Abstract
BackgroundCholangiocarcinoma (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.MethodsThe 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.ResultsEMI2 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.ConclusionEMI2 may be one of the direct targets of YY1 and promotes the progression of CCA through the PI3K/Akt signaling pathway.
Highlights
Due to the increase in incidence, more and more researchers have focused their efforts on understanding cholangiocarcinoma (CCA)
We found that YIN-YANG 1 (YY1) is a transcription factor of early mitotic inhibitor 2 (EMI2)
EMI2 was overexpressed in CCAWe combined the The Cancer Genome Atlas (TCGA) database with GSE3325 and GSE22633 datasets from GEO to search for differentially expressed genes, among which TCGA showed 4393 upregulated genes, GSE3325 showed 2460 upregulated genes, and GSE22633 showed 499 up-regulated genes (Additional file 2: Fig. S1A, B)
Summary
Due to the increase in incidence, more and more researchers have focused their efforts on understanding cholangiocarcinoma (CCA). The study of new prognostic targets is crucial to understand the molecular mechanism of CCA. EMI2 is an inhibitor of ubiquitin ligase and is involved in inhibiting the formation of late complex/cyclosome (APC/C) [7]. The C-terminal region competitively binds APC/C with cyclin B, and there is a zinc-binding region at the C-terminal, which inhibits APC/C ubiquitin ligase activity [11]. Studies have reported that EMI2 is overexpressed in hepatocellular carcinoma and associated with a poor prognosis [12]. The prognosis is poor in breast cancer patients with a high expression of EMI2 [13]. 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
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
