scholarly journals miR-875-5p exerts tumor-promoting function via down-regulation of CAPZA1 in esophageal squamous cell carcinoma

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10020
Author(s):  
Nan Kang ◽  
Yunwei Ou ◽  
Guangchao Wang ◽  
Jie Chen ◽  
Dan Li ◽  
...  

Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer deaths worldwide. Currently, efficient genetic markers for diagnosis and treatment of ESCC are lacking. MicroRNAs (miRNAs) are global genetic regulators that control cancer gene expression by binding to the 3′untranslated regions (3′UTRs) of targeting mRNAs. In addition, miRNAs function as oncogenes or tumor suppressors in the progression of tumors. In the current study, we found that hsa-miR-875-5p (miR-875-5p) exhibited amplification in ESCC according to the TCGA database. Then, xCELLigence Real-Time Cell Analyzer (RTCA)-MP system and colony formation assays were employed to detect cell proliferationand colony formationability. The results showed that miR-875-5p promoted the proliferation ESCC cells. Subsequently, transwell results indicated that miR-875-5p promoted the invasion and migration of ESCC cells. Furthermore, we showed that miR-875-5p was able to bind to CAPZA13’UTR, which contains the single nucleotide polymorphism (SNP), rs373245753, as reported in our previous study involving WGS and WES on ESCC. Subsequently, mRNA affinity pull-down assays verifiedthat the SNP disrupts miR-875-5p binding to CAPZA1. The current study is the first demonstration that miR-875-5p may function as an oncogene via down-regulation of CAPZA1 expression in ESCC.


2020 ◽  
Vol 20 ◽  
Author(s):  
Wenbin Wu ◽  
Yangmei Zhang ◽  
Xiaowu Li ◽  
Xiang Wang ◽  
Yuan Yuan

Objective: The purpose of this study was to explore the mechanism of the miR-375/XPR1 axis in esophageal squamous cell carcinoma (ESCC) and provide a new idea for targeted therapy of ESCC. Methods: Differentially expressed genes in GEO and TCGA databases were analyzed by bioinformatics. The expression levels of miR-375 and XPR1 mRNA were detected by qRT-PCR. Protein expression of XPR1 was detected by western blot. Bioinformatics analysis and dual luciferase assay were conducted to confirm the targeting relationship between miR-375 and XPR1. The viability, proliferation, migration and invasion of cells in each treatment group were detected by CCK-8, colony formation, wound healing and Transwell assays. Results: Significantly down-regulated miR-375 and remarkably up-regulated XPR1 were observed in ESCC tissue and cells. Overexpression of miR-375 inhibited proliferation, invasion and migration of ESCC cells, and greatly reduced the promoting effect of XPR1 overexpression on cell proliferation, migration and invasion. Dual luciferase assay confirmed that miR-375 targeted and inhibited XPR1 expression in ESCC. Conclusion: These results demonstrate the regulatory role of the miR-375/XPR1 axis in ESCC cells and provide a new potential target for the precise treatment of patients with ESCC.





2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Jindong Li ◽  
Chengyan Jin ◽  
Lihua Sun ◽  
Bin Wang ◽  
Peiyan Hua ◽  
...  

Abstract Objective Although esophageal squamous cell carcinoma (ESCC)-oriented mechanism has been widely explored, the integrated action of histone deacetylase 2 (HDAC2), microRNA (miR)-503-5p and C-X-C motif chemokine 10 (CXCL10) in ESCC has not been thoroughly explored. Thus, we performed the research to study the role of HDAC2/miR-503-5p/CXCL10 axis in ESCC. Methods ESCC tissues and mucosal tissues (5 cm from cancer tissues) were collected, in which HDAC2, miR-503-5p and CXCL10 expression levels were tested. The mechanism of HDAC2, miR-503-5p and CXCL10 was interpreted. The viability, colony formation ability, apoptosis, invasion and migration abilities of ESCC cells were tested after HDAC2, miR-503-5p or CXCL10 expression was altered. Tumorigenesis in mice was observed to further verify the in vitro effects of HDAC2 and miR-503-5p. Results HDAC2 and CXCL10 were up-regulated while miR-503-5p was down-regulated in ESCC. HDAC2 bound to miR-503-5p and miR-503-5p targeted CXCL10. Silencing HDAC2 or restoring miR-503-5p depressed viability, colony-forming, invasion and migration abilities and enhanced apoptosis of ESCC cells in vitro, as well as suppressed ESCC tumorigenesis in vivo. Inhibition of miR-503-5p or elevation of CXCL10 negated HDAC2 knockout-induced effects on ESCC cells. Conclusion This work elucidates that HDAC2 knockdown retards the process of ESCC by elevating miR-503-5p and inhibiting CXCL10 expression, which may provide a guidance for ESCC management.



2019 ◽  
Vol Volume 12 ◽  
pp. 9319-9327 ◽  
Author(s):  
Quan Chen ◽  
Yiming Zheng ◽  
Bingbing Wu ◽  
Xia Chen ◽  
Fei Sun ◽  
...  


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hanjing Gao ◽  
Zheng Yan ◽  
Haiyan Sun ◽  
Yanfang Chen

Abstract Background It has been reported that Forkhead transcription family member (FOXA2) regulates esophageal squamous cell carcinoma (ESCC) progression. However, the specific mechanism, by which FOXA2 promotes ESCC malignant progression, remains unclear. Materials and methods QRT-PCR and western blotting were applied to measure FOXA2 expression in ESCC tissues, while CCK-8 assay and Transwell assays were used to investigate the effect of FOXA2 on ESCC. Luciferase reporter assay, followed by fast chromatin immunoprecipitation (ChIP) assay, was used to study the relationship between FOXA2 and ZEB2. Results FOXA2 was significantly increased in ESCC tissues, when compared to normal tissues. Moreover, high expression of FOXA2 was also found in ESCC cells. Knockdown of FOXA2 inhibited ESCC cell proliferation, invasion, and migration. Mechanically, FOXA2 was verified to regulate ZEB2 expression at transcription level. Moreover, ZEB2 reversed the inhibitory effect of FOXA2 on ESCC proliferation, invasion, and migration. The relationship between ZEB2 and FOXA2 in ESCC tissues was negative. Conclusions These results indicate that FOXA2 plays a critical role in ESCC progression and may become a potential candidate target for ESCC treatment.



2014 ◽  
Vol 59 (19) ◽  
pp. 2232-2239 ◽  
Author(s):  
Baoyu Liang ◽  
Yan Wu ◽  
Xu Han ◽  
Xiaofei Zheng ◽  
Qimin Zhan ◽  
...  


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