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

Li Liu; Hu Cheng; Min Ji; Liping Su; Ziyang Lu; Xiayun Hu; Yaling Guan; Jinling Xiao; Lijuan Ma; Wei Zhang; Hongwei Pu

doi:10.1186/s12575-022-00169-9

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

Biol Proced Online. 2022 Jul 18;24(1):10. doi: 10.1186/s12575-022-00169-9.

Authors

Li Liu^#¹, Hu Cheng^#², Min Ji³, Liping Su¹, Ziyang Lu⁴, Xiayun Hu⁵, Yaling Guan³, Jinling Xiao³, Lijuan Ma³, Wei Zhang⁶, Hongwei Pu⁷

Affiliations

¹ Department of Pathology, First Affliated Hospital, Xinjiang Medical University, No. 137, Liyushan South Road, Urumqi, 830054, Xinjiang, China.
² Department of Anesthesiology, First Affliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, People's Republic of China.
³ School of Basic Medicine, Xinjiang Medical University, Urumqi, Xinjiang, People's Republic of China.
⁴ Qilu Hospital, Jinan, Shandong Province, China.
⁵ Shanghai Changhai Hospital, Shanghai, China.
⁶ Department of Pathology, First Affliated Hospital, Xinjiang Medical University, No. 137, Liyushan South Road, Urumqi, 830054, Xinjiang, China. zwyhr100@163.com.
⁷ Department of Discipline Construction, First Affliated Hospital, Xinjiang Medical University, No. 137, Liyushan South Road, Urumqi, 830054, Xinjiang, China. 576250630@qq.com.

^# Contributed equally.

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.

Keywords: Biomarker; Esophageal squamous cell carcinoma; OTUB2; TAZ; YAP1.

Abstract

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