scholarly journals Protein deubiquitylase USP3 stabilizes Aurora A to promote proliferation and metastasis of esophageal squamous cell carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ke Shi ◽  
Jin Zhong Zhang ◽  
Liang Yang ◽  
Ning-Ning Li ◽  
Ying Yue ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Malignant Cell ◽  
Clinical Samples ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Proliferation And Metastasis ◽  
Proliferation And Invasion

AbstractAurora A kinase is a cell cycle regulator that is dysregulated in several different malignancies. Nevertheless, its regulatory mechanisms are still not fully understood. Here, we report that ubiquitin specific peptidase 3 (USP3) promotes proliferation and metastasis of esophageal squamous cell carcinoma (ESCC) cells by mediating deubiquitination of Aurora A. Analysis of human clinical samples indicated that USP3 and Aurora A are highly expressed in ESCC. Cellular experiments confirmed that high expression of USP3 and Aurora A in ESCC cells promoted malignant cell proliferation and invasion. In this mechanism, USP3 leads to suppression of Aurora A ubiquitination, resulting less proteasome degradation. We constructed the deubiquitinated mimetic K143R of Aurora A and found that K143R significantly promoted the proliferation and invasion of ESCC cells and was not regulated by the deubiquitination of USP3. Moreover, Aurora A K143R potentiated the kinase activity of Aurora A in ESCC cells. Thus, our findings demonstrate that the tumorigenic feature of ESCC is in part mediated by USP3-facilitated deubiquitination of Aurora A.

scholarly journals Original Research: miR-194 inhibits proliferation and invasion and promotes apoptosis by targeting KDM5B in esophageal squamous cell carcinoma cells

2016 ◽  
Vol 242 (1) ◽  
pp. 45-52 ◽  
Author(s):  
Guanghui Cui ◽  
Donglei Liu ◽  
Weihao Li ◽  
Yuhang Li ◽  
Youguang Liang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Target Prediction ◽  
Underlying Mechanism ◽  
Carcinoma Cells ◽  
Original Research ◽  
Proliferation And Invasion

Increasing evidence suggests that miR-194 is down-regulated in esophageal squamous cell carcinoma tumor tissue. However, the role and underlying mechanism of miR-194 in esophageal squamous cell carcinoma have not been well defined. We used DIANA, TargetScan and miRanda to perform target prediction analysis and found KDM5B is a potential target of miR-194. Based on these findings, we speculated that miR-194 might play a role in esophageal squamous cell carcinoma development and progression by regulation the expression of KDM5B. We detected the expression of miR-194 and KDM5B by quantitative real-time reverse transcription PCR (qRT-PCR) and Western blot assays, respectively, and found down-regulation of miR-194 and up-regulation of KDM5B existed in esophageal squamous cell carcinoma cell lines. By detecting proliferation, invasion and apoptosis of TE6 and TE14 cells transfected with miR-194 mimics or mimic control, miR-194 was found to inhibit proliferation and invasion and promote apoptosis of esophageal squamous cell carcinoma cells. miR-194 was further verified to regulate proliferation, apoptosis and invasion of esophageal squamous cell carcinoma cells by directly targeting KDM5B. Furthermore, animal studies were performed and showed that overexpression of miR-194 inhibited the growth of esophageal squamous cell carcinoma tumors in vivo. These results confirmed our speculation that miR-194 targets KDM5B to inhibit esophageal squamous cell carcinoma development and progression. These findings offer new clues for esophageal squamous cell carcinoma development and progression and novel potential therapeutic targets for esophageal squamous cell carcinoma.

scholarly journals Long Non-Coding RNA CCAT2 Promotes the Development of Esophageal Squamous Cell Carcinoma by Inhibiting miR-200b to Upregulate the IGF2BP2/TK1 Axis

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaodan Wu ◽  
Yihui Fan ◽  
Yupeng Liu ◽  
Biao Shen ◽  
Haimin Lu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Clinical Samples ◽  
Non Coding Rna

Long non-coding RNAs (lncRNAs) have been shown to play important roles in human cancers, including esophageal squamous cell carcinoma (ESCC). In the current study, we identified CCAT2 as a relevant lncRNA and investigated its role in the progression of ESCC. RT-qPCR was adopted to detect CCAT2 expression in collected clinical samples, ESCC cell lines, and a normal cell line. We tested the correlation between CCAT2 expression and the prognosis of ESCC. RT-qPCR or immunoblotting was adopted to detect the expression of relevant factors in ESCC tissues or cells. Cell proliferation, apoptosis, migration, and invasion were examined by colony formation assay, flow cytometry, scratch assay, and Transwell assay, respectively, while subcutaneous tumorigenesis in nude mice was adopted to examine the role of CCAT2 in tumorigenesis of ESCC cells in vivo. Bioinformatics analysis, dual luciferase reporter assay, and RIP were conducted for the target relationship profiling. Me-RIP was adopted to detect m6A modification level of TK1 in ESCC tissues or cells. Upregulated CCAT2, IGF2BP2, and TK1 expression and inhibited miR-200b expression were observed in ESCC cells and tissues. CCAT2 bound to miR-200b and reduced its expression, leading to upregulated IGF2BP2 expression. IGF2BP2 improved TK1 mRNA stability to enhance its expression by recognizing its m6A modification. CCAT2 promoted the migration and invasion of ESCC cells in vitro, and tumorigenesis in vivo by upregulating TK1 expression, while overexpression of miR-200b reversed these effects of CCAT2. Overall, this study suggests that CCAT2 competitively binds to miR-200b to alleviate its inhibitory effects on IGF2BP2 expression, resulting in elevated TK1 expression, and an ensuing promotion of the development of ESCC.

scholarly journals The Clinical Significance of Aurora-A/STK15/BTAK Expression in Human Esophageal Squamous Cell Carcinoma

2005 ◽  
Vol 11 (5) ◽  
pp. 1827-1834 ◽  
Author(s):  
Eiji Tanaka ◽  
Yosuke Hashimoto ◽  
Tetsuo Ito ◽  
Tomoyuki Okumura ◽  
Takatsugu Kan ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Clinical Significance ◽  
Squamous Cell ◽  
Aurora A
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