OTUB2 Regulates YAP1/TAZ to Promotes the Progression of Esophageal Squamous Cell Carcinoma.

IF 4.3 3区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS
Li Liu, Hu Cheng, Min Ji, Liping Su, Ziyang Lu, Xiayun Hu, Yaling Guan, Jinling Xiao, Lijuan Ma, Wei Zhang, Hongwei Pu
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引用次数: 0

Abstract

Objective: The effects of Otubain-2 (OTUB2) on the proliferation, invasion, and migration of esophageal squamous cell carcinoma (ESCC) were investigated by interfering with OTUB2 expression.

Methods: Bioinformatics analysis was used to analyze OTUB2 expression in esophageal carcinoma and interactions between OTUB2 and YAP1/TAZ. Paraffin-embedded ESCC tissues (n = 183) were selected for immunohistochemical staining to detect OTUB2, YAP1, TAZ, CTGF and their relationship with clinicopathological parameters, then the survival prognosis of ESCC patients was analyzed. Immunofluorescence, western blotting, and qRT-PCR were used to evaluate OTUB2 in ESCC cell lines. Cell lines with the highest expression of OTUB2 were transfected with lentivirus to knockdown OTUB2 levels. Changes in KYSE150 cell proliferation, migration, and invasion were measured using CCK-8, wound healing, and clone formation assays. The Transwell test and flow cytometry identified OTUB2 targets and explored roles and mechanisms involved in ESCC. Effects of OTUB2 on YAP1/TAZ signaling were also observed.

Results: Bioinformatics analysis revealed OTUB2 was highly expressed in esophageal cancer and was associated with YAP1/TAZ. Immunohistochemistry showed that OTUB2 expression was increased in ESCC samples compared to parcancerous tissue. YAP1 and TAZ were higher expression in ESCC tissues, mainly localized in the nucleus. Compared with controls, the proliferation, migration, and invasion ability of KYSE150 cells after OTUB2 knockdown were significantly reduced (P < 0.05). The protein expression levels of YAP1, TAZ and CTGF decreased after knocking down the expression of OTUB2 (P < 0.05). OTUB2 knockdown in ESCC cell lines suppressed YAP1/TAZ signaling.

Conclusions: OTUB2 regulated the protein expression of YAP1/TAZ to promote cell proliferation, migration, invasion, and tumor development. Therefore, OTUB2 may represent a biomarker for ESCC and a potential target for ESCC treatment.

Abstract Image

Abstract Image

Abstract Image

OTUB2调控YAP1/TAZ促进食管鳞状细胞癌进展
目的:通过干扰OTUB2的表达,探讨otubain2 (OTUB2)对食管鳞状细胞癌(ESCC)增殖、侵袭和迁移的影响。方法:应用生物信息学分析OTUB2在食管癌组织中的表达及OTUB2与YAP1/TAZ的相互作用。选择石蜡包埋的ESCC组织(n = 183)进行免疫组化染色,检测OTUB2、YAP1、TAZ、CTGF及其与临床病理参数的关系,分析ESCC患者的生存预后。采用免疫荧光、western blotting和qRT-PCR对ESCC细胞株中的OTUB2进行检测。用慢病毒转染OTUB2最高表达的细胞系,降低OTUB2水平。使用CCK-8、伤口愈合和克隆形成试验测量KYSE150细胞增殖、迁移和侵袭的变化。Transwell试验和流式细胞术确定了OTUB2靶点,并探讨了其在ESCC中的作用和机制。OTUB2对YAP1/TAZ信号的影响也被观察到。结果:生物信息学分析显示OTUB2在食管癌中高表达,并与YAP1/TAZ相关。免疫组化显示,与癌旁组织相比,OTUB2在ESCC中表达增加。YAP1和TAZ在ESCC组织中表达较高,主要定位于细胞核。与对照组相比,OTUB2敲除后KYSE150细胞的增殖、迁移和侵袭能力显著降低(P)。结论:OTUB2调节YAP1/TAZ蛋白表达,促进细胞增殖、迁移、侵袭和肿瘤发生。因此,OTUB2可能代表ESCC的生物标志物和ESCC治疗的潜在靶点。
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来源期刊
Biological Procedures Online
Biological Procedures Online 生物-生化研究方法
CiteScore
10.50
自引率
0.00%
发文量
16
审稿时长
>12 weeks
期刊介绍: iological Procedures Online publishes articles that improve access to techniques and methods in the medical and biological sciences. We are also interested in short but important research discoveries, such as new animal disease models. Topics of interest include, but are not limited to: Reports of new research techniques and applications of existing techniques Technical analyses of research techniques and published reports Validity analyses of research methods and approaches to judging the validity of research reports Application of common research methods Reviews of existing techniques Novel/important product information Biological Procedures Online places emphasis on multidisciplinary approaches that integrate methodologies from medicine, biology, chemistry, imaging, engineering, bioinformatics, computer science, and systems analysis.
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