Sirtuin 7 promotes nonsmall cell lung cancer progression by facilitating G1/S phase and epithelialmesenchymal transition and activating AKT and ERK1/2 signaling.
Oncol Rep
; 44(3): 959-972, 2020 09.
Article
em En
| MEDLINE
| ID: mdl-32705247
ABSTRACT
Increasing evidence has indicated the roles of sirtuin 7 (SIRT7) in numerous human cancers. However, the effects and the clinical significance of SIRT7 in human lung cancer is largely unknown. The present research demonstrated that SIRT7 was increased in human lung cancer tumor tissues. SIRT7 upregulation was associated with clinicopathological characteristics of lung cancer malignancy including positive lymph node metastasis, high pathologic stage and large tumor size. SIRT7 was also upregulated in human nonsmall cell lung cancer (NSCLC) cell lines. Furthermore SIRT7overexpressed A549 (A549SIRT7) and SIRT7knocked down H292 (H292shSIRT7) human NSCLC cell lines were established. Using these NSCLC cells and xenograft mouse models, it was revealed that SIRT7 overexpression markedly promoted growth and G1 to S cell cycle phase transition as well as migration, invasion and distant lung metastasis in A549 NSCLC cells, whereas SIRT7 knockdown suppressed these processes in H292 NSCLC cells. Mechanistically, in A549 NSCLC cells, SIRT7 overexpression significantly activated not only protein kinase B (AKT) signaling but also extracellular signalregulated kinase 1/2 (ERK1/2) signaling. SIRT7 overexpression also significantly downregulated cyclindependent kinase (CDK) inhibitors including p21 and p27 as well as upregulated cyclins including cyclin D1 and cyclin E1, and CDKs including CDK2 and CDK4. Notably, the epithelialmesenchymal transition (EMT) process of A549 NSCLC cells was facilitated by SIRT7 overexpression, as evidenced by Ecadherin epithelial marker downregulation and mesenchymal markers (Ncadherin, vimentin, Snail and Slug) upregulation. In addition, SIRT7 knockdown in H292 NSCLC cells exhibited the opposite regulatory effects. Moreover, inhibition of AKT signaling abated the promoting effects of SIRT7 in NSCLC cell proliferation and EMT progression. The present data indicated that SIRT7 accelerated human NSCLC cell growth and metastasis possibly by promotion of G1 to Sphase transition and EMT through modulation of the expression of G1phase checkpoint molecules and EMT markers as well as activation of AKT and ERK1/2 signaling. SIRT7 could be an innovative potential target for human NSCLC therapy.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação Neoplásica da Expressão Gênica
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Carcinoma Pulmonar de Células não Pequenas
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Sirtuínas
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Neoplasias Pulmonares
Tipo de estudo:
Observational_studies
/
Prognostic_studies
Limite:
Aged80
Idioma:
En
Revista:
Oncol Rep
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2020
Tipo de documento:
Article