OTUB2通过调控YAP1/TAZ促进食管鳞状细胞癌进展。
OTUB2 Regulates YAP1/TAZ to Promotes the Progression of Esophageal Squamous Cell Carcinoma.
作者信息
Liu Li, Cheng Hu, Ji Min, Su Liping, Lu Ziyang, Hu Xiayun, Guan Yaling, Xiao Jinling, Ma Lijuan, Zhang Wei, Pu Hongwei
机构信息
Department of Pathology, First Affliated Hospital, Xinjiang Medical University, No. 137, Liyushan South Road, Urumqi, 830054, Xinjiang, China.
Department of Anesthesiology, First Affliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, People's Republic of China.
出版信息
Biol Proced Online. 2022 Jul 18;24(1):10. doi: 10.1186/s12575-022-00169-9.
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.
目的
通过干扰Otubain-2（OTUB2）表达，研究其对食管鳞状细胞癌（ESCC）增殖、侵袭和迁移的影响。
方法
采用生物信息学分析方法分析OTUB2在食管癌中的表达以及OTUB2与YAP1/TAZ之间的相互作用。选取183例石蜡包埋的ESCC组织进行免疫组织化学染色，检测OTUB2、YAP1、TAZ、CTGF及其与临床病理参数的关系，进而分析ESCC患者的生存预后。采用免疫荧光、蛋白质印迹法和qRT-PCR评估ESCC细胞系中的OTUB2。将OTUB2表达最高的细胞系用慢病毒转染以降低OTUB2水平。使用CCK-8、伤口愈合和克隆形成试验检测KYSE150细胞增殖、迁移和侵袭的变化。Transwell试验和流式细胞术鉴定OTUB2靶点，并探索其在ESCC中的作用和机制。同时观察OTUB2对YAP1/TAZ信号通路的影响。
结果
生物信息学分析显示OTUB2在食管癌中高表达，且与YAP1/TAZ相关。免疫组织化学显示，与癌旁组织相比，ESCC样本中OTUB2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敲低后KYSE150细胞的增殖、迁移和侵袭能力显著降低（P < 0.05）。敲低OTUB2表达后，YAP1、TAZ和CTGF的蛋白表达水平降低（P < 0.05）。ESCC细胞系中OTUB2敲低抑制了YAP1/TAZ信号通路。
结论
OTUB2调节YAP1/TAZ的蛋白表达，促进细胞增殖、迁移、侵袭和肿瘤发展。因此，OTUB2可能是ESCC的生物标志物和ESCC治疗的潜在靶点。
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