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Toxicol Appl Pharmacol. 2015 Jun 1;285(2):79-88. doi: 10.1016/j.taap.2015.04.003. Epub 2015 Apr 15.

A novel long noncoding RNA AK001796 acts as an oncogene and is involved in cell growth inhibition by resveratrol in lung cancer.

Author information

1
Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou 510182, PR China.
2
Department of Thoracic Surgery, General Hospital of Guangzhou Military Command of Chinese People's Liberation Army, Guangzhou 510010, PR China.
3
Department of Pathology, Guangzhou Medical University, Guangzhou 510182, PR China.
4
Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou 510182, PR China. Electronic address: jiangyiguo@vip.163.com.

Abstract

Lung cancer is the most common form of cancer throughout the world. The specific targeting of long noncoding RNAs (lncRNAs) by resveratrol opened a new avenue for cancer chemoprevention. In this study, we found that 21 lncRNAs were upregulated and 19 lncRNAs were downregulated in lung cancer A549 cells with 25 μmol/L resveratrol treatment determined by microarray analysis. AK001796, the lncRNA with the most clearly altered expression, was overexpressed in lung cancer tissues and cell lines, but its expression was downregulated in resveratrol-treated lung cancer cells. By monitoring cell proliferation and growth in vitro and tumor growth in vivo, we observed a significant reduction in cell viability in lung cancer cells and a slow growth in the tumorigenesis following AK001796 knockdown. We also found that AK001796 knockdown caused a cell-cycle arrest, with significant increases in the percentage of cells in G0/G1 in lung cancer cells. By using cell cycle pathway-specific PCR arrays, we detected changes in a number of cell cycle-related genes related to lncRNA AK001796 knockdown. We further investigated whether AK001796 participated in the anticancer effect of resveratrol and the results showed that reduced lncRNA AK001796 level potentially impaired the inhibitory effect of resveratrol on cell proliferation. To our knowledge, this is the first study to report the changes in an lncRNA expression profile induced by resveratrol in lung cancer.

KEYWORDS:

AK001796; Cancer chemoprevention; Long noncoding RNA; Lung cancer; Lung carcinogenesis; Resveratrol

PMID:
25888808
DOI:
10.1016/j.taap.2015.04.003
[Indexed for MEDLINE]

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