AFAP1-AS1, a long noncoding RNA upregulated in lung cancer and promotes invasion and metastasis
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Long noncoding RNAs (lncRNAs) have emerged as a major regulator of cancer. Significant fraction of lncRNAs is represented on widely used microarray platforms; however, many of which have no known function. To discover novel lung cancer-related lncRNAs, we analyzed the lncRNA expression patterns in five sets of previously published lung cancer gene expression profile data that were represented on Affymetrix HG-U133 Plus 2.0 array, and identified dysregulated lncRNAs in lung cancer. One lncRNA, actin filament associated protein 1 antisense RNA1 (AFAP1-AS1), was the most significantly upregulated in lung cancer and associated with poor prognosis. In vitro experiments demonstrated that AFAP1-AS1 knockdown significantly inhibited the cell invasive and migration capability in lung cancer cells. AFAP1-AS1 knockdown also increased the expression of its antisense protein coding gene, actin filament associated protein 1 (AFAP1), and affected the expression levels of several small GTPase family members and molecules in the actin cytokeratin signaling pathway, which suggested that AFAP1-AS1 promoted cancer cell metastasis via regulation of actin filament integrity. Our findings extend the number of noncoding RNAs functionally implicated in lung cancer progression and highlight the role of AFAP1-AS1 as potential prognostic biomarker and therapeutic target of lung cancer.
KeywordsLong noncoding RNA (lncRNA) AFAP1 antisense RNA1 (AFAP1-AS1) Lung cancer Metastasis Prognosis Small GTPase
This study was supported in part by grants from the National Natural Science Foundation of China (81172189, 81272298, 81372907, 81301757, 81472531, and 81402009) and the Natural Science Foundation of Hunan Province (14JJ1010 and 2015JJ1022).
Conflicts of interest
- 5.Lu JY, Zhang M, Jin HL, Zhu JL, Wei JL, et al. Advances on molecular mechanism of chronic inflammation-driven lung cancer induced by environmental carcinogens. Prog Biochem Biophys. 2014;41:41–51.Google Scholar
- 18.Dong S, Qu X, Li W, Zhong X, Li P, et al. The long non-coding RNA, GAS5, enhances gefitinib-induced cell death in innate EGFR tyrosine kinase inhibitor-resistant lung adenocarcinoma cells with wide-type EGFR via downregulation of the IGF-1R expression. J Hematol Oncol. 2015;8:43.CrossRefPubMedPubMedCentralGoogle Scholar
- 38.Li YW, Wang YM, Zhang XY, Xue D, Kuang B, et al. Progress of long noncoding RNA HOTAIR in human cancer. Progress in Biochemistry and Biophysics. 2015;42:228–35.Google Scholar
- 39.Tang K, Wei F, Bo H, Huang HB, Zhang WL, et al. Cloning and functional characterization of a novel long non-coding RNA gene associated with hepatocellular carcinoma. Prog Biochem Biophys. 2014;41:153–62.Google Scholar
- 51.Wu W, Bhagat TD, Yang X, Song JH, Cheng Y, et al. Hypomethylation of noncoding DNA regions and overexpression of the long noncoding RNA, AFAP1-AS1, in Barrett’s esophagus and esophageal adenocarcinoma. Gastroenterology. 2013;144(956–966):e954.Google Scholar