Abstract
Cholangiocarcinoma is a relatively uncommon but highly lethal malignancy. Improving outcomes in patients depends on earlier diagnosis and appropriate treatment; however, no satisfactory diagnostic biomarkers or targeted therapies are currently available. To address this shortcoming, we analyzed the transcriptomic datasets of cholangiocarcinoma from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and found that TESC is highly expressed in cholangiocarcinoma. Elevated cellular levels of TESC are correlated with larger tumor size and predict a poor survival outcome for patients. Knockdown of TESC via RNA interference suppresses tumor growth. RNA-sequencing analysis showed that silencing of TESC decreases the level of FOXM1, leading to cell cycle arrest. Correlation analysis revealed that the cellular level of TESC is correlated with that of FOXM1 in cholangiocarcinoma patients. We further observed that upon TGF-α induction, TESC is upregulated through the EGFR-STAT3 pathway and mediates TGF-α-induced tumor cell proliferation. In vivo experiments revealed that knockdown of TESC significantly attenuates tumor cell growth. Therefore, our data provide novel insight into TESC-mediated oncogenesis and reveal that TESC is a potential biomarker or serves as a therapeutic target for cholangiocarcinoma.
Highlights
Cholangiocarcinoma, which is a rare malignant tumor, arises from biliary epithelial cells in the biliary tree
To identify the potential genes involved in tumorigenesis and predict poor survival in cholangiocarcinoma, we analyzed the gene expression profiling datasets of cholangiocarcinoma from the The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO; GSE76297 and GSE57555)
We demonstrated that TESC promotes cholangiocarcinoma tumor cell growth in vitro and in vivo
Summary
Cholangiocarcinoma, which is a rare malignant tumor, arises from biliary epithelial cells in the biliary tree. Radical surgical resection is an acceptable form of curative treatment. The incidence of cholangiocarcinoma has rapidly increased globally [5], necessitating the development of strategies for early diagnosis and effective treatment. TESC, known as tescalcin or calcineurin B homologous protein 3 (CHP3), was originally discovered during an analysis of embryonic mouse testis and contains an EF-hand motif that is characteristic of a large family of Ca2+ -binding proteins, the members of which play critical roles in several cellular processes [6]. Several recent reports demonstrated that overproduction of cellular TESC is linked to tumor progression of several types of cancer, including radiation-induced papillary thyroid carcinoma, acute myeloid leukemia, renal cell carcinoma, and human colorectal cancer [10,11,12,13,14]
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