Candidate tumor suppressor ZNF154 suppresses invasion and metastasis in NPC by inhibiting the EMT via Wnt/β-catenin signalling

Hu, Ying; Qi, Min‐Fang; Xu, Qianlan; Kong, Xiangyun; Cai, Rui; Chen, Qiuqiu; Tang, Hua-Ying; Jiang, Wei

doi:10.18632/oncotarget.20479

Cited by 24 publications

(19 citation statements)

References 29 publications

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“…Based on the aforementioned findings, we hypothesized that LHX2 may promote the progression of NPC. Further research revealed that existing literature had reported that the Wnt/β-catenin signaling pathway was closely related to the progression of NPC [25–28]. Moreover, a few studies have documented that LHX2 mediates the Wnt/β-catenin signaling pathway in the development of disease [29, 30].…”

Section: Resultsmentioning

confidence: 99%

RETRACTED ARTICLE: MicroRNA-506 inhibits tumor growth and metastasis in nasopharyngeal carcinoma through the inactivation of the Wnt/β-catenin signaling pathway by down-regulating LHX2

Liang

Zheng

Wang

et al. 2019

J Exp Clin Cancer Res

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Background Epithelial-mesenchymal transition (EMT)-associated proteins play key roles in cancer progression and metastasis with the involvement of microRNAs (miRNAs). This study aims to assess the role of miR-506 working in tandem with LIM Homeobox 2 (LHX2) in EMT and metastasis through the Wnt/β-catenin signaling pathway in nasopharyngeal carcinoma (NPC). Methods Differentially expressed genes associated with NPC were screened using microarray analyses, from which LHX2 was identified. Next, the potential relationship between miR-506 and LHX2 was analyzed. In order to explore the effect of miR-506 or LHX2 on NPC cell proliferation, migration, invasion and apoptosis, serials of mimics, inhibitors or siRNA against LHX2 were transfected into NPC cells. Then, the expression patterns of LHX2, Wnt1, β-catenin, E-cadherin, Vimentin, TCF4 and Twist were determined to assess the influence of miR-506 or LHX2 on EMT as well as the relationship between the Wnt/β-catenin signaling pathway and TCF4. The tumorigenicity and lymph node metastasis (LNM) in xenograft tumors of nude mice were observed. Results The has-miR-506-3p was identified as the down-regulated gene in NPC based on the microarray data while LHX2 was negatively regulated by miR-506. Over-expression of miR-506 or silencing of LHK2 inhibited NPC cell proliferation, migration, invasion, tumorigenicity and LNM but promoted apoptosis indicated by decreased Wnt1, β-catenin, Vimentin, TCF4 and Twist expressions along with increased E-cadherin expressions. Conclusions miR-506 inhibits tumor growth and metastasis in NPC via inhibition of Wnt/β-catenin signaling by down-regulating LHX2, accompanied by decreased TCF4. Taken together, miR-506 targeted-inhibition LHX2 presents a promising therapeutic strategy for the treatment of NPC. Trial registration ChiCTR1800018889 . Registered 15 October 2018. Electronic supplementary material The online version of this article (10.1186/s13046-019-1023-4) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

RETRACTED ARTICLE: MicroRNA-506 inhibits tumor growth and metastasis in nasopharyngeal carcinoma through the inactivation of the Wnt/β-catenin signaling pathway by down-regulating LHX2

Liang

Zheng

Wang

et al. 2019

J Exp Clin Cancer Res

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“…When we analyzed the patient data for the clinical course, we found a significant association between ZNF154 promoter hypermethylation and better postoperative survival (Figure 3, Table 2 and Table 3). A recent study has shown that ZNF154 methylation was associated with better survival in nasopharyngeal carcinoma [13]. In contrast, a different research group reported poor outcomes in loss of function of ZNF154 in prostate cancer [14].…”

Section: Discussionmentioning

confidence: 99%

Silenced ZNF154 Is Associated with Longer Survival in Resectable Pancreatic Cancer

Wiesmueller

Köpke

Aust

et al. 2019

IJMS

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Pancreatic cancer has become the third leading cause of cancer-related death in the Western world despite advances in therapy of other cancerous lesions. Late diagnosis due to a lack of symptoms during early disease allows metastatic spread of the tumor. Most patients are considered incurable because of metastasized disease. On a cellular level, pancreatic cancer proves to be rather resistant to chemotherapy. Hence, early detection and new therapeutic targets might improve outcomes. The detection of DNA promoter hypermethylation has been described as a method to identify putative genes of interest in cancer entities. These genes might serve as either biomarkers or might lead to a better understanding of the molecular mechanisms involved. We checked tumor specimens from 80 patients who had undergone pancreatic resection for promoter hypermethylation of the zinc finger protein ZNF154. Then, we further characterized the effects of ZNF154 on cell viability and gene expression by in vitro experiments. We found a significant association between ZNF154 hypermethylation and better survival in patients with resectable pancreatic cancer. Moreover, we suspect that the cell growth suppressor SLFN5 might be linked to a silenced ZNF154 in pancreatic cancer.

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“…Notably, a couple of studies have focused on how biomarkers regulate EMT in NPC (14,15). In addition, the aberrant activation of the Wnt/β-catenin pathway is commonly reported to be involved in the EMT process of NPC (16).…”

Section: Introductionmentioning

confidence: 99%

Keratin 6A gene silencing suppresses cell invasion and metastasis of nasopharyngeal carcinoma via the β‑catenin cascade

Chen

Shan

2019

Mol Med Report

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Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer. This study aimed to study the mechanisms of ectopic keratin 6A (KRT6A) in NPC. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were performed to detect KRT6A levels in NPC cell lines (C666-1, 5-8F and SUNE-1) and a nasopharyngeal epithelial cell line (NP69, as a control). After SUNE-1 NPC cells had been silenced by KRT6A, cell viability, metastasis and invasion were determined using Cell Counting Kit-8, wound healing and Transwell assays, respectively. KRT6A levels, metastasis-associated factors and the Wnt/β-catenin pathway were measured using RT-qPCR and western blotting. It was demonstrated that KRT6A was upregulated in all detected NPC cells, among which KRT6A was the highest in SUNE-1 cells. In SUNE-1 cells, cell viability was inhibited at 24 and 48 h, and that cell metastasis and invasion were demonstrated to be suppressed by KRT6A silencing. Both the mRNA and protein levels of KRT6A, matrix metalloproteinase (MMP)-2, MMP-9, β-catenin, lymphoid enhancer binding factor 1 and T-cell specific factor 4 were reduced in the small interfering (si)KRT6A group. However, the results demonstrated that the levels of epithelial-cadherin and tissue inhibitor of metalloproteinase-2 (TIMP-2) were promoted in the siKRT6A group. The activation of the Wnt/β-catenin pathway by lithium chloride reversed the effect of si-KRT6A by modulating the expression of MMP-2/9 and TIMP2. It was observed that KRT6A silencing suppressed cell invasion and metastasis of NPC via the β-catenin cascade. Together these results provide important insights into a novel approach for the diagnosis and treatment of NPC.

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Candidate tumor suppressor ZNF154 suppresses invasion and metastasis in NPC by inhibiting the EMT via Wnt/β-catenin signalling

Cited by 24 publications

References 29 publications

RETRACTED ARTICLE: MicroRNA-506 inhibits tumor growth and metastasis in nasopharyngeal carcinoma through the inactivation of the Wnt/β-catenin signaling pathway by down-regulating LHX2

RETRACTED ARTICLE: MicroRNA-506 inhibits tumor growth and metastasis in nasopharyngeal carcinoma through the inactivation of the Wnt/β-catenin signaling pathway by down-regulating LHX2

Silenced ZNF154 Is Associated with Longer Survival in Resectable Pancreatic Cancer

Keratin 6A gene silencing suppresses cell invasion and metastasis of nasopharyngeal carcinoma via the β‑catenin cascade

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