Targeting multiple genes containing long mononucleotide A-T repeats in lung cancer stem cells

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dc.contributor.authorBhummaphan, Narumol
dc.contributor.authorPin-on, Piyapat
dc.contributor.authorPhiboonchaiyanan, Preeyaporn Plaimee
dc.contributor.authorSiriluksana, Jirattha
dc.contributor.authorAporntewan, Chatchawit
dc.contributor.authorChanvorachote, Pithi
dc.contributor.authorMutirangura, Apiwat
dc.date.accessioned2026-08-06T10:34:11Z
dc.date.available2026-08-06T10:34:11Z
dc.date.issued2021-12-01
dc.description.abstractBackground: Intratumour heterogeneous gene expression among cancer and cancer stem cells (CSCs) can cause failure of current targeted therapies because each drug aims to target the function of a single gene. Long mononucleotide A-T repeats are cis-regulatory transcriptional elements that control many genes, increasing the expression of numerous genes in various cancers, including lung cancer. Therefore, targeting A-T repeats may dysregulate many genes driving cancer development. Here, we tested a peptide nucleic acid (PNA) oligo containing a long A-repeat sequence [A(15)] to disrupt the transcriptional control of the A-T repeat in lung cancer and CSCs. Methods: First, we separated CSCs from parental lung cancer cell lines. Then, we evaluated the role of A-T repeat gene regulation by counting the number of repeats in differentially regulated genes between CSCs and the parental cells of the CSCs. After testing the dosage and effect of PNA-A15 on normal and cancer cell toxicity and CSC phenotypes, we analysed genome-wide expression to identify dysregulated genes in CSCs. Results: The number of A-T repeats in genes differentially regulated between CSCs and parental cells differed. PNA-A15 was toxic to lung cancer cells and CSCs but not to noncancer cells. Finally, PNA-A15 dysregulated a number of genes in lung CSCs. Conclusion: PNA-A15 is a promising novel targeted therapy agent that targets the transcriptional control activity of multiple genes in lung CSCs.
dc.identifier.citationJournal of Translational Medicine, 19(1), 2021
dc.identifier.doi10.1186/s12967-021-02902-6
dc.identifier.issn14795876
dc.identifier.other2-s2.0-85107357237
dc.identifier.urihttps://dspace.kmitl.ac.th/handle/123456789/12448
dc.sourceJournal of Translational Medicine
dc.subjectCancer stem cells
dc.subjectHallmark of cancer
dc.subjectLung cancer
dc.subjectMononucleotide A-T repeats
dc.subjectUniversal target
dc.titleTargeting multiple genes containing long mononucleotide A-T repeats in lung cancer stem cells
dc.typeArticle

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