Cetuximab promotes RSL3-induced ferroptosis by suppressing the Nrf2/HO-1 signalling pathway in KRAS mutant colorectal cancer

Cell Death and Disease, Год журнала: 2021, Номер 12(11)

Опубликована: Ноя. 13, 2021

Abstract Cetuximab is approved for the treatment of metastatic colorectal cancer (mCRC) with RAS wild-type. Nevertheless, prognosis remains poor and effectiveness cetuximab limited in KRAS mutant mCRC. Recently, emerging evidence has shown that ferroptosis, a newly discovered form nonapoptotic cell death, closely related to cells. Here, we further investigated whether cetuximab-mediated regulation p38/Nrf2/HO-1 promotes RSL3-induced ferroptosis plays pivotal role overcoming drug resistance (CRC). In our research, used two CRC lines, HCT116 DLD-1, as models intrinsic cetuximab. The viability cells treated combination RSL3 was assessed by CCK-8 colony formation assays. effective promote evaluating lipid reactive oxygen species accumulation expression malondialdehyde intracellular iron assay. therapy contributed regulating axis, determined western blotting transfection small interfering RNAs. promoted inhibiting Nrf2/HO-1 cells, this demonstrated xenograft nude mouse model. Our work reveals enhances cytotoxic effect on axis through activation p38 MAPK.

Язык: Английский

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Role of Epithelial to Mesenchymal Transition in Colorectal Cancer

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(19), С. 14815 - 14815

Опубликована: Окт. 1, 2023

The epithelial–mesenchymal transition (EMT) is a cellular reprogramming process that occurs during embryonic development and adult tissue homeostasis. This involves epithelial cells acquiring mesenchymal phenotype. Through EMT, cancer acquire properties associated with more aggressive EMT its opposite, mesenchymal–epithelial (MET), have been described in tumors over the past ten years, including colorectal (CRC). When activated, expression of marker E-cadherin decreased vimentin raised. As result, temporarily take on phenotype, becoming motile promoting spread tumor cells. Epithelial–mesenchymal plasticity (EMP) has become hot issue CRC because strong inducers (such as transforming growth factor β, TGF-β) can initiate regulate metastasis, microenvironment, immune system resistance CRC. In this review, we into account significance EMT-MET impact cells’ prognosis analysis connection between stem (CCSCs) will help to further clarify current meager understandings EMT. Recent advances affecting important transcription factors CCSCs are highlighted. We come conclusion regulatory network for complicated, great deal crosstalk alternate paths. More thorough research required effectively connect clinical management biomarkers targeted treatments

Язык: Английский

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The m6A modification mediated-lncRNA POU6F2-AS1 reprograms fatty acid metabolism and facilitates the growth of colorectal cancer via upregulation of FASN

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Март 16, 2024

Abstract Background Long noncoding RNAs (lncRNAs) have emerged as key players in tumorigenesis and tumour progression. However, the biological functions potential mechanisms of lncRNAs colorectal cancer (CRC) are unclear. Methods The novel lncRNA POU6F2-AS1 was identified through bioinformatics analysis, its expression CRC patients verified via qRT–PCR FISH. In vitro vivo experiments, such BODIPY staining, Oil Red O triglyceride (TAG) assays, liquid chromatography mass spectrometry (LC-MS) were subsequently performed with specimens cells to determine clinical significance, functional roles POU6F2-AS1. Biotinylated RNA pull-down, RIP, Me-RIP, ChIP, patient-derived organoid (PDO) culture assays confirm underlying mechanism Results is markedly upregulated associated adverse clinicopathological features poor overall survival patients. Functionally, promotes growth lipogenesis both vivo. Mechanistically, METTL3-induced m 6 A modification involved upregulation Furthermore, could tether YBX1 FASN promoter induce transcriptional activation, thus facilitating cells. Conclusions Our data revealed that plays a critical role fatty acid metabolism might provide promising biomarker therapeutic target for CRC.

Язык: Английский

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Exploring the integration of nanotechnology in the development and application of biosensors for enhanced detection and monitoring of colorectal cancer

Inorganic Chemistry Communications, Год журнала: 2024, Номер 164, С. 112409 - 112409

Опубликована: Апрель 12, 2024

Язык: Английский

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Artificial Intelligence Applications in the Treatment of Colorectal Cancer: A Narrative Review

Clinical Medicine Insights Oncology, Год журнала: 2024, Номер 18

Опубликована: Янв. 1, 2024

Colorectal cancer is the third most prevalent worldwide, and its treatment has been a demanding clinical problem. Beyond traditional surgical therapy chemotherapy, newly revealed molecular mechanisms diversify therapeutic approaches for colorectal cancer. However, selection of personalized among multiple options become another challenge in era precision medicine. Artificial intelligence recently increasingly investigated This narrative review mainly discusses applications artificial patients. A comprehensive literature search was conducted MEDLINE, EMBASE, Web Science to identify relevant papers, resulting 49 articles being included. The results showed that, based on different categories data, can predict outcomes essential guidance information novel therapies, thus enabling individualized strategy Some frequently implemented machine learning algorithms deep frameworks have also employed long-term prognosis prediction patients with Overall, shows encouraging evaluation

Язык: Английский

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An automated deep learning pipeline for EMVI classification and response prediction of rectal cancer using baseline MRI: a multi-centre study

npj Precision Oncology, Год журнала: 2024, Номер 8(1)

Опубликована: Янв. 22, 2024

ABSTRACT The classification of extramural vascular invasion status using baseline magnetic resonance imaging in rectal cancer has gained significant attention as it is an important prognostic marker. Also, the accurate prediction patients achieving complete response with primary staging MRI assists clinicians determining subsequent treatment plans. Most studies utilised radiomics-based methods, requiring manually annotated segmentation and handcrafted features, which tend to generalise poorly. We retrospectively collected 509 from 9 centres, proposed a fully automated pipeline for EMVI CR diffusion weighted T2-weighted imaging. applied nnUNet, self-configuring deep learning model, tumour employed learned multiple-level image features train models, named MLNet. This ensures more comprehensive representation terms both fine-grained detail global context. On external validation, MLNet, yielding similar AUCs internal outperformed 3D ResNet10, neural network ten layers designed analysing spatiotemporal data, tasks. For prediction, MLNet showed better results than current state-of-the-art model clinical same cohort. Our study demonstrated that incorporating multi-level representations by based on improves good generalisation data. observed variations contributions individual feature maps different potential be settings, particularly classification.

Язык: Английский

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Targeting ACAT1 in cancer: from threat to treatment

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Апрель 24, 2024

Altered cholesterol metabolism has been identified as a critical feature of cancers. Cholesterol functions the main component cell membrane, and is required for sustaining membrane integrity mediating signaling transduction survival. The intracellular level dynamically regulated. Excessive could be converted to less toxic cholesteryl esters by acyl-coenzyme A:cholesterol acyltransferases (ACATs). While ACAT2 limited value in cancers, ACAT1 found widely participated tumor initiation progression. Moreover, due important role immune function, also essential regulating anti-tumor immunity. inhibition may exploited potential strategy enhance immunity eliminate tumors. Herein, comprehensive understanding development provide new insights strategies.

Язык: Английский

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Checkpoint kinase 1 in colorectal cancer: Upregulation of expression and promotion of cell proliferation

World Journal of Clinical Oncology, Год журнала: 2025, Номер 16(3)

Опубликована: Янв. 20, 2025

BACKGROUND Colorectal cancer (CRC) is a prevalent malignant tumor characterized by high mortality rate, with significant challenges persisting in the identification and management of its metastatic stage. The role checkpoint kinase 1 (CHEK1), cell cycle kinase, CRC has not been fully clarified. We hypothesize that upregulation CHEK1 may enhance proliferation cells, indicating potential as novel therapeutic target for therapy. AIM To investigate expression function CRC, this study utilizes single-cell RNA sequencing tissue microarray data. METHODS Single-cell technology was employed to analyze cells from GSE144735 dataset, immunohistochemistry conducted confirm adjacent tissues. also integrated mRNA data multiple public databases assess global CRC. Molecular docking experiments were performed explore interaction between drug nitidine chloride (NC), well influence on proliferation. RESULTS found comparatively elevated epithelial marked levels Immunohistochemical analysis further confirmed tissues, receiver operating characteristic curve demonstrated accuracy (area under = 0.964) biomarker. Analysis datasets indicated statistically overexpression (standard mean difference 1.81, P < 0.01), summary yielding sensitivity specificity values 0.83 0.88, respectively. studies NC specifically targeted CHEK1, while clustered regularly interspaced short palindromic repeats knockout promoted CONCLUSION Upregulation promotes However, dataset's diversity limited, requiring investigation into specific mechanisms.

Язык: Английский

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AP4 suppresses DNA damage, chromosomal instability and senescence via inducing MDC1/Mediator of DNA damage Checkpoint 1 and repressing MIR22HG/miR-22-3p

Molecular Cancer, Год журнала: 2022, Номер 21(1)

Опубликована: Май 27, 2022

AP4 (TFAP4) encodes a basic helix-loop-helix leucine zipper (bHLH-LZ) transcription factor and is direct target gene of the oncogenic c-MYC. Here, we set out to determine relevance in human colorectal cancer (CRC) cells.A CRISPR/Cas9 approach was employed generate AP4-deficient CRC cell lines with inducible expression Colony formation, β-gal staining, immunofluorescence, comet homologous recombination (HR) assays RNA-Seq analysis were used effects inactivation. qPCR qChIP analyses performed validate differentially expressed targets. Expression data from cohorts subjected bioinformatics analyses. Immunohistochemistry evaluate targets vivo. Ap4-deficient APCmin/+ mice analyzed conservation. Immunofluorescence, chromosome micronuclei enumeration, MTT colony formation inactivation regulation on chromosomal instability (CIN) drug sensitivity.Inactivation resulted increased spontaneous c-MYC-induced DNA damage, cellular senescence. cells displayed long non-coding RNA MIR22HG, which miR-22-3p directly repressed by AP4. Furthermore, Mediator damage Checkpoint 1 (MDC1), central component response known miR-22-3p, decreased cells. Accordingly, MDC1 induced indirectly AP4-mediated repression miR-22-3p. Adenomas organoids conservation these regulations. Inhibition or ectopic reversed senescence, CIN defective HR observed AP4-deficiency also sensitized 5-FU treatment, whereas conferred resistance MDC1-dependent manner.In summary, AP4, form conserved coherent, regulatory feed-forward loop promote repair, suppresses senescence CIN, contributes resistance. These findings explain how elevated development chemo-resistance after c-MYC activation.

Язык: Английский

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Understanding the role of DNA methylation in colorectal cancer: Mechanisms, detection, and clinical significance

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2024, Номер 1879(3), С. 189096 - 189096

Опубликована: Март 17, 2024

Язык: Английский

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