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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.
Yuan, Qing; Wang, Rubo; Li, Xiang; Sun, Fei; Lin, Jiazhi; Fu, Zhimin; Zhang, Jiansong.
Afiliación
  • Yuan Q; Department of Preclinical Medicine, Medical College, Hunan Normal University, Changsha, 410013, China.
  • Wang R; Key Laboratory of Study and Discover of Small Targeted Molecules of Hunan Province, Changsha, 410013, China.
  • Li X; Department of Pathology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China.
  • Sun F; Department of Preclinical Medicine, Medical College, Hunan Normal University, Changsha, 410013, China.
  • Lin J; Key Laboratory of Study and Discover of Small Targeted Molecules of Hunan Province, Changsha, 410013, China.
  • Fu Z; Department of Preclinical Medicine, Medical College, Hunan Normal University, Changsha, 410013, China.
  • Zhang J; Key Laboratory of Study and Discover of Small Targeted Molecules of Hunan Province, Changsha, 410013, China.
Clin Epigenetics ; 16(1): 55, 2024 Apr 15.
Article en En | MEDLINE | ID: mdl-38622665
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / MicroARNs / Neoplasias Pulmonares Límite: Humans Idioma: En Revista: Clin Epigenetics Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / MicroARNs / Neoplasias Pulmonares Límite: Humans Idioma: En Revista: Clin Epigenetics Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania