miR‐135b: A Potential Biomarker for Pathological Diagnosis and Biological Therapy

Wiley Interdisciplinary Reviews - RNA, Journal Year: 2025, Volume and Issue: 16(2)

Published: March 1, 2025

ABSTRACT MicroRNAs (miRNAs) are a class of endogenous non‐coding RNAs found in eukaryotes with post‐transcriptional regulatory functions. A variety miRNAs is differentially expressed cancer tissues and thus can be used as biomarkers. microRNA‐135b‐5p (miR‐135b) has been shown to involved the pathological processes neoplastic non‐neoplastic diseases. Under different conditions, miR‐135b tumor suppressive carcinogenic effects. regulates development cancer, including metabolism, proliferation, apoptosis, invasion, fibrosis, angiogenesis, immunomodulation, drug resistance. new biomarker for diagnosis prognosis, which potential clinical guidance. This article reviews relevant research on miR‐135B field tumors, biogenesis background miR‐135b, expression related targets signaling pathways mediating progression order sort out explore transformation value miR‐135b.

Language: Английский

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Disease‐Associated Risk Variants and Expression Levels of the lncRNA, CDKN2B‐AS1, Are Associated With the Progression of HCC

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(6)

Published: March 1, 2025

ABSTRACT The most susceptible loci of hepatocellular carcinoma (HCC) identified by genome‐wide association studies are located in non‐coding regions. antisense RNA at the INK4 locus (ANRIL), also known as cyclin‐dependent kinase inhibitor 2B 1 (CDKN2B‐AS1), is a long (lnc)RNA situated within and to genes encoding CDKN2A/B on chromosome 9p21.3. Single‐nucleotide polymorphisms (SNPs) CDKN2B‐AS1 associated with several cancer types, but their impacts HCC remain unclear. In this study, we investigated effects SNPs both susceptibility its clinicopathological development. Five SNP loci—rs564398 (T/C), rs1333048 (A/C), rs1537373 (G/T), rs2151280 (A/G) rs8181047 (G/A)—were analysed using TaqMan allelic discrimination assay for genotyping cohort 810 patients 1190 healthy controls. Under dominant model, least one minor C‐allele rs564398 showed lower risk liver cirrhosis (odds ratio (OR) = 0.677). Additionally, GT + TT genotype had reduced developing large tumours (T3 T4) advanced clinical stages (III/IV), particularly male population (OR 0.644 0.679). Furthermore, data from Cancer Genome Atlas revealed that expression levels were elevated tissues compared normal correlated T stages, high histological grades poor prognoses. Our findings suggest polymorphic variants may influence development progression Taiwanese population.

Language: Английский

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COPS5 Triggers Ferroptosis Defense by Stabilizing MK2 in Hepatocellular Carcinoma

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 8, 2025

Abstract Sorafenib, which is proven to serve as a potent ferroptosis inducer, used first‐line treatment for patients with advanced hepatocellular carcinoma (HCC), but it has limited clinical benefits, mainly due drug resistance. Herein, using genome‐wide CRISPR/Cas9 knockout screening and multiple functional studies, this work identifies COP9 signalosome subunit 5 (COPS5) driver of sorafenib resistance suppressor in HCC. Consistently, the amplification overexpression COPS5 are frequently observed HCC samples, associated poor patient prognosis might predict response therapy. Mechanistically, stabilized mitogen‐activated protein kinase 2 (MK2) through deubiquitination and, turn, induced activation heat shock beta‐1 (HSPB1), repressor, thereby protecting cells from consequently leading tumor progression, while its own expression could be by via activating transcription factor 4 (ATF4)‐activated transcription. Furthermore, pharmacological inhibition COPS5/MK2 synergize induce suppress progression. This data reveals crucial role triggering defense MK2‐HSPB1 axis highlights potential targeting combined promising strategy treating

Language: Английский

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miR-1225-3p regulates fibrosis in mesangial cells via SMURF2-mediated ubiquitination of ChREBP in diabetic kidney disease

Renal Failure, Journal Year: 2025, Volume and Issue: 47(1)

Published: April 11, 2025

Diabetic kidney disease (DKD), characterized by mesangial fibrosis and renal dysfunction, is a major microvascular complication of diabetes. Studies have shown that miRNAs are closely related to the progression DKD. Therefore, in this study, we aimed explore whether miR-1225-3p can regulate Smad ubiquitin regulatory factor 2 (SMURF2)-mediated carbohydrate response element binding protein (ChREBP) ubiquitination through Rho GTPase-activating 5 (ARHGAP5) affect DKD mice were established intraperitoneally injecting streptozocin (STZ), cell model was generated culturing media supplemented with 25 mmol/L glucose (high glucose, HG). StarBase used predict target sites between ARHGAP5, dual-luciferase reporter gene assay verify relationship. Western blotting, RT-qPCR, flow cytometry, immunoprecipitation, ELISAs, HE staining, Masson staining detect relevant indicators. ARHGAP5 SMURF2 expression decreased, but ChREBP highly expressed tissue HG-induced mouse cells (MMCs). could transcription an association revealed. facilitated oxidative stress MCCs inhibiting ARHGAP5. In addition, promoted HA-ChREBP, mediating ARHGAP5/SMURF2-mediated MCCs. Furthermore, inhibitor inhibited inflammation tissues mice. facilitates ChREBP.

Language: Английский

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NEIL3 Deficiency Enhances HCC Cell Sensitivity to Oxaliplatin by Inhibiting the Fanconi Anaemia Pathway

Cell Biology International, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

ABSTRACT Despite some achievements in oxaliplatin‐based chemotherapy for the treatment of advanced hepatocellular carcinoma (HCC), abnormal activation DNA damage repair pathways HCC cells remains a major problem, limiting efficacy chemotherapy. In previous study, we found that endonuclease VIII‐like protein 3 (NEIL3) is expressed high proportion patients with and associated an unfavourable prognosis. However, role NEIL3 chemoresistance still unclear. The aim this study was to evaluate whether how regulates oxaliplatin anti‐tumour efficacy. Gene expression after cell lines assessed by real‐time quantitative PCR, western blot analysis bioinformatics analysis. effect on regulating using counting kit‐8 assays, colony formation flow cytometry vivo nude mice study. Mechanistic insights into sensitivity mediated inhibition were obtained through immunofluorescence RNA sequencing analyses. Our findings demonstrated markedly downregulated administration. knockdown impaired viability increased apoptosis exposed oxaliplatin. addition, reduced tumour progression enhanced xenograft models. Furthermore, knocking down significantly oxaliplatin‐mediated Fanconi anaemia pathway. results revealed may be promising therapeutic target improving HCC.

Language: Английский

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circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Sept. 24, 2024

Recent evidence has demonstrated that abnormal expression and regulation of circular RNA (circRNAs) are implicated in the development progression various tumors. The aim this study was to investigate effects circ_SMA4 Gastrointestinal Stromal Tumors (GISTs) malignant progression. Human circRNAs microarray analysis conducted identify differentially expressed (DE) GISTs. effect on cell proliferation, invasion, migration, apoptosis assessed both vitro vivo settings. Dual-luciferase reporter assay, RT-qPCR, Western-blot, rescue assay were employed confirm interaction between circ_SMA4/miR-494-3p/ KIT axis. results revealed significantly upregulated GISTs, exhibited high diagnostic efficiency with an AUC 0.9824 (P < 0.01). promoted while inhibiting GISTs cells, vivo. Silencing partially inhibited Additionally, acted as a competing endogenous (ceRNA) by targeting miR-494-3p, identified functional gene for miR-494-3p Furthermore, confirmed axis plays role activating JAK/STAT signaling pathway Therefore, first time, we have emphasized is oncogenic sponging activate KIT/JAK/STAT pathway. These findings underscore may serve novel biomarker therapeutic target

Language: Английский

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WTAP‐mediated m6A modification of circ_0032463 promotes osteosarcoma progression by sponging miR‐145‐5p and regulating GFRA1 expression

Journal of Biochemical and Molecular Toxicology, Journal Year: 2024, Volume and Issue: 38(9)

Published: Sept. 1, 2024

Osteosarcoma (OS) is the most frequent bone malignancy in humans. Previous evidence suggest that circ_0032463 an oncogenic circular RNA (circRNA) various cancers, including OS. However, molecular mechanism of involved OS still unclear. Circ_0032463, microRNA-145-5p (miR-145-5p), GDNF receptor alpha 1 (GFRA1), and Wilms tumor 1-associated protein (WTAP) levels were determined using real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, apoptosis, migration, invasion, angiogenesis analyzed 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell, tube formation assays. Western blot analysis was performed to measure matrix metalloproteinase 2 (MMP2), MMP9, GFRA1, WTAP levels. Binding between miR-145-5p or GFRA1 confirmed a dual-luciferase reporter pull-down assay. The biological role on cell growth also xenograft model vivo. Methylated immunoprecipitation assay validated interaction circ_0032463. increased, decreased tissues cells. Circ_0032463 deficiency might hinder angiogenesis, promote apoptosis vitro. Mechanically, worked as sponge increase expression. Repression knockdown proved Besides, N6-methyladenosine (m6A) modification facilitates biogenesis Taken together, m6A-mediated malignant behavior partly via regulating miR-145-5p/GFRA1 axis, suggesting promising marker for treatment.

Language: Английский

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Hsa_circ_0048764 facilitates the progression of non-small cell lung cancer by targeting miR-1178-3p/HMGA1 axis

Cellular Signalling, Journal Year: 2024, Volume and Issue: unknown, P. 111484 - 111484

Published: Oct. 1, 2024

Language: Английский

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Human umbilical cord mesenchymal stem cells small extracellular vesicles-derived miR-370-3p inhibits cervical precancerous lesions by targeting DHCR24

Stem Cells Translational Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 26, 2024

Abstract Background Cervical cancer is often caused by persistent high-risk human papillomavirus (HPV) infection, causing precancerous lesions. Human umbilical cord mesenchymal stem cells-derived small extracellular vesicles (hucMSC-sEV) exhibit diverse effects on tumors. This study investigates hucMSC-sEV, the impact and mechanisms HPV-positive cervical lesion cells to provide new treatment insights. Materials Methods We previously obtained hucMSC hucMSC-sEV. In vitro experiments evaluated hucMSC-sEV proliferation migration of S12 (derived from lesions). Bioinformatics identified key microRNA components, their cell was investigated. The target gene component predicted confirmed via bioinformatics dual-luciferase reporter assays. Lentiviral systems overexpressed in examine impacts. SH-42 inhibitor used investigate potential. Immunohistochemistry assessed expression lesions tissue. Results significantly inhibited migration. miR-370-3p as an effective cargo, which also suppressed targeting DHCR24 (24-Dehydrocholesterol Reductase). overexpression reversed miR-370-3p’s inhibitory effects, while counteracted overexpression’s promoting effects. Clinical specimen analysis supported these findings, demonstrating a positive correlation between protein lesions’ progression. Conclusions inhibits migration, mediated regulate cellular cholesterol content. inhibition reduces level functions, suggesting its potential therapeutic

Language: Английский

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Arenobufagin Induces Ferroptosis in Glioblastoma Cells via Modulating the MiR‐149‐5p/AEBP1 Axis

Journal of Applied Toxicology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

ABSTRACT Accumulating evidences have proved Arenobufagin (ArBu) exhibited cytotoxic effects to multiple types of cancer. However, in glwioblastoma (GBM), which is easy develop resistance classic chemotherapy reagent, the therapeutic ArBu not been explored. In current study, we found that GBM cells were sensitive treatment and induced cell death both a dose‐dependent time‐dependent manner. was observed promote ROS accumulating elevate Fe 2+ /MDA/GSH level, lead ferroptosis. Mechanistically, significantly downregulated AEBP1 expression decreased mRNA stability without affecting its transcription. Then, predicted bind with miR‐149‐5p cells, directly target 3′UTR. At last, could upregulate suppress expression, rescue experiments confirmed miR‐149‐5p/AEBP1 axis regulated ferroptosis, underlay cells. This study revealed ferroptosis manner via modulating axis. It provides for clinical application GBM.

Language: Английский

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