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Research Paper|Volume 10, Issue 11|pp 3371—3381

LncRNA CDKN2BAS predicts poor prognosis in patients with hepatocellular carcinoma and promotes metastasis via the miR-153-5p/ARHGAP18 signaling axis

Junzheng Chen1, Xitian Huang2, Weijun Wang3, Hongcheng Xie2, Jianfeng Li1, Zhenfen Hu1, Zhijian Zheng1, Huiyong Li1, Lingfang Teng1
  • 1Surgical Center, The Affiliated Wenling Hospital of Wenzhou Medical University, Wenling 317500, Zhejiang Province, China
  • 2Department of Hepatology, The Affiliated Wenling Hospital of Wenzhou Medical University, Wenling 317500, Zhejiang Province, China
  • 3Department of Hepatobiliary Surgery, Sanxinmeide Geriatrics Hospital of Wenling, Wenling 317500, Zhejiang Province, China

* * Equal contribution

Received: August 23, 2018Accepted: November 4, 2018Published: November 29, 2018
https://doi.org/10.18632/aging.101645

Copyright: © 2018 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Growing evidence shows that long noncoding RNAs (lncRNAs) play a crucial role in cancer progression. However, whether lncRNA CDKN2BAS is involved in human hepatocellular carcinoma (HCC) metastasis remains unclear.

Methods: Human lncRNA microarray analysis was performed to detect differential expression levels of lncRNAs in metastatic HCC tissues. Effects of CDKN2BAS on cell proliferation, migration, and apoptosis were determined by MTT assay, colony formation assay, migration assay, scratch assay, and flow cytometry. The xenograft experiment was used to confirm the effect of CDKN2BAS on HCC in vivo. qRT-PCR and Western blot were performed to determine the expression levels of mRNAs and proteins. Luciferase reporter assay was used to identify the specific target relationships.

Results: CDKN2BAS was remarkably up-regulated in metastatic HCC tissues compared with the adjacent non-tumor tissues. CDKN2BAS promotes HCC cell growth and migration in vitro and in vivo. Additionally, CDKN2BAS upregulated the expression of Rho GTPase activating protein 18 (ARHGAP18) by sponging microRNA-153-5p (miR-153-5p), and thus promoted HCC cell migration. Besides, CDKN2BAS downregulated the expression of Krüppel-like factor 13 (KLF13) and activated MEK-ERK1/2 signaling, thus reducing apoptosis in HCC cells.

Conclusions: Our study revealed that lncRNA CDKN2BAS promotes HCC metastasis by regulating the miR-153-5p/ARHGAP18 signaling.