Downregulation of long noncoding RNA B4GALT1-AS1 is associated with breast cancer development

ahvaz, Samaneh; Amini, Mohammad; Yari, Amirhossein; Baradaran, Behzad; Jebelli, Asiyeh; Mokhtarzadeh, Ahad

doi:10.1038/s41598-023-51124-x

Cited by 2 publications

References 40 publications

(41 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

Continuous exposure to doxorubicin induces stem cell-like characteristics and plasticity in MDA-MB-231 breast cancer cells identified with the SORE6 reporter

Salinas-Jazmín,

Medina-Mondragón,

Jiménez-López

et al. 2024

Cancer Chemother Pharmacol

View full text Add to dashboard Cite

Purpose Cancer stem cells (CSCs) account for recurrence and resistance to breast cancer drugs, rendering them a cause of mortality and therapeutic failure. In this study, we examined the effects of exposure to low concentrations of doxorubicin (Dox) on CSCs and non-CSCs from TNBC. Methods The effects of Dox were studied using the SORE6 reporter system. We examined the enrichment of the CSCs population, as well as the proliferation, and death of the reporter-positive fraction (GFP + cells) by flow cytometry. The resistant and stemness phenotypes were analyzed by viability and mammosphere formation assay, respectively. We identified differentially expressed and coregulated genes by RNA-seq analysis, and the correlation between gene expression and clinical outcome was evaluated by Kaplan-Mayer analysis using public databases. Results In MDAMB231 and Hs578t cells, we identified enriched subsets in the CSCs population after continuous exposure to low concentrations of Dox. Cells from these enriched cultures showed resistance to toxic concentrations of Dox and increased efficiency of mammosphere formation. In purified GFP + or GFP- cells, Dox increased the mammosphere-forming efficiency, promoted phenotypic switches in non-CSCs populations to a CSC-like state, reduced proliferation, and induced differential gene expression. We identified several biological processes and molecular functions that partially explain the development of doxorubicin-resistant cells and cellular plasticity. Among the genes that were regulated by Dox exposure, the expression of ITGB1, SNAI1, NOTCH4, STAT5B, RAPGEF3, LAMA2, and GNAI1 was significantly associated with poor survival, the stemness phenotype, and chemoresistance. Conclusion The generation of chemoresistant cells that have characteristics of CSCs, after exposure to low concentrations of Dox, involves the differential expression of genes that have a clinical impact.

show abstract

Continuous exposure to doxorubicin induces stem cell-like characteristics and plasticity in MDA-MB-231 breast cancer cells identified with the SORE6 reporter

Salinas-Jazmín,

Medina-Mondragón,

Jiménez-López

et al. 2024

Cancer Chemother Pharmacol

View full text Add to dashboard Cite

show abstract

CD73 restrains mutant β-catenin oncogenic activity in endometrial carcinomas

Hirsch,

Premsankar,

Kurnit

et al. 2024

Preprint

View full text Add to dashboard Cite

Missense mutations in exon 3 of CTNNB1, the gene encoding β-catenin, are associated with poor outcomes in endometrial carcinomas (EC). Clinically, CTNNB1 mutation status has been difficult to use as a predictive biomarker as β-catenin oncogenic activity is modified by other factors, and these determinants are unknown. Here we reveal that CD73 restrains the oncogenic activity of exon 3 β-catenin mutants, and its loss associates with recurrence. Using 7 patient-specific mutants, with genetic deletion or ectopic expression of CD73, we show that CD73 loss increases β-catenin-TCF/LEF transcriptional activity. In cells lacking CD73, membrane levels of mutant β-catenin decreased which corresponded with increased levels of nuclear and chromatin-bound mutant β-catenin. These results suggest CD73 sequesters mutant β-catenin to the membrane to limit its oncogenic activity. Adenosine A1 receptor deletion phenocopied increased β-catenin-TCF/LEF activity seen with NT5E deletion, suggesting that the effect of CD73 loss on mutant β-catenin is mediated via attenuation of adenosine receptor signaling. RNA-seq analyses revealed that NT5E deletion alone drives pro-tumor Wnt/β-catenin gene expression and, with CD73 loss, β-catenin mutants dysregulate zinc-finger and non-coding RNA gene expression. We identify CD73 as a novel regulator of oncogenic β-catenin and help explain variability in patient outcomes in CTNNB1 mutant EC.

show abstract

Downregulation of long noncoding RNA B4GALT1-AS1 is associated with breast cancer development

Cited by 2 publications

References 40 publications

Continuous exposure to doxorubicin induces stem cell-like characteristics and plasticity in MDA-MB-231 breast cancer cells identified with the SORE6 reporter

Continuous exposure to doxorubicin induces stem cell-like characteristics and plasticity in MDA-MB-231 breast cancer cells identified with the SORE6 reporter

CD73 restrains mutant β-catenin oncogenic activity in endometrial carcinomas

Contact Info

Product

Resources

About