Basal level of autophagy and <scp>MAP</scp>1<scp>LC</scp>3B‐<scp>II</scp> as potential biomarkers for <scp>DHA</scp>‐induced cytotoxicity in colorectal cancer cells

Samdal, Helle; Sandmoe, Malin Alise; Olsen, Lene Christin; Jarallah, Elaf Ali Hadi; Høiem, Therese Stork; Schønberg, Svanhild Margrethe Arentz; Pettersen, Caroline Hild

doi:10.1111/febs.14488

Cited by 9 publications

(2 citation statements)

References 55 publications

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“…The upregulation of INHBE is also a marker of the ER-stress induction in DHA-treated cells and may act on cell growth inhibition [77]. The triggering of ER-stress-induced apoptosis by DHA agrees with previous studies using colon, colorectal, and glioma cancer cells [54,[78][79][80] and even in non-alcoholic steatohepatitis patients [81]. In addition, the Glutathione-Specific Gamma-Glutamyl-cyclo-transferase encoded by the CHAC1 gene, which is also upregulated, induces a glutathione depletion that is an important factor for apoptosis initiation and execution, and thus, acts as a pro-apoptotic component of the unfolded protein response pathway by mediating the pro-apoptotic effects of the ATF4-DDIT3/CHOP cascade [82].…”

Section: Antiproliferative Effect and Induction Of Apoptosissupporting

confidence: 83%

Transcriptomic Response of Breast Cancer Cells MDA-MB-231 to Docosahexaenoic Acid: Downregulation of Lipid and Cholesterol Metabolism Genes and Upregulation of Genes of the Pro-Apoptotic ER-Stress Pathway

Chénais

Cornec

Dumont

et al. 2020

IJERPH

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Despite considerable efforts in prevention and therapy, breast cancer remains a major public health concern worldwide. Numerous studies using breast cancer cell lines have shown the antiproliferative and pro-apoptotic effects of docosahexaenoic acid (DHA). Some studies have also demonstrated the inhibitory effect of DHA on the migration and invasion of breast cancer cells, making DHA a potential anti-metastatic agent. Thus, DHA has shown its potential as a chemotherapeutic adjuvant. However, the molecular mechanisms triggering DHA effects remain unclear, and the aim of this study was to provide a transcriptomic basis for further cellular and molecular investigations. Therefore, MDA-MB-231 cells were treated with 100 µM DHA for 12 h or 24 h before RNA-seq analysis. The results show the great impact of DHA-treatment on the transcriptome, especially after 24 h of treatment. The impact of DHA is particularly visible in genes involved in the cholesterol biosynthesis pathway that is strongly downregulated, and the endoplasmic reticulum (ER)-stress response that is, conversely, upregulated. This ER-stress and unfolded protein response could explain the pro-apoptotic effect of DHA. The expression of genes related to migration and invasion (especially SERPINE1, PLAT, and MMP11) is also impacted by DHA. In conclusion, this transcriptomic analysis supports the antiproliferative, pro-apoptotic and anti-invasive effects of DHA, and provides new avenues for understanding its molecular mechanisms.

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Section: Antiproliferative Effect and Induction Of Apoptosissupporting

confidence: 83%

Transcriptomic Response of Breast Cancer Cells MDA-MB-231 to Docosahexaenoic Acid: Downregulation of Lipid and Cholesterol Metabolism Genes and Upregulation of Genes of the Pro-Apoptotic ER-Stress Pathway

Chénais

Cornec

Dumont

et al. 2020

IJERPH

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“…The omega-3 fatty acid docosahexaenoic acid (DHA) is known for having anti-cancer properties. The basal level of autophagy and MAP1LC3B protein are possible indicators for DHA sensitivity in CRC cells ( 39 ). However, the importance of TOMM22 and TOMM40 in CRC remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of mitophagy-related signatures as a novel prognostic model for colorectal cancer

Ke,

Wang,

Deng

et al. 2024

Transl Cancer Res

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Background Colorectal cancer (CRC) is one of the most commonly diagnosed cancers in the world. Mitophagy is associated with tumorigenesis and development of malignancy. However, the specific role of mitophagy has yet not been systematically explored in CRC. Methods The RNA-sequencing dataset of CRC from The Cancer Genome Atlas (TCGA) and microarray data of gene expression profiles of CRC from Gene Expression Omnibus (GEO) were downloaded. Mitophagy-related gene sets were obtained from the Pathway Unification database. The package “limma” was used for differential gene expression analysis. Kaplan-Meier (KM) survival analyses were utilized to evaluate the prognostic value of the mitophagy regulators. Single-sample gene set enrichment analysis (ssGSEA) was used to estimate the infiltrating immune cells and the activity of immune response. The ConsensusClusterPlus algorithm was used to determine mitophagy-related subtypes. Principal component analysis (PCA) was used to create composite measurement of mitophagy scores. The R packages “survminer” and “ReGlot” were used to plot the nomogram and calibration curves. Results Integrated analysis of the GEO and TCGA databases revealed some common differentially expressed genes (DEGs) in CRC. MFN2 , UBB , PINK1 , and PRKN were significantly downregulated in CRC samples as compared to normal samples, and other genes were significantly upregulated in CRC samples. KM survival analyses showed that high expression of ATG12 and MAP1LC3B predicted a poor prognosis, whereas high expression of TOMM22 and TOMM40 predicted a better prognosis. Mitophagy showed significant correlation with immune-related pathways in CRC samples. We identified 2 distinct CRC subtypes with different mitophagy accumulation, of which subtype B had better prognosis and immune activity. The mitophagy score may be employed as a new and efficient clinical predictor in conjunction with other clinical indicators to predict the prognosis of CRC patients. Conclusions We systematically investigated the CRC heterogeneity with reference to mitophagy based on bioinformatics analyses, and the findings of this study might provide some guidance for future research into potential biomarkers for diagnosis and prognosis prediction of CRC patients.

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Autophagy as a Biomarker of Cytotoxicity

Hirano

2022

Biomarkers in Toxicology

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Basal level of autophagy and MAP1LC3B‐II as potential biomarkers for DHA‐induced cytotoxicity in colorectal cancer cells

Abstract: Protocol and data for gene expression experiments have been submitted to ArrayExpress with accession number E-MTAB-5750. KeywordsAutophagy; colorectal cancer; DHA; MAP1LC3B; omega-3 Conflicts of interestThe authors report no conflicts of interest.

Cited by 9 publications

References 55 publications

Transcriptomic Response of Breast Cancer Cells MDA-MB-231 to Docosahexaenoic Acid: Downregulation of Lipid and Cholesterol Metabolism Genes and Upregulation of Genes of the Pro-Apoptotic ER-Stress Pathway

Transcriptomic Response of Breast Cancer Cells MDA-MB-231 to Docosahexaenoic Acid: Downregulation of Lipid and Cholesterol Metabolism Genes and Upregulation of Genes of the Pro-Apoptotic ER-Stress Pathway

Identification and validation of mitophagy-related signatures as a novel prognostic model for colorectal cancer

Autophagy as a Biomarker of Cytotoxicity

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