Mechanism of circRNA_4083 Circularization and Its Role in Regulating Cell Viability DOI Creative Commons
Wenhao Li, Ting Yang, Haojie Wang

и другие.

Animals, Год журнала: 2025, Номер 15(11), С. 1527 - 1527

Опубликована: Май 23, 2025

Circular RNAs (circRNAs), a class of covalently closed non-coding RNAs, are pivotal regulators gene expression and contributors to disease pathogenesis. This study elucidated the biogenesis, functional significance, regulatory network circRNA_4083, novel exon-derived circRNA originating from exons 22 23 MSH3 in chicken. Through comprehensive molecular characterization—including Sanger sequencing, RNase R digestion assays, subcellular localization—we confirmed robust stability predominant cytoplasmic localization circRNA_4083 across diverse chicken tissues. Mechanistic investigations revealed that reverse complementary sequences within flanking intronic regions indispensable for its circularization, as demonstrated by overexpression plasmids (#1–#4) DF-1 cells. Functional analyses significantly inhibited cell apoptosis increased cellular viability. Integrative bioinformatics approaches predicted competing endogenous RNA (ceRNA) comprising 12 miRNAs 2132 target genes (FDR < 0.05), with significant enrichment pathways critical genomic stability, including non-homologous end joining (NHEJ) ubiquitin-mediated proteolysis. These findings position key modulator viability integrity, potential implications avian leukosis virus-J (ALV-J) pathogenesis resistance breeding strategies. work advances our understanding circRNA-driven mechanisms species underscores their relevance poultry health.

Язык: Английский

CircHIPK2 Contributes Cell Growth in Intestinal Epithelial of Colitis and Colorectal Cancer through Promoting TAZ Translation DOI Creative Commons
Xixi Zeng,

Jielin Tang,

Qian Zhang

и другие.

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Июль 9, 2024

Colorectal cancer (CRC) and inflammatory bowel disease (IBD) are escalating global health concerns. Despite their distinct clinical presentations, both disorders share intricate genetic molecular interactions. The Hippo signaling pathway plays a crucial role in regulating cell processes is implicated the pathogenesis of IBD CRC. Circular RNAs (circRNAs) have gained attention for roles various diseases, including However, comprehensive understanding specific circRNAs involved CRC, functional lacking. Here, it found that circHIPK2 (hsa_circRNA_104507) bona fide circRNA consistently upregulated CRC suggesting its potential as biomarker. Furthermore, silencing suppressed growth cells vitro vivo. Interestingly, decreased circHipk2 potentiated dextran sulfate sodium (DSS)-induced colitis but alleviated colitis-associated tumorigenesis. Most significantly, mechanistic investigations further unveil circHIPK2, mediated by FUS, interacting with EIF4A3 to promote translation TAZ, ultimately increasing transcription downstream target genes CCN1 CCN2. Taken together, emerges key player shared mechanisms modulating pathway. CircHIPK2-EIF4A3 axis contributes intestinal epithelial enhancing TAZ translation.

Язык: Английский

Процитировано

9
Hypoxia-induced circPLOD2a/b promotes the aggressiveness of glioblastoma by suppressing XIRP1 through binding to HuR DOI Creative Commons
An-Lu Yu, Yiqi Wang, Chao Duan

и другие.

Communications Biology, Год журнала: 2025, Номер 8(1)

Опубликована: Янв. 17, 2025

Hypoxia is a common feature of glioblastoma (GBM). Circular RNAs (circRNAs) are identified as regulators in cancers. However, the role circRNAs GBM remains elusive. Here, circPLOD2a and circPLOD2b, spliced from same parental gene PLOD2, hypoxia-responsive circRNAs. Overexpression b enhance while knockdown inhibit cell aggressiveness. The protein partners downstream molecules were investigated by RNA-pulldown, mass spectrometry RNA-seq. Mechanistically, HIF1α induces expression b, which competitively bind to HuR, causing degradation XIRP1 vitro vivo. Clinical data demonstrate highly expressed negatively correlated with XIRP1, whose lower associates higher glioma grade worse prognosis. In conclusion, hypoxia-induced oncogenic tumour aggressiveness through attenuating interaction between HuR cells may be potential therapeutic targets for this disease.

Язык: Английский

Процитировано

1
EIF4A3-Mediated circ_0008126 Inhibits the Progression and Metastasis of Gastric Cancer by Modulating the APC/β-Catenin Pathway DOI Open Access

Z Wang,

Wenxing Chen, Ziwei Wang

и другие.

Cancers, Год журнала: 2025, Номер 17(2), С. 253 - 253

Опубликована: Янв. 14, 2025

Background: Mounting evidence exhibits circRNAs as critical regulators in the progression of many tumors. The regulatory function and potential mechanism by which circ_0008126 gastric cancer (GC) is unknown. Methods: To validate analyze expression levels clinical values GC patients, biological phenotypes were investigated vitro vivo. roles effects on miR-502-5p, EIF4A3, APC cells explored using rescue experiment, RNA stability assay, pull-down, dual-luciferase reporter, immunoprecipitation (RIP), FISH, immunofluorescence (IF), TOP/Flash FOP/Flash assays. Results: Circ_0008126 prominently down-regulated tissues cells. Importantly, low was relevant to more lymphatic metastasis, advanced TNM stage, poor survival period patients with GC. Functionally, inhibited cell proliferative activity, metastatic ability, epithelial-mesenchymal transition (EMT) Mechanistically, we verified that EIF4A3 can mediate formation circ_0008126, could competitively bind miR-502-5p alleviate its role effect APC, thus inactivating β-catenin pathway Additionally, determined increase mRNA interacting cytoplasmic protein then enhancing expression. Conclusions: These data demonstrate EIF4A3-mediated regulate inactivate partly binding inhibiting tumorigenesis development

Язык: Английский

Процитировано

0
A Novel 167‐Amino Acid Protein Encoded by CircPCSK6 Inhibits Intrahepatic Cholangiocarcinoma Progression via IKBα Ubiquitination DOI Creative Commons
Canghai Guan,

Gao Jianjun,

Xinlei Zou

и другие.

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 21, 2025

Abstract Intrahepatic cholangiocarcinoma (ICC), a formidable challenge in oncology, demands innovative biomarkers and therapeutic targets. This research highlights the importance of circular RNA (circRNA) circPCSK6 its peptide derivative circPCSK6‐167aa ICC. CircPCSK6 is significantly downregulated both ICC patients mouse primary models, lower expression linked to adverse prognosis, highlighting pivotal role pathogenesis. Functionally, this study elucidates regulatory effect on IκBα ubiquitination within NF‐κB pathway, which mediated by competitive binding E3 ligase RBBP6. complex interaction leads reduced activation thereby curbing tumor cell proliferation, migration, invasion, stemness, hepatic‐lung metastasis vivo. groundbreaking discovery expands understanding circRNA‐driven tumorigenesis through atypical signaling pathways. Additionally, investigation identified EIF4A3 as detrimental regulator circPCSK6, exacerbating malignancy. Importantly, leveraging patient‐derived xenograft (PDX), organoids, organoid‐derived PDX higher levels enhance sensitivity gemcitabine, indicating potential improve effectiveness chemotherapy. These insights emphasize promise targeting circPCSK6‐167aa, offering vital biological clinical directions for developing cutting‐edge approaches, thus revealing strategies targets future treatments.

Язык: Английский

Процитировано

0
Mesenchymal Stem Cells Armed with DNA Nanorobots as a Modality for Combination Therapy of Inflammatory Bowel Disease DOI

Hongxiu Yuan,

Gang Wang, Fangbo Zou

и другие.

ACS Applied Materials & Interfaces, Год журнала: 2025, Номер unknown

Опубликована: Фев. 28, 2025

Therapeutic strategies that can target multilevel immunoregulatory pathways in inflammatory bowel disease (IBD) and efficiently the site of inflammation are expected to greatly enhance therapeutic efficacy. Here, we have developed a DNA nanorobot-armed bidirectional resistant mesenchymal stem cell (MSC) for IBD treatment, which blocks lymphocyte infiltration at by inhibition integrin-ligand inter-recognition via aptamer-hands. And this strategy induce MSC homing immunomodulation tissue repair. Herein, nanorobot, tetrahedral (TDN) serves as communication bridge, Integrin α4 VCAM 1 aptamers equipped two vertices TDN, other cholesterol TDN used immobilization on MSC. In murine colitis models, tail vein-injected preferentially rapidly accumulated inflamed colon been more effective reducing colonic than pure or inhibitors. The proposed work has minimal systemic side effects holds promise subgroup patients who do not respond single anti-inflammatory therapies.

Язык: Английский

Процитировано

0
Circular RNAs in inflammatory bowel disease: a review of mechanisms, biomarkers and therapeutic potential DOI Creative Commons
Le Yang, Huahui Li, Min Tang

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 24, 2025

Inflammatory bowel disease (IBD) is an autoimmune of unknown etiology characterized by recurrent chronic inflammation the gastrointestinal tract. The incidence IBD increasing and has become a focus research on digestive diseases. Despite advances in understanding its multifactorial etiology, including genetic predisposition, microbiome dysbiosis, immune dysregulation. However, molecular mechanisms driving pathogenesis remain incompletely elucidated. Circular RNA (circRNA) stable single-stranded with closed-loop structure conserved nature. circRNA possesses multiple functions, such as adsorption microRNAs RNA-binding proteins, involved regulation gene splicing transcription, well protein translation. circRNAs progression their clinical potential biomarkers or therapeutic targets are yet to be systematically explored. In this review, we comprehensively synthesize recent advancements related IBD, integrating evidence from vitro, vivo, studies. We analyze aberrant expression profiles tissues (e.g., intestinal mucosa, peripheral blood, exosomes) discuss mechanism action contributions inflammation, epithelial barrier dysfunction, autophagy, fibrosis, colitis-associated cancer (CAC). Furthermore, evaluate methodologies for detection modulation, interference, viral vector delivery, PLGA MSs delivery system strategies. This review highlights circRNA-focused strategies diagnosis treatment offering scientific foundation advancing precision medicine management.

Язык: Английский

Процитировано

0
circRNA/TLR interaction: key players in immune regulation and autoimmune diseases DOI
Chou‐Yi Hsu,

Alaa Khalaf Bediwi,

Ahmed Hussein Zwamel

и другие.

Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2025, Номер unknown

Опубликована: Май 6, 2025

Язык: Английский

Процитировано

0
Intestinal epithelial cells in health and disease DOI

Chenchen An,

Chonggui Jiang, Wenli Pei

и другие.

Tissue Barriers, Год журнала: 2025, Номер unknown

Опубликована: Май 22, 2025

This comprehensive review delves into the pivotal role of intestinal epithelial cells in context various diseases. It provides an in-depth analysis diverse types and functions these cells, explores influence multiple signaling pathways on their differentiation, elucidates critical roles a spectrum The significance gastrointestinal tract maintaining overall health is extremely important cannot be exaggerated. complex elongated organ acts as crucial link between internal external environments, making it vulnerable to harmful influences. Preserving normal structure function gut essential for well-being. Intestinal serve primary defense mechanism within play preventing substances from infiltrating body. As main components digestive system, they not only participate absorption secretion nutrients maintenance barrier but also immune defense. Therefore, vital importance health.

Язык: Английский

Процитировано

0
Mechanism of circRNA_4083 Circularization and Its Role in Regulating Cell Viability DOI Creative Commons
Wenhao Li, Ting Yang, Haojie Wang

и другие.

Animals, Год журнала: 2025, Номер 15(11), С. 1527 - 1527

Опубликована: Май 23, 2025

Circular RNAs (circRNAs), a class of covalently closed non-coding RNAs, are pivotal regulators gene expression and contributors to disease pathogenesis. This study elucidated the biogenesis, functional significance, regulatory network circRNA_4083, novel exon-derived circRNA originating from exons 22 23 MSH3 in chicken. Through comprehensive molecular characterization—including Sanger sequencing, RNase R digestion assays, subcellular localization—we confirmed robust stability predominant cytoplasmic localization circRNA_4083 across diverse chicken tissues. Mechanistic investigations revealed that reverse complementary sequences within flanking intronic regions indispensable for its circularization, as demonstrated by overexpression plasmids (#1–#4) DF-1 cells. Functional analyses significantly inhibited cell apoptosis increased cellular viability. Integrative bioinformatics approaches predicted competing endogenous RNA (ceRNA) comprising 12 miRNAs 2132 target genes (FDR < 0.05), with significant enrichment pathways critical genomic stability, including non-homologous end joining (NHEJ) ubiquitin-mediated proteolysis. These findings position key modulator viability integrity, potential implications avian leukosis virus-J (ALV-J) pathogenesis resistance breeding strategies. work advances our understanding circRNA-driven mechanisms species underscores their relevance poultry health.

Язык: Английский

Процитировано

0