RNF6 activates TGF-β1/c-Myb pathway to promote EMT in esophageal squamous cell carcinoma

Jingge Cheng; Kun Wu; Qian Yang; Ziming Zhu; Hongye Zhao

doi:10.3389/fonc.2023.1081333

RNF6 activates TGF-β1/c-Myb pathway to promote EMT in esophageal squamous cell carcinoma

Front Oncol. 2023 Feb 9:13:1081333. doi: 10.3389/fonc.2023.1081333. eCollection 2023.

Authors

Jingge Cheng¹, Kun Wu², Qian Yang³, Ziming Zhu⁴, Hongye Zhao⁵

Affiliations

¹ The Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
² The Department of Anesthesiology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
³ The Department of Thoracic Surgery, Han Dan Central Hospital, Handan, China.
⁴ The Department of Thoracic Surgery, The First Hospital of Xingtai, Xingtai, China.
⁵ The Department of Dermatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

Abstract

Objective: This study aimed to investigate RING-Finger Protein 6 (RNF6) expression in esophageal squamous cell carcinoma (ESCC) cells and whether it affects cell proliferation, invasion, and migration by regulating the TGF-β1/c-Myb pathway.

Methods: TCGA database was used to analyze RNF6 expression in normal tissues and esophageal cancer tissues. Kaplan-Meier method was used to examine the correlation between RNF6 expression and patient prognosis. SiRNA interference vector and RNF6 overexpression plasmid were constructed, and RNF6 was transfected into Eca-109 and KYSE-150 esophageal cancer cell line. In vitro scratch assay and Transwell assay were conducted to investigate the effects of RNF6 on the migration and invasion of Eca-109 and KYSE-150 cells. RT-PCR detected the expression of Snail, E-cadherin, and N-cadherin, and TUNEL detected the apoptosis of cells.

Results: RNF6 up-regulation promoted the progression of esophageal cancer and predicted poor prognosis. RNF6 also enhanced the migration and invasion of ESCC cells in vitro. RNF6 silencing inhibited the migration and invasion of ESCC cells. TGF-β inhibitors reversed the oncogenic effects of RNF6. RNF6 regulated the migration and invasion of ESCC cells by activating the TGF-β pathway. RNF6/TGF-β1 promoted esophageal cancer progression through c-Myb.

Conclusion: RNF6 promotes the proliferation, invasion, and migration of ESCC cells possibly by activating the TGF-β1/c-Myb pathway and affects the progression of ESCC.

Keywords: RNF6; TGF-β1 signaling pathway; esophageal squamous cell carcinoma; invasion; proliferation.