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High expression of long non-coding RNA NNT-AS1 facilitates progression of cholangiocarcinoma through promoting epithelial-mesenchymal transition.

ABSTRACT: BACKGROUND:Cholangiocarcinoma (CCA) is a biliary malignancy, which is notoriously difficult to diagnose and associated with poor survival. Accumulating evidence indicates that long non-coding RNA Nicotinamide Nucleotide Transhydrogenase-antisense RNA1 (NNT-AS1) is overexpressed in several tumors and plays a crucial role in the development of neoplasm. However, the expression pattern and functional role of NNT-AS1 in CCA remain largely unknown. METHODS:NNT-AS1 expression was assessed by RT-qPCR and In Situ Hybridization (ISH) assay. The clinical relevance of NNT-AS1 was analyzed using a CCA tissue microarray with follow-up data. The function role of NNT-AS1 and its underlying molecular mechanisms were evaluated using both in vitro/in vivo experiments and bioinformatics analysis. Luciferase reporter assay, western blot and RT-qPCR were conducted to identify the miRNA/target gene involved in the regulation of CCA progression. RESULTS:LncRNA NNT-AS1 was found highly expressed in CCA. Upregulated NNT-AS1 expression was tightly associated with clinical malignancies and predicted poor prognosis of CCA patients. Functional studies showed that NNT-AS1 knockdown inhibited cell proliferation, migration and invasion of CCA cells in vitro. Conversely, NNT-AS1 overexpression showed the opposite biological effects. In a tumor xenograft model, we confirmed that NNT-AS1 knockdown could significantly inhibit the growth of CCA, while NNT-AS1 overexpression promoted CCA development. Mechanistically, we demonstrated that NNT-AS1 might function as a ceRNA in regulating HMGA2 (high mobility group AT-hook 2) through competitively binding to miR-142-5p in CCA. Moreover, we showed that NNT-AS1 regulated epithelial-mesenchymal transition in CCA. CONCLUSION:In summary, these findings suggest the potential prognostic and therapeutic value of NNT-AS1/miR-142-5p/HMGA2 axis in CCA patients.

SUBMITTER: Gu Y

PROVIDER: S-EPMC6789241 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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High expression of long non-coding RNA NNT-AS1 facilitates progression of cholangiocarcinoma through promoting epithelial-mesenchymal transition.

Gu Yulei Y Li Chao C Xiao Lili L Li Juan J Pei Hui H Xu Dong D Jiang Yumin Y Zhang Xiaofan X Zhang Luanluan L Li Kongfei K Zhu Zhiqiang Z Chen Xiaolong X

American journal of translational research 20190915 9

<h4>Background</h4>Cholangiocarcinoma (CCA) is a biliary malignancy, which is notoriously difficult to diagnose and associated with poor survival. Accumulating evidence indicates that long non-coding RNA Nicotinamide Nucleotide Transhydrogenase-antisense RNA1 (NNT-AS1) is overexpressed in several tumors and plays a crucial role in the development of neoplasm. However, the expression pattern and functional role of NNT-AS1 in CCA remain largely unknown.<h4>Methods</h4>NNT-AS1 expression was assess ...[more]

PMID: 31632521

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Dataset Information

High expression of long non-coding RNA NNT-AS1 facilitates progression of cholangiocarcinoma through promoting epithelial-mesenchymal transition.

Publications

High expression of long non-coding RNA NNT-AS1 facilitates progression of cholangiocarcinoma through promoting epithelial-mesenchymal transition.

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