Epithelial Mesenchymal Transition’ and ‘Ecm Receptor Interaction’ in the high- vs. low-risk group. Additionally, the functional experiments in vitro also revealed that the overexpression of has_circ_0067900 significantly impaired the proliferation, migration, and invasion capacities of BCa cells. Collectively, the results of the current study provide a novel landscape of circRNA-associated ceRNA-regulated network in BCa. The ceRNA-associated gene model which was constructed presented a high predictive performance for the prognosis, immunotherapeutic responsiveness, and chemotherapeutic sensitivity of BCa. And, has_circ_0067900 was originally proposed as tumor suppressor for patients with BCa.

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“…In addition, the regulatory network among circHIPK3, LncGAS5 and miR-495 can promote Th2 differentiation in allergic rhinitis ( 149 ), and hsa_circ_0002594 and hsa_circ_0005519 can affect asthma by regulating CD4+ T cells ( 77 , 150 ). Moreover, N-methyladenosine-modified circIGF2BP3 was found to inhibit CD8+ T-cell responses and promote tumor immune evasion ( 151 ), while exogenous circTRPS1 was proven to be related to CD8+ T-cell exhaustion ( 152 ). In addition, Chen et al.…”

Section: Roles Of Circrnas In Immune-related Diseasesmentioning

confidence: 99%

Past, Present and Future: The Relationship Between Circular RNA and Immunity

Huang

et al. 2022

Front. Immunol.

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The immune system has evolved since the birth of humans. However, immune-related diseases have not yet been overcome due to the lack of expected indicators and targeting specificity of current medical technology, subjecting patients to very uncomfortable physical and mental experiences and high medical costs. Therefore, the requirements for treatments with higher specificity and indicative ability are raised. Fortunately, the discovery of and continuous research investigating circular RNAs (circRNAs) represent a promising method among numerous methods. Although circRNAs wear regarded as metabolic wastes when discovered, as a type of noncoding RNA (ncRNA) with a ring structure and wide distribution range in the human body, circRNAs shine brilliantly in medical research by virtue of their special nature and structure-determined functions, such as high stability, wide distribution, high detection sensitivity, acceptable reproducibility and individual differences. Based on research investigating the role of circRNAs in immunity, we systematically discuss the hotspots of the roles of circRNAs in immune-related diseases, including expression profile analyses, potential biomarker research, ncRNA axis/network construction, impacts on phenotypes, therapeutic target seeking, maintenance of nucleic acid stability and protein binding research. In addition, we summarize the current situation of and problems associated with circRNAs in immune research, highlight the applications and prospects of circRNAs in the treatment of immune-related diseases, and provide new insight into future directions and new strategies for laboratory research and clinical applications.

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Exosome-derived circTRPS1 promotes malignant phenotype and CD8+ T cell exhaustion in bladder cancer microenvironments

Cited by 100 publications

References 46 publications

Upregulated circTMEM59 Inhibits Cell Growth and Metastasis by miR-668-3p/ID4 Axis in Colorectal Cancer

Upregulated circTMEM59 Inhibits Cell Growth and Metastasis by miR-668-3p/ID4 Axis in Colorectal Cancer

Identification of a dysregulated CircRNA-associated gene signature for predicting prognosis, immune landscape, and drug candidates in bladder cancer

Past, Present and Future: The Relationship Between Circular RNA and Immunity

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