Oncotarget

Research Papers:

Upregulated NNT-AS1, a long noncoding RNA, contributes to proliferation and migration of colorectal cancer cells in vitro and in vivo

Qian Wang _, Lei Yang, Xin Hu, Yuliang Jiang, Yizhang Hu, Zhe Liu, Jian Liu, Tao Wen, Yingmin Ma, Guangyu An and Guosheng Feng

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Oncotarget. 2017; 8:3441-3453. https://doi.org/10.18632/oncotarget.13840

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Abstract

Qian Wang1, Lei Yang3, Xin Hu1, Yuliang Jiang1, Yizhang Hu1, Zhe Liu1, Jian Liu3, Tao Wen3, Yingmin Ma2, Guangyu An1, Guosheng Feng1

1Department of Oncology, Affiliated Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China

2Department of Respiratory Medicine, Affiliated Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China

3Medical Research Center, Affiliated Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China

Correspondence to:

Guosheng Feng, email: [email protected]

Guangyu An, email: [email protected]

Yingmin Ma, email: [email protected]

Keywords: long non-coding RNA, NNT-AS1, colorectal cancer, MAPK/Erk, biomarker

Received: April 17, 2016    Accepted: November 21, 2016    Published: December 09, 2016

ABSTRACT

The expression patterns of the long non-coding RNA Nicotinamide Nucleotide Transhydrogenase-antisense RNA1 (NNT-AS1) have not been investigated in the context of cancer. In this study, we aim to investigate the NNT-AS1 expression level in colorectal cancer (CRC) patients and its potential roles in tumor biology. We measured the expression of NNT-AS1 in 70 paired tumor tissues and adjacent normal tissues. NNT-AS1 was expressed higher in tumor tissues than that in adjacent noncancer tissues, and higher expression of NNT-AS1 was significantly correlated with lymph node metastasis (Yes vs. No, P=0.004), TNM stage (I/II vs. III/IV, P=0.004), vessel invasion (Yes vs. No, P=0.002) and differentiation (well and moderate vs. poor, P=0.008). Multivariate analyses revealed that NNT-AS1 expression was an independent predictor of overall survival (P=0.0174) and progression free survival (P=0.0132) for CRC. Knockdown of NNT-AS1 using small interfering RNA (siRNA) significantly impaired CRC cell proliferation, migration and invasion in vitro and silencing NNT-AS1 also suppressed tumor growth and metastasis in nude mice. The western blot experiments revealed that silencing NNT-AS1 inhibited epithelial-mesenchymal transition (EMT) and inactivated MAPK/Erk signaling pathway in CRC cell lines. In conclusion, our studies implied that NNT-AS1 may involve in the development and progression of CRC via its regulation of cell proliferation, migration, and invasion by NNT-AS1-mediated activating of MAPK/Erk signaling pathway and EMT. NNT-AS1 may be a useful diagnostic and prognostic biomarker and a potential therapeutic target in CRC patients.


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