Emerging Role of Circular RNAs in Hepatocellular Carcinoma Immunotherapy DOI Open Access
Tasneem Abaza, Mostafa K. Abd El‐Aziz,

Kerolos Ashraf Daniel

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(22), P. 16484 - 16484

Published: Nov. 18, 2023

Hepatocellular carcinoma (HCC) is a highly fatal malignancy with limited therapeutic options and high recurrence rates. Recently, immunotherapeutic agents such as immune checkpoint inhibitors (ICIs) have emerged new paradigm shift in oncology. ICIs, programmed cell death protein 1 (PD-1) inhibitors, provided source of hope for patients advanced HCC. Yet, the eligibility criteria HCC ICIs are still missing piece puzzle. Circular RNAs (circRNAs) recently class non-coding that play fundamental role cancer pathogenesis. Structurally, circRNAs resistant to exonucleolytic degradation longer half-life than their linear counterparts. Functionally, possess capability influence various facets tumor microenvironment, especially at tumor–immune synapse. Notably, been observed control expression molecules within cells, potentially impeding effectiveness ICIs. Therefore, this renders them potential cancer-immune biomarkers diagnosis, prognosis, regimen determinants. In review, authors shed light on structure functional roles and, most importantly, highlight promising immunomodulation

Language: Английский

Epigenetics of glioblastoma multiforme: From molecular mechanisms to therapeutic approaches DOI
Md. Sahab Uddin, Abdullah Al Mamun, Badrah S. Alghamdi

et al.

Seminars in Cancer Biology, Journal Year: 2020, Volume and Issue: 83, P. 100 - 120

Published: Dec. 25, 2020

Language: Английский

Citations

141
Amplification of spatially isolated adenosine pathway by tumor–macrophage interaction induces anti-PD1 resistance in hepatocellular carcinoma DOI Creative Commons

Jia‐Cheng Lu,

Pengfei Zhang, Xiaoyong Huang

et al.

Journal of Hematology & Oncology, Journal Year: 2021, Volume and Issue: 14(1)

Published: Nov. 27, 2021

Abstract Background Immune checkpoint blockade resistance narrows the efficacy of cancer immunotherapies, but underlying mechanism remains elusive. Delineating inherent mechanisms anti-PD1 is important to improve outcome patients with advanced HCC. Method The level cricTMEM181 was measured in HCC therapy by RNA sequencing and then confirmed qPCR Sanger sequencing. status tumor microenvironment or mice models evaluated flow cytometry IHC. Exosomes from cell lines were isolated ultracentrifugation, their internalization macrophage immunofluorescence. HCC-derived exosomal circTMEM181 SILAC, FISH immunoprecipitation. ATP–ADO pathway amplified HCC–macrophage interaction through ATP, AMP ADO measurement macrophage-specific CD39 knockout mice. role its clinical significance also determined our retrospective cohorts. Results Here, we found that elevated hepatocellular carcinoma (HCC) responding poorly a poor prognosis after operation. Moreover, high favored immunosuppressive endowed Mechanistically, sponged miR-488-3p upregulated expression macrophages. Using pharmacologic approaches, revealed novel mode We discovered cell-specific macrophages CD73 cells synergistically activated eATP–adenosine produced more adenosine, thereby impairing CD8 + T function driving resistance. Conclusion In summary, contributes immunosuppression elevating expression, inhibiting ATP–adenosine targeting on can rescue Graphical

Language: Английский

Citations

109
Going circular: history, present, and future of circRNAs in cancer DOI Creative Commons
Giuseppina Pisignano, David C. Michael, Tanvi H. Visal

et al.

Oncogene, Journal Year: 2023, Volume and Issue: 42(38), P. 2783 - 2800

Published: Aug. 16, 2023

Abstract To date, thousands of highly abundant and conserved single-stranded RNA molecules shaped into ring structures (circRNAs) have been identified. CircRNAs are multifunctional that shown to regulate gene expression transcriptionally post-transcriptionally exhibit distinct tissue- development-specific patterns associated with a variety normal disease conditions, including cancer pathogenesis. Over the past years, due their intrinsic stability resistance ribonucleases, particular attention has drawn use as reliable diagnostic prognostic biomarkers in diagnosis, treatment, prevention. However, there some critical caveats utility clinic. Their circular shape limits annotation complete functional elucidation is lacking. This makes detection biomedical application still challenging. Herein, we review current knowledge circRNA biogenesis function, involvement tumorigenesis potential cancer-targeted therapy.

Language: Английский

Citations

106
A novel peptide encoded by N6-methyladenosine modified circMAP3K4 prevents apoptosis in hepatocellular carcinoma DOI Creative Commons
Jin‐Ling Duan, Wei Chen, Juanjuan Xie

et al.

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: April 2, 2022

Circular RNAs (circRNAs) regulate various biological activities and have been shown to play crucial roles in hepatocellular carcinoma (HCC) progression. However, only a few coding circRNAs identified cancers, their HCC remain elusive. This study aimed identify explore function HCC.

Language: Английский

Citations

102
Exosomal circRNA: emerging insights into cancer progression and clinical application potential DOI Creative Commons
Fan Zhang, Jiajia Jiang, Hui Qian

et al.

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: June 26, 2023

Abstract Exosomal circRNA serves a novel genetic information molecule, facilitating communication between tumor cells and microenvironmental cells, such as immune fibroblasts, other components, thereby regulating critical aspects of cancer progression including escape, angiogenesis, metabolism, drug resistance, proliferation metastasis. Interestingly, microenvironment have new findings in influencing escape mediated by the release exosomal circRNA. Given intrinsic stability, abundance, broad distribution circRNAs, they represent excellent diagnostic prognostic biomarkers for liquid biopsy. Moreover, artificially synthesized circRNAs may open up possibilities therapy, potentially bolstered nanoparticles or plant exosome delivery strategies. In this review, we summarize functions underlying mechanisms cell non-tumor cell-derived progression, with special focus on their roles immunity metabolism. Finally, examine potential application therapeutic targets, highlighting promise clinical use.

Language: Английский

Citations

99
Immune checkpoint inhibitor resistance in hepatocellular carcinoma DOI

Zhijie Wang,

Yichuan Wang, Peng Gao

et al.

Cancer Letters, Journal Year: 2022, Volume and Issue: 555, P. 216038 - 216038

Published: Dec. 16, 2022

Language: Английский

Citations

90
Extracellular Vesicles in Cancer Drug Resistance: Roles, Mechanisms, and Implications DOI Creative Commons

Yang Qiu-rong,

Jing Xu, Jianmei Gu

et al.

Advanced Science, Journal Year: 2022, Volume and Issue: 9(34)

Published: Oct. 17, 2022

Abstract Extracellular vesicles (EVs) are cell‐derived nanosized that mediate cell‐to‐cell communication via transporting bioactive molecules and thus critically involved in various physiological pathological conditions. EVs contribute to different aspects of cancer progression, such as growth, angiogenesis, metastasis, immune evasion, drug resistance. induce the resistance cells chemotherapy, radiotherapy, targeted therapy, antiangiogenesis immunotherapy by transferring specific cargos affect efflux regulate signaling pathways associated with epithelial‐mesenchymal transition, autophagy, metabolism, stemness. In addition, modulate reciprocal interaction between noncancer tumor microenvironment (TME) develop therapy detectable many biofluids patients, regarded novel biomarkers for monitoring response predicting prognosis. Moreover, suggested promising targets engineered nanovehicles deliver drugs overcoming therapy. this review, biological roles their mechanisms action summarized. The preclinical studies on using also discussed.

Language: Английский

Citations

86
Cancer exosomes and natural killer cells dysfunction: biological roles, clinical significance and implications for immunotherapy DOI Creative Commons
Reza Hosseini, Hamzeh Sarvnaz, Maedeh Arabpour

et al.

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Jan. 14, 2022

Abstract Tumor-derived exosomes (TDEs) play pivotal roles in several aspects of cancer biology. It is now evident that TDEs also favor tumor growth by negatively affecting anti-tumor immunity. As important sentinels immune surveillance system, natural killer (NK) cells can recognize malignant very early and counteract the development metastasis without a need for additional activation. Based on this rationale, adoptive transfer ex vivo expanded NK cells/NK cell lines, such as NK-92 cells, has attracted great attention widely studied promising immunotherapy treatment. However, exploiting various strategies, including secretion exosomes, are able to subvert responses. This paper reviews cancer-induced impairments with mechanistic insights. The clinical significance potential approaches nullify effects discussed.

Language: Английский

Citations

81
Circular RNA ANAPC7 Inhibits Tumor Growth and Muscle Wasting via PHLPP2–AKT–TGF-β Signaling Axis in Pancreatic Cancer DOI Creative Commons
Xiuhui Shi, Jingxuan Yang, Mingyang Liu

et al.

Gastroenterology, Journal Year: 2022, Volume and Issue: 162(7), P. 2004 - 2017.e2

Published: Feb. 14, 2022

Background & AimsPancreatic cancer has the highest prevalence of cancer-associated cachexia among all cancers. ZIP4 promotes pancreatic progression by regulating oncogenic miR-373, and perturbation circular RNAs (circRNAs) is associated with aggressiveness. This study aimed to identify circRNAs involved in ZIP4/miR-373–driven growth decipher underlying mechanism.MethodsDifferentially expressed potential targets microRNA were identified through silico analysis. The RNA interactions determined means biotinylated pulldown, immunoprecipitation, luciferase reporter assays. function circRNA ZIP4–miR-373 signaling axis examined human cells, 3-dimensional spheroids organoids, mouse models, clinical specimens. Mouse skeletal muscles analyzed histology.ResultsWe circANAPC7 as a sponge for which inhibited tumor muscle wasting vitro vivo. Mechanistic studies showed that PHLPP2 downstream target ZIP4/miR-373. CircANAPC7 functions PHLPP2-mediated dephosphorylation AKT, thus suppressing cell proliferation down-regulating cyclin D1 inhibiting via decreasing secretion transforming factor–β STAT5. We further demonstrated induced CREB, zinc-dependent transcription factor activated ZIP4, thereby forming CREB–miR-373–PHLPP2 feed-forward loop regulate cachexia.ConclusionThis novel suppressor, axis, leading AKT dephosphorylation, down-regulation suppress cancer. Pancreatic mechanism. Differentially histology. cachexia.

Language: Английский

Citations

80
The circular RNA circHMGB2 drives immunosuppression and anti-PD-1 resistance in lung adenocarcinomas and squamous cell carcinomas via the miR-181a-5p/CARM1 axis DOI Creative Commons

Ling-Xian Zhang,

Jian Gao, Xiang Long

et al.

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: May 7, 2022

Abstract Background Previous studies have confirmed the oncogenic role of HMGB2 in various cancers, but biological functions HMGB2-derived circRNAs remain unknown. Thus, we intended to investigate potential lung adenocarcinomas (LUAD) and squamous cell carcinomas (LUSC). Methods The expression profiles LUAD LUSC tissues matched normal were assessed using qRT–PCR. circHMGB2 progression was determined vitro by Transwell, CCK-8, flow cytometry immunohistochemistry assays, as well vivo an immunocompetent mouse model a humanized model. In addition, circRNA precipitation luciferase reporter assays RNA pulldown performed explore underlying mechanism which promotes anti-PD-1 resistance LUSC. Results (hsa_circ_0071452) significantly upregulated NSCLC tissues, survival analysis identified independent indicator poor prognosis patients. We found that exerted mild effect on proliferation cells, substantially reshaped tumor microenvironment contributing exhaustion antitumor immunity Mechanistically, relieves inhibition downstream CARM1 sponging miR-181a-5p, thus inactivating type 1 interferon response Moreover, upregulation decreased efficacy therapy, revealed combination inhibitor EZM2302 antibody promising synergistic effects preclinical Conclusion overexpression mainly reshaping regulating This study provides new strategy for treatment.

Language: Английский

Citations

78