Circulating Methylated XAF1 DNA Indicates Poor Prognosis for Gastric Cancer

Ling, Zhi‐Qiang; Lv, Ping; Lu, Xiaoxiao; Yu, Jinming; Han, Jing; Liu, Ying; Zhu, Xin; Zhu, Wenxiu; Fang, Xian-Hua; Wang, Shi; Wu, Yichen

doi:10.1371/journal.pone.0067195

Cited by 55 publications

(43 citation statements)

References 31 publications

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“…The present study demonstrated an association between incidence of VM and reduced expression of XAF1; the incidence of VM was significantly increased in XAF1-underexpressing samples. This provides a novel fundamental mechanism for an effect reported previously that decreased XAF1 expression is associated with poor prognosis in numerous types of cancers (30,31).…”

Section: Discussionmentioning

confidence: 74%

Role of X-linked inhibitor of apoptosis-associated factor-1 in vasculogenic mimicry in ovarian cancer

Liu

Wang

Mao

2017

Molecular Medicine Reports

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X-linked inhibitor of apoptosis‑associated factor 1 (XAF1) was identified as a novel X-linked inhibitor of apoptosis (XIAP) binding partner that may reverse the anti‑apoptotic effect of XIAP. Previous studies have revealed that XAF1 serves an important role in cancer angiogenesis. Vasculogenic mimicry (VM) describes the formation of fluid‑conducting channels by highly invasive and genetically dysregulated tumor cells. VM is critical for tumor blood supply and is associated with aggressive actions and metastasis. The aim of present study was to investigate the potential association between XAF1 expression with VM of ovarian cancer, and evaluate the role of XAF1 in tumor cell migration and invasion of SKOV3 cells. VM structure and XAF1 expression were detected in 94 tissue samples of advanced epithelial ovarian cancer (EOC). Invasion and migration of the SKOV3 human ovarian carcinoma cell line were identified by Transwell assay. It was revealed that the presence of VM was associated with high grade advanced ovarian cancer. Reduced XAF1 expression was significantly associated with presence of VM. Overexpression of XAF1 significantly reduced invasion and migration of SKOV3 cells, and inhibited vascular endothelial growth factor protein expression. Furthermore, vasculature was suppressed by overexpression of XAF1 in vivo in xenograft models. In conclusion, XAF1 expression was associated with VM in ovarian cancer, suggesting a potential role of XAF1 in the formation of VM in EOC. These ﬁndings may facilitate the development of novel therapeutic agents for the treatment of ovarian cancer.

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Section: Discussionmentioning

confidence: 74%

Role of X-linked inhibitor of apoptosis-associated factor-1 in vasculogenic mimicry in ovarian cancer

Liu

Wang

Mao

2017

Molecular Medicine Reports

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“…For example, epigenetic patterns altered within the promoter region of XAF1 genes have been identified in tumors. Hypermethylation of CpGs sites located in the 5' proximal region was found to be associated with transcriptional silencing of XAF1 in gastric cancer (14,23), urogenital (24) and colon (25) cancer cell lines. However, epigenetic modifications are extremely complex and other XAF1 associations have been observed.…”

Section: Xaf1 Expression Levels In a Non-small Cell Lung Cancer Cohormentioning

confidence: 97%

XAF1 expression levels in a non-small cell lung cancer cohort and its potential association with carcinogenesis

et al. 2017

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The process of lung carcinogenesis is still not well understood and involves different levels of regulation of several genes. The search for molecular biomarkers, which can be applicable to clinical practice, has been the focus of various studies. XIAP-associated factor 1 (XAF1) was previously shown to be downregulated in many types of tumors, including squamous cell lung cancer. XAF1 is a pro-apoptotic protein and its restoration was found to sensitize cancer cells to apoptotic stimuli; however, the precise mechanism involved in the downregulation of XAF1 in tumors is unknown and promoter hypermethylation or heat-shock transcription factor 1 (HSF1) may be involved. Therefore, the aim of the present study was to evaluate the expression of XAF1 in tumors and adjacent non-tumor specimens from non-small cell lung cancer (NSCLC) patients, and its potential association with various factors including clinicopathological characteristics and other genes involved in NSCLC. Our results indicated that XAF1 expression was markedly altered in NSCLC tumor samples when compared to that found in normal lung tissues. Predominantly, XAF1 was downregulated in the tumors, except in never-smoker patients. In addition, XAF1 may also be important in the whole cell stress mechanism where the p53 status is crucial.

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“…The peroxidase activity was developed by incubating with 0.1% 3,3-diaminobenzidine (Sigma) in PBS with 0.05% H2O2 for 5 min at room temperature. As described methods in our previous studies [42,43], based on the frequency and intensity of staining, the scores of histochemical staining were determined by three independent clinical pathologists, and the inconsistent results were finally determined after discussion.…”

Section: Immunohistochemical Analysismentioning

confidence: 99%

“…The western blotting analysis was carried out using Immobilon-P polyvinylidene difluoride membranes (Millipore, 28820 Single Oak Drive, Temecula, California 92590, USA) as described in previous studies [42,43]. The cell lysates were separated on sodium dodecyl sulfate-polyacrylamide gels and the western blotting analysis was carried out with following antibodies against CSMD1, Cyclin D1 (Santa Cruz Biotechnology), Snail (Abgent Inc, CA, USA), E-cadherin, Vimentin, Twist, Zeb1 (Cell Signaling Technology, MA, USA), iNOS, NFκB-p65, NFκB-p50 (Abcam, Cambridge, CB4 0FL, UK), and c-MYC (Sigma Chemical Co., MO, USA), respectively.…”

Section: Western Blotting Analysismentioning

confidence: 99%

Deregulation of CSMD1 targeted by microRNA-10b drives gastric cancer progression through the NF-κB pathway

et al. 2019

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Aim:This study aimed to investigate the oncogenic activity of microRNA-10b by targeting CUB and sushi multiple domains protein 1 (CSMD1) in human gastric cancer (GC) and the underlying mechanisms. Methods: The expression of CSMD1 in human GC tissues was evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR), immunoblotting, and immunohistochemical analysis. The expressive abundance of microRNA-10b was detected by stem-loop RT-PCR. Molecular and cellular techniques, including lentiviral vector-mediated knockdown or overexpression, were used to elucidate the effect of microRNA-10b on the expression of CSMD1. Results: CSMD1 was targeted and downregulated by microRNA-10b in human GC tissues and cells, and the down-regulated expression of CSMD1 contributed to poor survival. The knockdown of microRNA-10b expression inhibited cell proliferation in GC cells in vitro and tumor growth in vivo. The inhibition of microRNA-10b expression repressed invasion and migration of HGC27 cells and retarded GC cells metastasis to the liver in Balb/c nude mice. The up-regulated expression of microRNA-10b promoted the proliferation and metastasis of MKN74 cell in vitro. Intratumoral injection of microRNA-10b mimic also promoted the growth and metastasis of tumor xenografts in Balb/c nude mice. Mechanistically, microRNA-10b promoted the invasion and metastasis of human GC cells through inhibiting the expression of CSMD1, leading to the activation of the nuclear factor-κB (NF-κB) pathway that links inflammation to carcinogenesis, subsequently resulting in the upregulation of c-Myc, cyclin D1 (CCND1), and epithelial-mesenchymal transition (EMT) markers. Conclusions: The findings established that microRNA-10b is an oncomiR that drives metastasis. Moreover, a set of critical tumor suppressor mechanisms was defined that microRNA-10b overcame to drive human GC progression.

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Circulating Methylated XAF1 DNA Indicates Poor Prognosis for Gastric Cancer

Cited by 55 publications

References 31 publications

Role of X-linked inhibitor of apoptosis-associated factor-1 in vasculogenic mimicry in ovarian cancer

Role of X-linked inhibitor of apoptosis-associated factor-1 in vasculogenic mimicry in ovarian cancer

XAF1 expression levels in a non-small cell lung cancer cohort and its potential association with carcinogenesis

Deregulation of CSMD1 targeted by microRNA-10b drives gastric cancer progression through the NF-κB pathway

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