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DNMT1/miR-152-3p/SOS1 signaling axis promotes self-renewal and tumor growth of cancer stem-like cells derived from non-small cell lung cancer
- Source :
- Clinical Epigenetics, Vol 16, Iss 1, Pp 1-17 (2024)
- Publication Year :
- 2024
- Publisher :
- BMC, 2024.
-
Abstract
- Abstract Background CSLCs(Cancer stem cell-like cells), which are central to tumorigenesis, are intrinsically influenced by epigenetic modifications. This study aimed to elucidate the underlying mechanism involving the DNMT1/miR-152-3p/SOS1 axis in regulating the self-renewal and tumor growth of LCSLCs (lung cancer stem-like cells). Materials and methods Target genes of miR-152-3p were predicted using TargetScan Human 8.0. Self-renewal and tumor growth of LCSLC were compared in suspension-cultured non-small cell lung cancer (NSCLC) cell lines H460 and A549 cell-derived globe cells. Functional effects of the DNMT1/miR-152-3p/SOS1 axis were assessed through gain-of-function experiments in vitro and in vivo. Additionally, luciferase reporter assays were employed to analyze the interaction among DNMT1, miR-152-3p, and SOS1. Results Our findings highlight a negative interaction between DNMT1 and miR-152-3p, resulting in reduced miR-152-3p level. This, in turn, leads to the alleviation of the inhibitory effect of miR-152-3p on the target gene SOS1, ultimately activating SOS1 and playing an essential role in self-renewal and tumor growth of LCSLC. However, the alteration of SOS1 does not affect DNMT1/miR-152-3p regulation. Therefore, it is reasonable to infer that the DNMT1/miR-152-3p negative feedback loop critically sustains self-renewal and tumor growth of LCSLC through SOS1. Conclusions This study reveals a novel mechanism underpinning self-renewal and tumor growth of CSLC (cancer stem cell) in NSCLC and identifies potential therapeutic targets for NSCLC treatment.
Details
- Language :
- English
- ISSN :
- 18687083
- Volume :
- 16
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Clinical Epigenetics
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.fe2c3bcc913244848423e1c08c0a61a9
- Document Type :
- article
- Full Text :
- https://doi.org/10.1186/s13148-024-01663-5