Beclin 1 promotes apoptosis and decreases invasion by upregulating the expression of ECRG4 in A549 human lung adenocarcinoma cells

Wang, Wenyu; Fan, Haoyi; Li, Xiaoyan; Wu, Gang; Wenju, Zhao; Zhang, Guihong; Li, Linwei

doi:10.3892/mmr.2016.5219

Cited by 15 publications

(13 citation statements)

References 15 publications

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“…This conclusion was consistent with previous researches in vitro, which showed that overexpression of Beclin-1 inhibited the proliferation and invasion of A549 human lung adenocarcinoma cells, while knockdown of Beclin-1 promoted the proliferation of A549 cells. 43 , 44 Another meta-analysis investigated the clinicopathological significance of Beclin-1 in gastric cancer, and reached similar conclusions. In that meta-analysis, high level of Beclin-1 was associated with better differentiation and earlier TNM stage, but the level of Beclin-1 was not associated with lymph nodal involvement.…”

Section: Discussionmentioning

confidence: 65%

Prognostic and clinicopathological significance of Beclin-1 in non-small-cell lung cancer: a meta-analysis

Zheng¹,

Li²,

et al. 2018

OTT

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BackgroundAutophagy plays a key role in the development of non-small-cell lung cancer (NSCLC). Beclin-1 is essential for the initiation and regulation of autophagy. Accumulated studies have investigated the prognostic role of Beclin-1 in NSCLC, but conclusions remain controversial. Therefore, we conducted this meta-analysis to assess the potential significance of Beclin-1 in NSCLC.Materials and methodsPubMed and Embase databases were searched for eligible studies published before December 31, 2017. Odds ratio (OR) was pooled to evaluate the clinicopathological significance of Beclin-1 in NSCLC. Hazard ratio (HR) was adopted to assess the association of Beclin-1 with overall survival (OS).ResultsEight studies involving 1,159 patients were included in this meta-analysis. The pooled results showed that high Beclin-1 expression was significantly correlated with earlier tumor grade (OR=0.54, 95% CI: 0.36–0.81, P=0.003), less nodal involvement (OR=0.56, 95% CI: 0.37–0.86, P=0.007), earlier TNM stage (OR=0.62, 95% CI: 0.43–0.89, P=0.010), smaller tumor size (OR=0.54, 95% CI: 0.36–0.81, P=0.003), better differentiation (OR=0.48, 95% CI: 0.36–0.64, P<0.001), and less recurrence (OR=0.24, 95% CI: 0.14–0.41, P<0.001). Moreover, high level of Beclin-1 was significantly associated with better OS in NSCLC (HR=0.41, 95% CI: 0.26–0.64, P<0.001).ConclusionOur meta-analysis suggests that high Beclin-1 expression predicts a better clinicopathological status and a better prognosis in NSCLC. Beclin-1 might act as a promising prognostic biomarker for NSCLC.

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Section: Discussionmentioning

confidence: 65%

Prognostic and clinicopathological significance of Beclin-1 in non-small-cell lung cancer: a meta-analysis

Zheng¹,

Li²,

et al. 2018

OTT

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“…In contrast, autophagic induction leads to decreased migration and invasion in glioblastoma cells, whereas autophagy deficiency increased cell motility and invasiveness [ 45 ]. In A549 human lung adenocarcinoma cells, Beclin1 promotes apoptosis and reduces invasion [ 49 ], whereas knockdown of Beclin1 decreased invasion and metastasis in osteosarcoma cells [ 50 ]. Our data clearly show that Beclin1 silencing led to reduced migration of osteosarcoma cells, and thus, it is likely that the effect of Beclin1 on cancer cell metastasis is cell type dependent.…”

Section: Discussionmentioning

confidence: 99%

Novel oncogene COPS3 interacts with Beclin1 and Raf-1 to regulate metastasis of osteosarcoma through autophagy

Zhang

Yan

Guo

et al. 2018

J Exp Clin Cancer Res

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BackgroundExpression of COP9 signalosome subunit 3 (COPS3), an oncogene overexpressed in osteosarcoma, has been demonstrated to be significantly correlated with tumor metastasis. However, the underlying mechanism by which COPS3 promotes metastasis of osteosarcoma and its role in autophagy remain unknown.MethodsThe expression of COPS3 was detected in primary osteosarcoma tissues and matching lung metastasis tissues by immunohistochemistry (IHC). The effect of COPS3 on the metastasis of osteosarcoma cells was investigated by transwell, wound healing assays and animal studies. Indicated proteins was analyzed by western blotting when COPS3 was knockdown or overexpressed. The COPS3 Interacting protein was determined by immunoprecipitation assay. The relationship between COPS3 and autophagy was detected by western blotting and immunofluorescence.ResultsWe found that knockdown of COPS3 significantly reduced the lung metastasis of osteosarcoma cells in a mouse model, coinciding with downregulation of mitogen-activated protein kinase (MEK) and extracellular signal-regulated kinase (ERK) signaling. The silencing of COPS3 also inhibited the epithelial–mesenchymal transition (EMT) through the 90 kDa ribosomal S6 kinases (RSK), a family of signal transduction proteins downstream of MEK/ERK. Reciprocal immunoprecipitation assays revealed that COPS3 directly interacts with Raf-1, an upstream regulator of MEK/ERK. Surprisingly, Beclin1, an important autophagic protein, appeared in the COPS3-immunoprecipitates, along with the autophagic markers LC3-I and LC3-II. Loss of COPS3 completely inhibited H2O2-induced autophagic flux and reduced Beclin1 expression. Additionally, autophagy inhibitor or silencing of Beclin1 both decreased cell metastasis.ConclusionsTaken together, these data reveal a novel function of COPS3 in the regulation of autophagy and highlight the relationship between autophagy and metastasis in osteosarcoma cells.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0791-6) contains supplementary material, which is available to authorized users.

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“…Moreover, the function of Beclin1 in apoptosis has been investigated in many studies. A recent research showed that Beclin1 regulated apoptosis by binding to the anti-apoptotic members of the Bcl family such as Bcl-2, Bcl-xl and Bcl-w through the BH3 domain ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

Beclin1 overexpression suppresses tumor cell proliferation and survival via an autophagy‑dependent pathway in human synovial sarcoma cells

Zhu

Cai

et al. 2018

Oncol Rep

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Beclin1 is an important autophagy-related protein, which is involved in both autophagy and apoptosis. In recent years, the antitumor effect of Beclin1 has received increased attention. In the present study, we established a stable Beclin1-overexpressing cell line with SW982 human synovial sarcoma cells. We found that Beclin1 overexpression decreased the cell viability, inhibited proliferation and induced apoptosis in SW982 cells. The expression levels of Bcl-2 and PCNA were decreased, while the levels of cleaved-caspase-3 and cleaved-PARP were increased. Beclin1 is closely related with autophagy, thus the autophagy-related markers LC3 and p62 were detected by western blot analysis, and transmission electron microscopy was used to observe autophagosomes. The results showed that the expression level of LC3II was increased and that of p62 was decreased. Moreover, many double membrane-enclosed autophagosomes were found in cells with Beclin1 overexpression, which indicated that the autophagic activity was enhanced. To explore the effect of autophagy on the viability of SW982 cells, Atg5 was knocked down using siRNA to inhibit the autophagic activity. We found that autophagy contributed to the decrease in cell viability. Knockdown of Atg5 increased the viability and decreased the apoptotic rate of SW982 cells with Beclin1 overexpression. The expression level of Bcl-2 was increased, while the expression levels of cleaved-caspase-3 and cleaved-PARP were decreased. We also found that the Akt/Bcl-2/caspase-9 pathway was involved. The phosphorylation of AKT was positively correlated with cell viability. The cleavage of caspase-9 was increased by Beclin1 overexpression and decreased by inhibition of autophagy. Altogether, our results suggested that both autophagy and apoptosis contributed to the antitumor effect of Beclin1 in SW982 cells.

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Beclin 1 promotes apoptosis and decreases invasion by upregulating the expression of ECRG4 in A549 human lung adenocarcinoma cells

Cited by 15 publications

References 15 publications

Prognostic and clinicopathological significance of Beclin-1 in non-small-cell lung cancer: a meta-analysis

Prognostic and clinicopathological significance of Beclin-1 in non-small-cell lung cancer: a meta-analysis

Novel oncogene COPS3 interacts with Beclin1 and Raf-1 to regulate metastasis of osteosarcoma through autophagy

Beclin1 overexpression suppresses tumor cell proliferation and survival via an autophagy‑dependent pathway in human synovial sarcoma cells

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