SLFN5 suppresses cancer cell migration and invasion by inhibiting MT1-MMP expression via AKT/GSK-3β/β-catenin pathway

Wan, Guoqing; Liu, Yihao; Zhu, Jiang; Guo, Lijuan; Li, Chenhong; Yang, Yanwen; Gu, Xuefeng; Deng, Lili; Lu, Changlian

doi:10.1016/j.cellsig.2019.03.004

Cited by 55 publications

(56 citation statements)

References 46 publications

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“…The biological role of MMP14 was also determined using siRNA to silence its expression. Consistent with a previous study 32 , MMP14 silencing suppressed migration and invasion of RCC cells and alleviated the pro-migration and -invasion effect of circPTCH1 on RCC cells ( Figure S5 ). In addition, knockdown of circPTCH1 decreased the protein level of MMP14, while co-transfection with the miR-485-5p inhibitor partially restored its expression (Figure 5 G).…”

Section: Resultssupporting

confidence: 92%

circPTCH1 promotes invasion and metastasis in renal cell carcinoma via regulating miR-485-5p/MMP14 axis

Liu¹,

Hu²,

Wang³

et al. 2020

Theranostics

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Background: Circular RNAs (circRNAs) are a new class of non-coding RNAs (ncRNAs) that are derived from exons or introns by special selective shearing. circRNAs have been shown to play critical roles in various human cancers. However, their roles in renal cell carcinoma (RCC) and the underlying mechanisms remain largely unknown. Methods: A novel circRNA-circPTCH1, was identified from a microarray analysis of five paired RCC tissues. Then, we validated its expression and characterization through qRT-PCR, gel electrophoresis, RNase R digestion assays and Sanger sequencing. Functional experiments were performed to determine the effect of circPTCH1 on RCC progression both in vitro and in vivo . The interactions between circPTCH1 and miR-485-5p were clarified by RNA pull-down, luciferase reporter and RNA immunoprecipitation (RIP) assays. Results: We observed that circPTCH1 was up-regulated in RCC cell lines and tumor samples, and higher levels of circPTCH1 were significantly correlated with worse patient survival, advanced Fuhrman grade and greater risk of metastases. Elevated circPTCH1 expression led to increased migration and invasion of RCC cells both in vitro and in vivo whereas silencing circPTCH1 decreased migration and invasion and impeded the epithelial-mesenchymal transition (EMT) of RCC cells. Mechanistically, we elucidated that circPTCH1 could directly bind miR-485-5p and subsequently suppress expression of the target gene MMP14. Conclusion: circPTCH1 promotes RCC metastasis via the miR-485-5p/MMP14 axis and activation of the EMT process. Targeting circPTCH1 may represent a promising therapeutic strategy for metastatic RCC.

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Section: Resultssupporting

confidence: 92%

circPTCH1 promotes invasion and metastasis in renal cell carcinoma via regulating miR-485-5p/MMP14 axis

Liu¹,

Hu²,

Wang³

et al. 2020

Theranostics

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“…Few studies observed a positive correlation between SLFN5 and shorter overall survival [22,23]. Yet, most authors report a connection between SLFN5 and longer survival or less invasive growth, underlining that SLFN5 is a tumor suppressor [24,25,26,27]. These findings concur with our observation that increased survival in pancreatic cancer patients is linked to silenced ZNF154 , which, in turn, might translate into lower levels of SLFN5 .…”

Section: Discussionsupporting

confidence: 90%

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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“…In this study, we found that RUNX1 promotes β-catenin expression and activates Wnt signalling, and some transcription factors, such as LEF1, which can repress E-cadherin, are also activated. Previous studies have shown that MMPs are associated with the occurrence of EMT [38], while MMPs are regulated by Wnt/β-catenin signalling pathways [39–42].…”

Section: Discussionmentioning

confidence: 99%

RUNX1 promotes tumour metastasis by activating the Wnt/β-catenin signalling pathway and EMT in colorectal cancer

Lai

et al. 2019

J Exp Clin Cancer Res

143

115

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Background Runt-related transcription factor 1 (RUNX1) plays the roles of an oncogene and an anti-oncogene in epithelial tumours, and abnormally elevated RUNX1 has been suggested to contribute to the carcinogenesis of colorectal cancer (CRC). However, the mechanism remains unclear. Methods The expression of RUNX1 in CRC and normal tissues was detected by real-time quantitative PCR and Western blotting. The effect of RUNX1 on CRC migration and invasion was conducted by functional experiments in vitro and in vivo. Chromatin Immunoprecipitation assay verified the direct regulation of RUNX1 on the promoter of the KIT, which leads to the activation of Wnt/β-catenin signaling. Results RUNX1 expression is upregulated in CRC tissues. Upregulated RUNX1 promotes cell metastasis and epithelial to mesenchymal transition (EMT) of CRC both in vitro and in vivo. Furthermore, RUNX1 can activate Wnt/β-catenin signalling in CRC cells by directly interacting with β-catenin and targeting the promoter and enhancer regions of KIT to promote KIT transcription. These observations demonstrate that RUNX1 upregulation is a common event in CRC specimens and is closely correlated with cancer metastasis and that RUNX1 promotes EMT of CRC cells by activating Wnt/β-catenin signalling. Moreover, RUNX1 is regulated by Wnt/β-catenin. Conclusion Our findings first demonstrate that RUNX1 promotes CRC metastasis by activating the Wnt/β-catenin signalling pathway and EMT. Electronic supplementary material The online version of this article (10.1186/s13046-019-1330-9) contains supplementary material, which is available to authorized users.

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SLFN5 suppresses cancer cell migration and invasion by inhibiting MT1-MMP expression via AKT/GSK-3β/β-catenin pathway

Cited by 55 publications

References 46 publications

circPTCH1 promotes invasion and metastasis in renal cell carcinoma via regulating miR-485-5p/MMP14 axis

circPTCH1 promotes invasion and metastasis in renal cell carcinoma via regulating miR-485-5p/MMP14 axis

Silenced ZNF154 Is Associated with Longer Survival in Resectable Pancreatic Cancer

RUNX1 promotes tumour metastasis by activating the Wnt/β-catenin signalling pathway and EMT in colorectal cancer

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