Abstract
BackgroundCholangiocarcinoma (CCA) is a mortal cancer with high mortality, whereas the function and mechanism of occurrence and progression of CCA are still mysterious. Long non-coding RNAs (lncRNAs) could function as important regulators in carcinogenesis and cancer progression. Growing evidences have indicated that the novel lncRNA linc00473 plays an important role in cancer progression and metastasis. However, its function and molecular mechanism in CCA remain unknown.MethodsThe linc00473 expression in CCA tissues and cell lines was analyzed using qRT-PCR. Gain- and loss-of-function experiments were conducted to investigate the biological functions of linc00473 both in vitro and in vivo. Insights into the underlying mechanisms of competitive endogenous RNAs (ceRNAs) were determined by bioinformatics analysis, dual-luciferase reporter assays, qRT-PCR arrays, RNA immunoprecipitation (RIP) and rescue experiments.ResultsLinc00473 was highly expressed in CCA tissues and cell lines. Linc00473 knockdown inhibited CCA growth and metastasis. Furthermore, linc00473 acted as miR-506 sponge and regulated its target gene DDX5 expression. Rescue assays verified that linc00473 modulated the tumorigenesis of CCA by regulating miR-506.ConclusionsThe data indicated that linc00473 played an oncogenic role in CCA growth and metastasis, and could serve as a novel molecular target for treating CCA.
Highlights
Cholangiocarcinoma (CCA) is a mortal cancer with high mortality, whereas the function and mechanism of occurrence and progression of CCA are still mysterious
LncRNA ZFAS1 displays oncogenic properties and regulates important processes associated with EMT in head and neck squamous cell carcinoma [6], Long non-coding RNAs (lncRNAs) PVT1 acts as an oncogenic gene and plays an important role in radio sensitivity in malignant nasopharyngeal carcinoma via activating the KAT2A acetyltransferase and stabilizing HIF-1α [7]. lncRNA DANCR regulates proliferation and migration by epigenetically silencing FBP1 in tumorigenesis of CCA [8]
Linc00473 was up‐regulated in cholangiocarcinoma tissues and cells To identify differentially expressed lncRNAs in CCA, our group downloaded and analyzed cholangiocarcinoma RNA sequencing (RNA-seq) datasets from The Cancer Genome Atlas (TCGA)
Summary
Cholangiocarcinoma (CCA) is a mortal cancer with high mortality, whereas the function and mechanism of occurrence and progression of CCA are still mysterious. Long non-coding RNAs (lncRNAs) could function as important regulators in carcinogenesis and cancer progression. Growing evidences have indicated that the novel lncRNA linc00473 plays an important role in cancer progression and metastasis. Increasing evidence shows that lncRNAs are important regulatory factors of gene expression and involved in various physiological. LncRNA ZFAS1 displays oncogenic properties and regulates important processes associated with EMT in head and neck squamous cell carcinoma [6], lncRNA PVT1 acts as an oncogenic gene and plays an important role in radio sensitivity in malignant nasopharyngeal carcinoma via activating the KAT2A acetyltransferase and stabilizing HIF-1α [7]. Mounting evidence illuminates that the exploration of molecular alteration in CCA would help improve our understanding of the progression and find out potential therapeutic targets
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