Mechanisms of immune checkpoint inhibitors: insights into the regulation of circular RNAS involved in cancer hallmarks

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 4, 2024

Abstract Current treatment strategies for cancer, especially advanced are limited and unsatisfactory. One of the most substantial advances in cancer therapy, last decades, was discovery a new layer immunotherapy approach, immune checkpoint inhibitors (ICIs), which can specifically activate cells by targeting checkpoints. Immune checkpoints type immunosuppressive molecules expressed on cells, regulate degree activation avoid autoimmune responses. ICIs, such as anti-PD-1/PD-L1 drugs, has shown inspiring efficacy broad applicability across various cancers. Unfortunately, not all patients benefit remarkably from overall response rates to ICIs remain relatively low types. Moreover, primary acquired resistance pose serious challenges clinical application immunotherapy. Thus, deeper understanding molecular biological properties regulatory mechanisms is urgently needed improve options fo r current therapies. Recently, circular RNAs (circRNAs) have attracted increasing attention, only due their involvement aspects hallmarks, but also impact shaping tumor microenvironment. In this review, we systematically summarize status existing roles circRNAs Meanwhile, aim settle issue an evidence-oriented manner that involved hallmarks effects

Language: Английский

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Hijacking and rewiring of host CircRNA/miRNA/mRNA competitive endogenous RNA (ceRNA) regulatory networks by oncoviruses during development of viral cancers

Reviews in Medical Virology, Journal Year: 2024, Volume and Issue: 34(2)

Published: March 1, 2024

A significant portion of human cancers are caused by oncoviruses (12%-25%). Oncoviruses employ various strategies to promote their replication and induce tumourigenesis in host cells, one which involves modifying the gene expression patterns leading rewiring genes resulting changes cellular processes signalling pathways. In recent studies, a specific mode regulation known as circular RNA (circRNA)-mediated competing endogenous (ceRNA) networks has emerged key player this context. CircRNAs, class non-coding molecules, can interact with other such mRNAs microRNAs (miRNAs), through process ceRNA crosstalk. This interaction occurs when circRNAs, acting sponges, sequester miRNAs, thereby preventing them from binding target modulating expression. By cell genome, have ability manipulate activity influencing that profoundly impact proliferation, differentiation, apoptosis, immune responses. review focuses on comprehensive evaluation latest findings involvement virus-induced reprogramming circRNA-mediated development pathophysiology viral cancers, including cervical cancer, gastric nasopharyngeal carcinoma, Kaposi's sarcoma, hepatocellular diffuse large B lymphoma. Understanding these mechanisms improve our knowledge how contribute identify potential targets for developing optimised therapies diagnostic tools cancers.

Language: Английский

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Molecular aspects of cervical cancer: a pathogenesis update

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: March 19, 2024

Cervical cancer (CC) is a significant health problem, especially in low-income countries. Functional studies on the human papillomavirus have generated essential advances knowledge of CC. However, many unanswered questions remain. This mini-review discusses latest results CC pathogenesis, HPV oncogenesis, and molecular changes identified through next-generation technologies. Interestingly, percentage samples with genome integrations correlates degree cervical lesions, suggesting role development Also, new functions been described for viral oncoproteins E5, E6, E7, resulting acquisition maintenance hallmarks, including proliferation, immune response evasion, apoptosis, genomic instability. Remarkably, E5 oncoprotein affects signaling pathways involved expression interferon-induced genes EGFR-induced while E6 E7 regulate DNA damage repair cell cycle continuity pathways. Furthermore, technologies provide vast amounts information, increasing our genome, transcriptome, proteome, metabolome, epigenome These novel traits associated disease susceptibility, progression, treatment response, survival as potential biomarkers therapeutic targets.

Language: Английский

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Targeted regulation of miR-154-5p/Cullin2 pathway by hsa_circ_TRIM22 in promoting human papillomavirus 16 positive cervical cancer progression

Journal of Cancer, Journal Year: 2024, Volume and Issue: 15(8), P. 2137 - 2146

Published: Jan. 1, 2024

Background.Tripartite motif-containing 22 (TRIM22) is characterized by a canonical RING domain with ubiquitin E3 ligase activity and closely associated tumorigenesis.As product of TRIM22 transcription, whether hsa_circ_TRIM22 has function regulating tumorigenesis unclear.Thus, we aimed to explore the role mechanism in human papillomavirus (HPV) 16 positive cervical cancer (CC).Methods.We collected HPV16-positive tissues including chronic cervicitis, high-grade squamous intraepithelial lesions (HSIL), low-grade (LSIL), CC, along CC cell lines detect level using real-time fluorescence quantitative polymerase chain reaction (RT-qPCR).Hsa_circ_TRIM22 was silenced specific short hairpin ribonucleic acid (shRNA) functional assays were performed thereafter.Mechanistically, targeting regulatory relationship between miR-154-5p confirmed luciferase report assay rescue experiments.Results.We found expression significantly higher cells tissues.Further, knockdown inhibited migration, proliferation, invasiveness, enhanced apoptosis, slowed cycle.Mechanistically, could bind prevent from reducing levels Cullin2 (CUL2).Notably, application inhibitor rescued hsa_circ_TRIM22-mediated tumorigenesis.Conclusions.Our observations suggest upregulated promotes progression miR-154-5p/CUL2 axis, thereby serving as promising candidate for diagnosis treatments CC.

Language: Английский

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MicroRNA-154-5p suppresses cervical carcinoma growth and metastasis by silencing Cullin2 in vitro and in vivo

PeerJ, Journal Year: 2023, Volume and Issue: 11, P. e15641 - e15641

Published: June 27, 2023

Background MicroRNA-154-5p (miR-154-5p) plays a role in tumorigenesis diverse human malignancies. Nevertheless, little is known about the mechanism by which miR-154-5p alters growth and metastasis of cervical cancer. This research aimed to analyze pathology cancer vitro vivo . Methods The level papillomavirus 16 positive cells was examined real-time quantitative polymerase chain reaction. Bioinformatics predicted downstream targets potential functions miR-154-5p. Furthermore, lentiviral technology used construct SiHa cell lines with stable up- down-expression levels Its differential expression effects on progress were analyzed using culture animal models. Results MiR-154-5p showed low cells. Overexpression could markedly inhibit proliferation, migration, colony formation ability cells, concomitantly leading G1 arrest cycle, while silencing triggered opposite results. Meanwhile, overexpression restrained CUL2 Additionally, reduced level, influenced effect In conclusion, directly CUL2.

Language: Английский

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Targeted regulation of miR-154-5p/Cullin-2 pathway by hsa_circ_0000276 in human papillomavirus type 16 positive cervical cancer cells

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 7, 2023

Abstract Purpose To investigate the role of targeting and silencing miR-154-5p by hsa_circ_0000276 in regulating Cullin-2 (CUL2) expression human papillomavirus type 16 (HPV16)-positive cervical cancer (CC) cells. Methods Cervical tissues individuals with normal cervix (NC), low-grade squamous intraepithelial lesions (LSIL), high-grade (HSIL), HPV16-CC were collected. level cell lines was determined using real-time fluorescence quantitative PCR (qRT-PCR). A shRNA vector constructed for circular RNA—hsa_circ_0000276. CC cells transfected sh-hsa_circ_0000276 or sh-NC. The counting kit-8, scratch healing, transwell migration assays, flow cytometry used to assess proliferation, migration, invasiveness, cycle distribution, apoptosis cells, respectively. Mechanistically, regulatory activity between confirmed Dual-Luciferase Reporter gene assay rescue experiments. Results significantly higher Functionally, knockdown decreased slowed cycle, enhanced apoptosis. could bind prevent from reducing levels CUL2. Notably, application inhibitor rescued hsa_circ_0000276-mediated tumorigenesis. Conclusion is upregulated HPV16-positive promotes progression miR-154-5p/CUL2 pathway, suggesting that it may be a target treatment.

Language: Английский

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