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Biomed Pharmacother. 2017 Dec;96:877-883. doi: 10.1016/j.biopha.2017.10.033. Epub 2017 Nov 6.

Long noncoding RNA HNF1A-AS1 indicates a poor prognosis of colorectal cancer and promotes carcinogenesis via activation of the Wnt/β-catenin signaling pathway.

Author information

1
Department of Internal Medicine, Xi'an Central Hospital, Shaanxi Province, China.
2
General Surgery, Ankang Central Hospital, Shaanxi Province, China.
3
Department of Gastroenterology, the Second Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, China.
4
Department of Neurology, the Second Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, China. Electronic address: bianying3260@126.com.
5
Department of General Surgery, The First People's Hospital of Xianyang City, China. Electronic address: chenyanhui1967@163.com.
6
Department of Gastroenterology, the Second Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, China. Electronic address: zhangfengli197902@163.com.

Abstract

Long non-coding RNAs (lncRNAs) have been identified to play critical roles in tumorigenesis. LncRNA HNF1A-AS1 has been suggested to act as an oncogene and serves as a novel prognostic biomarker for various cancer. However, the biological role and clinical significance of lncRNA HNF1A-AS1 in colorectal cancer (CRC) have yet to be fully elusive. Therefore, the present study was designed to determine the expression of lncRNA HNF1A-AS1 in patients with CRC, the role of lncRNA HNF1A-AS1 in CRC cells, as well as the underlying regulatory mechanisms. Our results indicated that the expression of lncRNA HNF1A-AS1 was significantly upregulated in both CRC tumor tissues and CRC cell lines in comparison with adjacent non-tumor tissues and the human normal colonic epithelial cell line (HcoEpiC). The Kaplan-Meier survival analysis further suggested that high expression of lncRNA HNF1A-AS1 might be an independent prognostic factor for disease-free survival (DFS) and overall survival (OS) in patients with CRC. Moreover, the area under the receiver operating characteristic (ROC) curve for HNF1A-AS1 was up to 0.8714, implying that HNF1A-AS1 had diagnostic significance as it could discriminate tumor tissues from nontumorous tissues. In addition, silencing of lncRNA HNF1A-AS1 abrogated the proliferation of CRC cells by MTS assay and clonogenic assay, arrested cell cycle at G0/G1 stage and reduced the migration and invasion in CRC cells. Finally, we found that decreased expression of lncRNA HNF1A-AS1 suppressed the Wnt/β-catenin signaling pathway activity by downregulating the expression of β-catenin,cyclinD1, and c-myc. In conclusion, these findings provide evidence that lncRNA HNF1A-AS1 may be considered as a new prognostic biomarker and therapeutic target in patients with CRC.

KEYWORDS:

Colorectal cancer; HNF1A-AS1; Wnt/β-catenin signaling pathway; lncRNA

PMID:
29145164
DOI:
10.1016/j.biopha.2017.10.033
[Indexed for MEDLINE]

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