Author:
Zhou Shuai,Qu Kang Lin,Li Jin Ang,Chen Shi Lei,Zhang Yi Gang,Zhu Chao,Jin Hao,Wang Yong,Pang Qing,Liu Hui Chun
Abstract
Abstract
Background
Cholangiocarcinoma (CCA) is one of the deadliest cancers of the digestive tract. The prognosis of CCA is poor and the 5-year survival rate is low. Bioinformatic analysis showed that early mitotic inhibitor 2 (EMI2) was overexpressed in CCA but the underlying mechanism is not known.
Methods
The data on bile duct carcinoma from TCGA and GEO databases were used to detect the expression of EMI2. The transcription factors of EMI2 were predicted using JASPAR and PROMO databases. Among the predicted transcription factors, YY1 has been rarely reported in cholangiocarcinoma, and was verified using the luciferase reporter gene assay. RT-PCR was performed to predict the downstream pathway of EMI2, and PI3K/Akt was suspected to be associated with it. Subsequently, in vivo and in vitro experiments were conducted to verify the effects of silencing and overexpressing EMI2 and YY1 on the proliferation, invasion, and metastasis of the bile duct cancer cells.
Results
EMI2 was highly expressed in CCA. Silencing EMI2 inhibited the proliferation, invasion, and migration of CCA cells, arrested cell cycle in the G1 phase, and promoted of apoptosis. The luciferase reporter gene assay showed that YY1 bound to the promoter region of EMI2, and after silencing YY1, the expression of EMI2 decreased and the progression of CCA was inhibited. Moreover, key proteins in the PI3K/Akt signaling pathway decreased after silencing EMI2.
Conclusion
EMI2 may be one of the direct targets of YY1 and promotes the progression of CCA through the PI3K/Akt signaling pathway.
Funder
the Anhui Provincial Natural Science Foundation for Outstanding Youth
the First Affiliated Hospital of Bengbu Medical College Science Fund for Distinguished Young Scholars
the 512 Talent Training Program of Bengbu Medical College
Graduate Innovation Program of Bengbu Medical College
Scientific Research Fund of Anhui Medical University
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Genetics,Oncology
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