RESUMO
NCAPG2 is a component of the condensin II complex and contributes to chromosome segregation via microtubule-kinetochore attachment during mitosis. It is well known that NCAPG2 plays a critical role in cell mitosis; however, the role of altered NCAPG2 expression and its transcriptional regulatory function in cancer development remains mostly unknown. Here, for the first time we reported that NCAPG2 was evidently increased in non-small cell lung cancer tissues compared to adjacent normal lung tissues. Clinicopathological data analysis showed that NCAPG2 overexpression was significantly correlated with lymph node metastasis and pathologic-Tumour Nodes Metastasen stages, and was an independent prognostic factor in lung adenocarcinoma patients. Moreover, siRNA-mediated knockdown of NCAPG2 could inhibit tumour cell growth of lung adenocarcinoma cells (A549 and H1299) in vitro and could significantly lead to cell cycle arrest in the G2 phase. Furthermore, we found that NCAPG2 silencing significantly decreased the expression levels of G2/M phase cell cycle-related protein expressions (Cyclin B1, Cdc2) and increased the expression levels of p27 and p21 through Western blot analysis. Taken together, we demonstrated that increased NCAPG2 expression could regulate cell proliferation and identified as a poor prognostic biomarker in lung adenocarcinoma.
Assuntos
Adenocarcinoma/genética , Adenocarcinoma/patologia , Proteínas Cromossômicas não Histona/genética , Fase G2 , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mitose , Adenocarcinoma de Pulmão , Idoso , Pontos de Checagem do Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Proteínas Cromossômicas não Histona/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Inativação Gênica , Humanos , Masculino , Análise Multivariada , Prognóstico , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , RNA Interferente Pequeno/metabolismo , Análise de Sobrevida , Regulação para Cima/genética , Quinase 1 Polo-LikeRESUMO
BACKGROUND: Protein regulator of cytokinesis-1 (PRC1) belongs to the microtubule-associated proteins (MAPs) family, and is involved in cytokinesis. Recent investigations suggest PRC1 involvement in human carcinogenesis, including breast carcinoma, hepatocellular carcinoma and etc. However, whether PRC1 contributes to lung adenocarcinoma tumorigenesis remains unknown. METHODS: Quantitative reverse-transcription polymerase chain reaction (qRT-PCR), Western blotting and Immunohistochemical staining (IHC) were used to evaluate and contrast the PRC1 expression profile in lung adenocarcinoma and adjacent normal lung tissues. We examined the clinical use of PRC1 in lung adenocarcinoma prognosis. Additionally, the tumorigenesis impact of PRC1 in lung adenocarcinoma cells was verified via in vitro and in vivo metastasis and tumorigenesis assays. Notably, Next Generation Sequencing (NGS) was performed to investigate the molecular mechanism underlying the oncogenic role of PRC1 in lung adenocarcinoma. RESULTS: PRC1 mRNA and protein expressions were upregulated in lung adenocarcinoma tissues compared to adjacent normal lung tissues. PRC1 protein overexpression correlated with lymph node metastasis and was an independent poor prognostic factor for lung adenocarcinoma patients. Our data implied that PRC1 depletion limited the proliferation and invasion of lung adenocarcinoma cells in vitro and lowered tumor development and lung metastasis in vivo. Remarkably, limiting PRC1 substantially prompted G2/M phase cell cycle arrest and apoptosis. Mechanistically, by conducting NGS on PRC1-depleted A549 cells and control cells, we discovered that PRC1 expression was significantly correlated with the Wnt signaling pathway. CONCLUSIONS: This investigation offers confirmation that PRC1 is a prognostic and promising therapeutic biomarker for people with lung adenocarcinoma and takes on a key part in the activation of the Wnt/ß-catenin pathway in lung adenocarcinoma development.
Assuntos
Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Via de Sinalização Wnt/fisiologia , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma de Pulmão , Idoso , Animais , Apoptose/genética , Linhagem Celular Tumoral , Feminino , Pontos de Checagem da Fase G2 do Ciclo Celular/genética , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Prognóstico , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina/genética , beta Catenina/metabolismoRESUMO
BACKGROUND: With the release of the National Lung Screening Trial results, the detection of peripheral pulmonary lesions (PPLs) is likely to increase. Computed tomography (CT)-guided percutaneous transthoracic needle biopsy (PTNB) and radial probe endobronchial ultrasound (r-EBUS)-guided transbronchial lung biopsy (TBLB) are recommended for tissue diagnosis of PPLs. METHODS: A systematic review of published literature evaluating the accuracy of r-EBUS-TBLB and CT-PTNB for the diagnosis of PPLs was performed to determine point sensitivity and specificity, and to construct a summary receiver-operating characteristic curve. RESULTS: This review included 31 publications dealing with EBUS-TBLB and 14 publications dealing with CT-PTNB for the diagnosis of PPLs. EBUS-TBLB had point sensitivity of 0.69 (95% CI: 0.67-0.71) for the diagnosis of peripheral lung cancer (PLC), which was lower than the sensitivity of CT-PTNB (0.94, 95% CI: 0.94-0.95). However, the complication rates observed with EBUS-TBLB were lower than those reported for CT-PTNB. CONCLUSIONS: This meta-analysis showed that EBUS-TBLB is a safe and relatively accurate tool in the investigation of PLC. Although the yield remains lower than that of CT-PTNB, the procedural risks are lower.