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

Gu, Yulei; Li, Chao; Xiao, Lili; Li, Juan; Pei, Hui; Xu, Dong; Jiang, Yumin; Zhang, Xiaofan; Zhang, Luanluan; Li, Kongfei; Zhu, Zhiqiang; Chen, Xiaolong

Gu, Yulei; Li, Chao; Xiao, Lili; Li, Juan; Pei, Hui; Xu, Dong; Jiang, Yumin; Zhang, Xiaofan; Zhang, Luanluan; Li, Kongfei; Zhu, Zhiqiang; Chen, Xiaolong.

Afiliação

Gu Y; Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, Henan Province, China.
Li C; Emergency Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, Henan Province, China.
Xiao L; Department of Orthopaedic Surgery, The Affiliated Cancer Hospital of Zhengzhou University 127 Dongming Road, Zhengzhou 450008, Henan Province, China.
Li J; Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, Henan Province, China.
Pei H; Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, Henan Province, China.
Xu D; Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, Henan Province, China.
Jiang Y; Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, Henan Province, China.
Zhang X; Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, Henan Province, China.
Zhang L; Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, Henan Province, China.
Li K; Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, Henan Province, China.
Zhu Z; Department of Hematology, Yinzhou People's Hospital Affiliated to Medical College of Ningbo University Ningbo, Zhejiang Province, China.
Chen X; Emergency Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, Henan Province, China.

Am J Transl Res ; 11(9): 5438-5456, 2019.

Article em En | MEDLINE | ID: mdl-31632521

ABSTRACT

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.