FTO-mediated LINC01134 stabilization to promote chemoresistance through miR-140-3p/WNT5A/WNT pathway in PDAC DOI Creative Commons
Lu Jin, Yongsheng Yang, Xiangliang Liu

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(11)

Published: Nov. 1, 2023

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer most frequently detected at an advanced stage that limits treatment options to systemic chemotherapy, which has provided only marginal positive clinical outcomes. Currently, the first-line chemotherapeutic agent for PDAC gemcitabine (GEM). However, chemotherapy resistance GEM often overlooked in of due lack effective biological markers. Therefore, it crucial find new prognostic markers and therapeutic targets patients with PDAC. In this study, we identified novel regulatory mechanism development Here, report LINC01134 was significantly upregulated primary tumors from patients. vitro vivo functional studies revealed promotes through facilitating stem cell features modulating cycle. Mechanistically, interactes tumor suppressor miR-497-5p cells. Increased downregulates miR-140-3p oncogenic WNT5A expression. Moreover, m 6 A demethylase FTO participated upregulation by maintaining mRNA stability YTHDF2. Taken together, present study suggested FTO-mediated stabilization promote miR-140-3p/WNT5A/WNT pathway Our

Language: Английский

Targeting epigenetic regulators to overcome drug resistance in cancers DOI Creative Commons
Nan Wang, Ting Ma, Bin Yu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Feb. 17, 2023

Abstract Drug resistance is mainly responsible for cancer recurrence and poor prognosis. Epigenetic regulation a heritable change in gene expressions independent of nucleotide sequence changes. As the common epigenetic mechanisms, DNA methylation, histone modification, non-coding RNA have been well studied. Increasing evidence has shown that aberrant regulations contribute to tumor resistance. Therefore, targeting regulators represents an effective strategy reverse drug In this review, we summarize roles addition, as essential factors modifications, demethylases mediate or genomic modifications. Herein, comprehensively describe functions demethylase family including lysine-specific family, Jumonji C-domain-containing arginine fully discuss their regulatory mechanisms related therapeutic strategies, small-molecule inhibitors small interfering overcome resistance, are also described.

Language: Английский

Citations

159
Loss of lncRNA LINC01056 leads to sorafenib resistance in HCC DOI Creative Commons

Yau-Tuen Chan,

Junyu Wu, Yuanjun Lu

et al.

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

Published: April 6, 2024

Abstract Background and aims Sorafenib is a major nonsurgical option for patients with advanced hepatocellular carcinoma (HCC); however, its clinical efficacy largely undermined by the acquisition of resistance. The aim this study was to identify key lncRNA involved in regulation sorafenib response HCC. Materials methods A clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) single-guide RNA (sgRNA) synergistic activation mediator (SAM)-pooled library applied screen regulated treatment. role identified mediating HCC examined vitro vivo. underlying mechanism delineated proteomic analysis. significance expression evaluated multiplex immunostaining on human microtissue array. Results CRISPR/Cas9 screening revealed that Linc01056 among most downregulated lncRNAs sorafenib-resistant cells. Knockdown reduced sensitivity cells sorafenib, suppressing apoptosis promoting tumour growth mice Proteomic analysis knockdown sorafenib-treated induced genes related fatty acid oxidation (FAO) while repressing glycolysis-associated genes, leading metabolic switch favouring higher intracellular energy production. FAO inhibition significantly restored sorafenib. Mechanistically, we determined PPARα critical molecule governing upon indeed, tumours Clinically, predicted optimal overall progression-free survival outcomes better response. indicated low level Conclusion Our as epigenetic regulator potential therapeutic target

Language: Английский

Citations

22
Histone lactylation promotes multidrug resistance in hepatocellular carcinoma by forming a positive feedback loop with PTEN DOI Creative Commons
Yuan Zeng, Haoran Jiang, Zhoufeng Chen

et al.

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 31, 2025

Language: Английский

Citations

4
Histone lactylation drives liver cancer metastasis by facilitating NSF1-mediated ferroptosis resistance after microwave ablation DOI Creative Commons
Jiayan Huang, Huijing Xie,

Ju Li

et al.

Redox Biology, Journal Year: 2025, Volume and Issue: 81, P. 103553 - 103553

Published: Feb. 15, 2025

Language: Английский

Citations

2
Long noncoding RNA TLNC1 promotes the growth and metastasis of liver cancer via inhibition of p53 signaling DOI Creative Commons
Kefei Yuan,

Jiang Lan,

Lin Xu

et al.

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

Published: April 27, 2022

Long non-coding RNAs (lncRNAs) have been demonstrated to play vital roles in cancer development and progression. However, their biological function mechanisms liver remain largely unknown.RNA-seq was performed with clinical hepatoma tissues paired adjacent normal identify differentially expressed lncRNAs. qPCR utilized examine the expression levels of We studied TLNC1 cell growth metastasis both mouse models. RNA-seq, RNA pull-down coupled mass spectrometry, immunoprecipitation, dual luciferase reporter assay, surface plasmon resonance analysis were used analyze functional mechanism TLNC1.Based on intersection our own TCGA survival data, identified as a potential tumorigenic lncRNA cancer. significantly enhanced cells vitro vivo. exerted its through interaction TPR inducing TPR-mediated transportation p53 from nucleus cytoplasm, thus repressing transcription target genes finally contributing progression cancer.TLNC1 is promising prognostic factor cancer, TLNC1-TPR-p53 axis can serve therapeutic for treatment.

Language: Английский

Citations

63
RNA-binding protein ZCCHC4 promotes human cancer chemoresistance by disrupting DNA-damage-induced apoptosis DOI Creative Commons
Ha Zhu, Kun Chen,

Yali Chen

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: July 20, 2022

RNA-binding proteins (RBPs) play important roles in cancer development and treatment. However, the tumor-promoting RBPs their partners, which may potentially serve as therapeutic targets, need to be further identified. Here, we report that zinc finger CCHC domain-containing protein 4 (ZCCHC4) is of aberrantly high expression multiple human tissues associated with poor prognosis chemoresistance patients hepatocellular carcinoma (HCC), pancreatic colon cancer. ZCCHC4 promotes HCC cells DNA-damage agent (DDA) both vitro vivo. cell deficiency reduces tumor growth vivo intratumoral interference obviously enhances DDA-induced antitumor effect. Mechanistically, inhibits DNA-damage-induced apoptosis by interacting a new long noncoding RNA (lncRNA) AL133467.2 hamper its pro-apoptotic function. Also, blocks interaction between γH2AX upon DDA treatment inhibit apoptotic signaling promote DDAs. Knockout for enhancing chemosensitivity cells. Together, our study identifies predictor potential target improving chemotherapy effects, providing mechanistic insights partners progression chemoresistance.

Language: Английский

Citations

51
CAF-derived exosomal lncRNA FAL1 promotes chemoresistance to oxaliplatin by regulating autophagy in colorectal cancer DOI

Sixian Zhu,

Jie Mao, Xiaoli Zhang

et al.

Digestive and Liver Disease, Journal Year: 2023, Volume and Issue: 56(2), P. 330 - 342

Published: July 1, 2023

Language: Английский

Citations

28
Mitochondrial-related drug resistance lncRNAs as prognostic biomarkers in laryngeal squamous cell carcinoma DOI Creative Commons
Zhimin Wu, Yi Chen,

Dizhi Jiang

et al.

Discover Oncology, Journal Year: 2024, Volume and Issue: 15(1)

Published: Dec. 18, 2024

Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor of the head and neck that significantly impacts patients' quality life, with chemotherapy resistance notably affecting prognosis. This study aims to identify prognostic biomarkers optimize treatment strategies for LSCC. Using data from The Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO), combined mitochondrial gene database analysis, we identified lncRNAs associated drug genes. Key long non-coding RNAs (lncRNAs) were selected through univariate Cox regression Lasso regression, multivariate model was constructed predict We further analyzed differences in immune function biological pathway enrichment between high- low-risk groups, developed nomogram, compared sensitivity. Results showed based on seven could serve as an independent factor, Area Under Curve (AUC) values 0.746, 0.827, 0.771 at 1, 3, 5 years, respectively, outperforming some existing models, demonstrating high predictive performance. Significant observed sensitivity groups. risk prediction incorporating resistance-related can accurately independently prognosis LSCC patients.

Language: Английский

Citations

10
AURKB inhibition induces rhabdomyosarcoma apoptosis and ferroptosis through NPM1/SP1/ACSL5 axis DOI Creative Commons

Huimou Chen,

Mengzhen Li, Yu Zhang

et al.

JCI Insight, Journal Year: 2025, Volume and Issue: 10(3)

Published: Feb. 10, 2025

Rhabdomyosarcoma (RMS) is one of the most common solid tumors in children and adolescents. Patients with relapsed/refractory RMS have limited treatment options, highlighting urgency for identification novel therapeutic targets RMS. In present study, aurora kinase B (AURKB) was found to be highly expressed associated unfavorable prognosis patients. Functional experiments indicated that inhibition AURKB significantly reduced cell proliferation, induced apoptosis ferroptosis, suppressed growth vivo. The contributes ferroptosis resistance tumor cells through nucleophosmin 1 (NPM1)/Sp1 transcription factor (SP1)/acyl-CoA synthetase long-chain family member 5 (ACSL5) axis. Furthermore, exerted an anti-RMS effect together vincristine both vitro vivo, tolerable toxicity. above findings provide insights we believe are new into tumorigenesis RMS, especially regard or resistance, indicating may a potential target clinical intervention patients

Language: Английский

Citations

1
Leveraging non-enzymatic functions of LSD1 for novel therapeutics DOI
Yihui Song, Bin Yu

Trends in Pharmacological Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

1