LncRNA RPPH1 promotes colorectal cancer metastasis by interacting with TUBB3 and by promoting exosomes-mediated macrophage M2 polarization.
Cell Death Dis
; 10(11): 829, 2019 11 04.
Article
en En
| MEDLINE
| ID: mdl-31685807
ABSTRACT
Metastasis is a well-known poor prognostic factor in cancer. However, the mechanisms how long non-coding RNAs (lncRNAs) regulate metastasis in colorectal cancer (CRC) remain largely unknown. Besides, tumor-associated macrophages (TAMs) play an important role in tumor progression, yet the contribution of lncRNA-mediated crosstalk between TAMs and CRC cells to tumor progression is not well understood. In this study, we report that lncRNA RPPH1 was significantly upregulated in CRC tissues, and the RPPH1 overexpression was associated with advanced TNM stages and poor prognosis. RPPH1 was found to promote CRC metastasis in vitro and in vivo. Mechanistically, RPPH1 induced epithelial-mesenchymal transition (EMT) of CRC cells via interacting with ß-III tubulin (TUBB3) to prevent its ubiquitination. Furthermore, CRC cell-derived exosomes transported RPPH1 into macrophages which mediate macrophage M2 polarization, thereby in turn promoting metastasis and proliferation of CRC cells. In addition, exosomal RPPH1 levels in blood plasma turned out to be higher in treatment-naive CRC patients but lower after tumor resection. Compared to CEA and CA199, exosomal RPPH1 in CRC plasma displayed a better diagnostic value (AUC = 0.86). Collectively, RPPH1 serves as a potential therapeutic and diagnostic target in CRC.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Tubulina (Proteína)
/
ARN Neoplásico
/
Neoplasias Colorrectales
/
Exosomas
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ARN Largo no Codificante
/
Macrófagos
/
Proteínas de Neoplasias
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Cell Death Dis
Año:
2019
Tipo del documento:
Article
País de afiliación:
China