PIWI-interacting RNA-YBX1 inhibits proliferation and metastasis by the MAPK signaling pathway via YBX1 in triple-negative breast cancer

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Jan. 5, 2024

Abstract Breast cancer is the second leading cause of death in women worldwide, with triple-negative breast (TNBC) having worst prognosis. Although there are numerous studies on TNBC, no effective treatment for it, and it still a major problem today. Studies PIWI-interacting RNAs (piRNAs) increasing investigating mechanism piRNAs proliferation metastasis TNBC may lead to new potential targets. Here, we identified novel piRNA, piR-YBX1, which was downregulated compared matched normal tissue. Overexpression piR-YBX1 significantly inhibited proliferation, migration, invasion ability cells both vivo vitro. Mechanistically, could bind directly mRNA Y-box binding protein 1 ( YBX1 ) overexpression levels, while function be partly rescued by YBX1. In addition, RAF1 key molecule MAPK signaling pathway, p-MEK p-ERK1/2, can reverted conclusion, our findings discovered that piR-YBX1/YBX1/MAPK axis suppresses therefore has an therapeutic agent cancer.

Language: Английский

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CircRNA‐associated ceRNA regulatory networks as emerging mechanisms governing the development and biophysiopathology of epilepsy

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(4)

Published: April 1, 2024

Abstract The etiology of epilepsy is ascribed to the synchronized aberrant neuronal activity within brain. Circular RNAs (circRNAs), a class non‐coding characterized by their circular structures and covalent linkage, exert substantial influence on this phenomenon. CircRNAs possess stereotyped replication, transience, repetitiveness, paroxysm. Additionally, MicroRNA (miRNA) plays crucial role in regulation diverse pathological processes, including epilepsy. CircRNA particular significance due its ability function as competing endogenous RNA, thereby sequestering or inhibiting miRNA through binding target mRNA. Our review primarily concentrates elucidating functional roles, well underlying mechanisms, circRNA–miRNA–mRNA networks it explores potential utility these for early detection therapeutic intervention.

Language: Английский

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Isoliquiritigenin inhibits circ0030018 to suppress glioma tumorigenesis via the miR‐1236/HER2 signaling pathway

MedComm, Journal Year: 2023, Volume and Issue: 4(3)

Published: May 26, 2023

In the central nervous system diseases, glioma is one of most common malignancies around world. Despite recent improvements in therapies for glioma, prognosis some high-risk remains poor. isoliquiritigenin (ISL) reported to have antioxidative and antitumor activities. However, potential mechanisms between ISL circle RNAs (circRNAs) tumorigenesis process not yet been reported. Here, we treated cells with ISL, circRNA expression levels were detected. Circ0030018 was found significantly downregulated by ISL. Therefore, explored circ0030018 profiles functions finding that evidently overexpressed cell lines. Colony formation, CCK-8, transwell assay made clear silencing dramatically cut down growth invasion. Moreover, ROS level detected find silence remarkably enhanced oxidative stress glioma. Mechanism studies conducted investigate underlying basis function unveiling realized its partially through miR-1236/HER2 signaling conclusion, our study investigated roles on circ0030018/miR-1236/HER2 pathway progression. could act as prospective biologic signature or therapeutic target

Language: Английский

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circROBO1 promotes prostate cancer growth and enzalutamide resistance via accelerating glycolysis

Journal of Cancer, Journal Year: 2023, Volume and Issue: 14(13), P. 2574 - 2584

Published: Jan. 1, 2023

Background and aim:As non-coding RNAs, circular RNAs (circRNAs) contribute to the progression of malignancies by regulating various biological processes.In prostate cancer, however, there is still a lack understanding regarding potential molecular pathways roles circRNAs.Methods: Loss-off function experiments were performed investigate circRNA in cancer.Western blot, qRT-PCR, IHC assay used examine expression level different genes or circRNAs.Further biology conducted uncover mechanism underlying cancer using dual luciferase reporter RNA immunoprecipitation (RIP) assays.Results: A novel (hsa_circ_0124696, named circROBO1) was identified as significantly upregulated both cells tissues.Suppression circROBO1 attenuated proliferation cells.In addition, we found that knockdown remarkably increased sensitivity enzalutamide treatment.A deceleration glycolysis rate observed after inhibition circROBO1, which could suppress growth overcome resistance enzalutamide.Our results revealed promotes via accelerating glycolysis. Conclusion:Our study role circROBO1-miR-556-5p-PGK1 axis therapeutic target cancer.

Language: Английский

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The potential role and mechanism of circRNA/miRNA axis in cholesterol synthesis

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(9), P. 2879 - 2896

Published: Jan. 1, 2023

Cholesterol levels are an initiating risk factor for atherosclerosis. Many genes play a central role in cholesterol synthesis, including HMGCR, SQLE, HMGCS1, FDFT1, LSS, MVK, PMK, MVD, FDPS, CYP51, TM7SF2, LBR, MSMO1, NSDHL, HSD17B7, DHCR24, EBP, SC5D, DHCR7, IDI1/2. Especially, and EBP promising therapeutic targets drug development due to many drugs have been approved entered into clinical research by targeting these genes. However, new still need be discovered. Interestingly, small nucleic acid vaccines were the market, Inclisiran, Patisiran, Inotersen, Givosiran, Lumasiran, Nusinersen, Volanesorsen, Eteplirsen, Golodirsen, Viltolarsen, Casimersen, Elasomeran, Tozinameran. agents all linear RNA agents. Circular RNAs (circRNAs) may longer half-lives, higher stability, lower immunogenicity, production costs, delivery efficiency than their covalently closed structures. CircRNA developed several companies, Orna Therapeutics, Laronde, CirCode, Therorna. studies shown that circRNAs regulate synthesis regulating ACS, YWHAG, PTEN, SREBP-2, PMK expression. MiRNAs essential circRNA-mediated biosynthesis. Notable, phase II trial inhibiting miR-122 with has completed. Suppressing circRNA_ABCA1, circ-PRKCH, circEZH2, circRNA-SCAP, circFOXO3 target development, specifically circFOXO3. This review focuses on mechanism of circRNA/miRNA axis hope providing knowledge identify targets.

Language: Английский

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Organ-Specificity of Breast Cancer Metastasis

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(21), P. 15625 - 15625

Published: Oct. 26, 2023

Breast cancer (BC) remains one of the most common malignancies among women worldwide. shows metastatic heterogeneity with priority to different organs, which leads differences in prognosis and response therapy patients. The main targets for metastasis BC are bone, lung, liver brain. molecular mechanism organ-specificity is still under investigation. In recent years, appearance new genomic approaches has led unprecedented changes understanding breast provided a platform development more effective therapeutic agents. This review summarises data on organ-specific markers as basis possible approach order improve diagnosis patients metastatically heterogeneous cancer.

Language: Английский

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EIF4A3-induced circZFAND6 promotes breast cancer proliferation and metastasis through the miR-647/FASN axis

Life Sciences, Journal Year: 2023, Volume and Issue: 324, P. 121745 - 121745

Published: April 29, 2023

Language: Английский

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CircMYBL2 facilitates hepatocellular carcinoma progression by regulating E2F1 expression

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, Journal Year: 2024, Volume and Issue: 32(6), P. 1129 - 1139

Published: Jan. 1, 2024

Circular RNAs (circRNAs) have been recognized as pivotal regulators in tumorigenesis, yet the biological functions well molecular mechanisms of majority circRNAs hepatocellular carcinoma (HCC) remain elusive.We sought to unveil expression profile and role circMYBL2 HCC.Initial microarray analyses were conducted probe HCC cells, qRT-PCR analysis was then performed cell lines tissues, revealing significant upregulation circMYBL2.Subsequent experiments evaluate function progression.Furthermore, bioinformatics analysis, luciferase reporter assays, western blot employed investigate interplay among circMYBL2, miR-1205, E2F1.CircMYBL2 found exhibit marked tumor tissues lines.Elevated increased proliferation migration whereas knockdown elicited contrasting effects.Mechanistically, our results indicated that promoted E2F1 facilitated progression by sponging miR-1205.Our findings revealed contributed through circMYBL2/miR-1205/E2F1 axis, suggesting potential a novel target for treatment or prognostic biomarker HCC.

Language: Английский

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Circ0060467 sponges miR-6805 to promote hepatocellular carcinoma progression through regulating AIFM2 and GPX4 expression

Aging, Journal Year: 2024, Volume and Issue: 16(2), P. 1796 - 1807

Published: Jan. 19, 2024

Background: Circular RNAs (circRNAs) represent a subset of non-coding implicated in the regulation diverse biological processes, including tumorigenesis. However, expression and functional implications circ0060467 hepatocellular carcinoma (HCC) remain elusive. In this study, we aimed to elucidate role modulating progression HCC. Methods: Differentially expressed circRNAs HCC tissues were identified through circRNA microarray assays. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays revealed upregulation both cell lines tissues. Various conducted investigate roles progression. Additionally, RNA immunoprecipitation (RIP) luciferase carried out assess interactions between circ0060467, microRNA-6085 (miR-6085), apoptosis-inducing factor mitochondria-associated 2 (AIFM2), glutathione peroxidase 4 (GPX4) Results: Microarray qRT-PCR analyses demonstrated marked elevation lines. Knockdown suppressed proliferation. Luciferase reporter RIP confirmed binding AIFM2, GPX4 miR-6805. Subsequent experiments that competes with AIFM2 GPX4, thereby inhibiting cancer ferroptosis by miR-6085 promoting Conclusions: Collectively, modulates levels crucial regulators tumor ferroptosis, acting as sponge for Thus, may novel diagnostic marker therapeutic target

Language: Английский

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CircTRIM1 encodes TRIM1-269aa to promote chemoresistance and metastasis of TNBC via enhancing CaM-dependent MARCKS translocation and PI3K/AKT/mTOR activation

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: May 16, 2024

Peptides and proteins encoded by noncanonical open reading frames (ORFs) of circRNAs have recently been recognized to play important roles in disease progression, but the biological functions mechanisms these peptides are largely unknown. Here, we identified a potential coding circular RNA, circTRIM1, that was upregulated doxorubicin-resistant TNBC cells intersecting transcriptome translatome RNA-seq data, its expression correlated with clinicopathological characteristics poor prognosis patients TNBC. CircTRIM1 possesses functional IRES element along an 810 nt ORF can be translated into novel endogenously expressed protein termed TRIM1-269aa. Functionally, demonstrated TRIM1-269aa, which is involved promoted chemoresistance metastasis both vitro vivo. In addition, found TRIM1-269aa packaged exosomes transmitted between cells. Mechanistically, enhanced interaction MARCKS calmodulin, thus promoting calmodulin-dependent translocation MARCKS, further initiated activation PI3K/AKT/mTOR pathway. Overall, encodes enhancing activation. Our investigation has yielded insights protein-coding supported circTRIM1/TRIM1-269aa as promising prognostic therapeutic target for

Language: Английский

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