Wnt信号通路
癌症研究
结直肠癌
癌变
基因沉默
癌基因
长非编码RNA
生物
细胞周期
HNF1A型
癌症
细胞生长
信号转导
基因敲除
连环素
细胞生物学
下调和上调
细胞周期蛋白D1
基因
遗传学
作者
Xin Zhang,Yumin Xiong,Fengying Tang,Ying Bian,Yanhui Chen,Fengli Zhang
标识
DOI:10.1016/j.biopha.2017.10.033
摘要
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.
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