Long noncoding RNA AFAP1‑AS1 is upregulated in NSCLC and associated with lymph node metastasis and poor prognosis

Leng,Xuechun; Ding,Xiangxiang; Wang,Siwei; Fang,Tian; Shen,Wenrong; Xia,Wenjia; You,Ran; Xu,Keping; Yin,Rong

doi:10.3892/ol.2018.8784

Long noncoding RNA AFAP1‑AS1 is upregulated in NSCLC and associated with lymph node metastasis and poor prognosis

Authors:
- Xuechun Leng
- Xiangxiang Ding
- Siwei Wang
- Tian Fang
- Wenrong Shen
- Wenjia Xia
- Ran You
- Keping Xu
- Rong Yin
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Affiliations: Department of Thoracic Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China, Department of Radiology, Cancer Institute of Jiangsu, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, Jiangsu 210009, P.R. China, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Department of Radiology, Cancer Institute of Jiangsu, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, Jiangsu 210009, P.R. China, Department of Comparative Medicine, Jingling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu 210002, P.R. China
Published online on: May 22, 2018 https://doi.org/10.3892/ol.2018.8784
Pages: 727-732
Copyright: © Leng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Long noncoding RNA (lncRNA) has been indicated to have an important role in various types of malignant tumors; however, only a small number of lncRNAs have been entirely elucidated. In the present study, a novel lncRNA, actin filament associated protein 1 antisense RNA 1 (AFAP1‑AS1), was investigated, which is highly expressed in non‑small cell lung cancer (NSCLC). Reverse transcription‑quantitative polymerase chain reaction and in situ hybridization were performed to detect AFAP1‑AS1 expression in frozen tissues and tissue microarrays, respectively. The results revealed that the expression level of AFAP1‑AS1 was signiﬁcantly increased in tumor tissues, compared with the paired non‑cancerous tissues. It was also determined that the AFAP1‑AS1 expression level was higher in patients with lymph node metastasis than those without lymph node metastasis (P=0.014). Kaplan‑Meier analysis was conducted to evaluate the overall survival of patients with NSCLC and different expression levels of AFAP1‑AS1, and the results indicated that patients with high AFAP1‑AS1 expression had a reduced survival time, compared with those with low AFAP1‑AS1 expression (P=0.011). Cox regression analysis was also performed to analyze the prognostic value of lncRNA AFAP1‑AS1. The obtained data demonstrated that lncRNA AFAP1‑AS1 was an unfavorable prognostic biomarker for NSCLC (HR: 3.12, 95% CI (1.05‑9.25), P=0.040). In conclusion, it was demonstrated that lncRNA AFAP1‑AS1 is overexpressed in NSCLC and an unfavorable biomarker for patients with NSCLC.

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1	Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–32. 2016. View Article : Google Scholar : PubMed/NCBI
2	Aggarwal C: Targeted therapy for lung cancer: Present and future. Ann Palliat Med. 3:229–235. 2014.PubMed/NCBI
3	Raungrut P, Wongkotsila A, Lirdprapamongkol K, Svasti J, Geater SL, Phukaoloun M, Suwiwat S and Thongsuksai P: Prognostic significance of 14–3-3γ overexpression in advanced non-small cell lung cancer. Asian Pac J Cancer Prev. 15:3513–3518. 2014. View Article : Google Scholar : PubMed/NCBI
4	Youlden DR, Cramb SM and Baade PD: The International Epidemiology of lung cancer: Geographical distribution and secular trends. J Thorac Oncol. 3:819–831. 2008. View Article : Google Scholar : PubMed/NCBI
5	Schmitt AM and Chang HY: Long noncoding RNAs in cancer pathways. Cancer Cell. 29:452–463. 2016. View Article : Google Scholar : PubMed/NCBI
6	Qiu MT, HU JW, Yin R and Xu L: Long noncoding RNA: An emerging paradigm of cancer research. Tumour Biol. 34:613–620. 2013. View Article : Google Scholar : PubMed/NCBI
7	Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL, et al: Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 464:1071–1076. 2010. View Article : Google Scholar : PubMed/NCBI
8	Esteller M: Non-coding RNAs in human disease. Nat Rev Genet. 12:861–874. 2011. View Article : Google Scholar : PubMed/NCBI
9	Mercer TR, Dinger ME and Mattick JS: Long non-coding RNAs: insights into functions. Nat Rev Genet. 10:155–159. 2009. View Article : Google Scholar : PubMed/NCBI
10	Ponting CP, Oliver PL and Reik W: Evolution and functions of long noncoding RNAs. Cell. 136:629–641. 2009. View Article : Google Scholar : PubMed/NCBI
11	Zaratiegui M, Irvine DV and Martienssen RA: Noncoding RNAs and gene silencing. Cell. 128:763–776. 2007. View Article : Google Scholar : PubMed/NCBI
12	Ono H, Motoi N, Nagano H, Miyauchi E, Ushijima M, Matsuura M, Okumura S, Nishio M, Hirose T, Inase N and Ishikawa Y: Long noncoding RNA HOTAIR is relevant to cellular proliferation, invasiveness, and clinical relapse in small-cell lung cancer. Cancer Med. 3:632–642. 2014. View Article : Google Scholar : PubMed/NCBI
13	Zhao W, An Y, Liang Y and Xie XW: Role of HOTAIR long noncoding RNA in metastatic progression of lung cancer. Eur Rev Med Pharmacol Sci. 18:1930–1936. 2014.PubMed/NCBI
14	Jeffers LK, Duan K, Ellies LG, Seaman WT, Burger-Calderon RA, Diatchenko LB and Webster-Cyriaque J: Correlation of transcription of MALAT-1, a novel noncoding RNA, with deregulated expression of tumor suppressor p53 in small DNA tumor virus models. J Cancer Ther. 4:2013. View Article : Google Scholar : PubMed/NCBI
15	Ji P, Diederichs S, Wang W, Böing S, Metzger R, Schneider PM, Tidow N, Brandt B, Buerger H, Bulk E, et al: MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene. 22:8031–8041. 2003. View Article : Google Scholar : PubMed/NCBI
16	Qiu M, Xu Y, Yang X, Wang J, Hu J, Xu L and Yin R: CCAT2 is a lung adenocarcinoma-specific long non-coding RNA and promotes invasion of non-small cell lung cancer. Tumour Biol. 35:5375–5380. 2014. View Article : Google Scholar : PubMed/NCBI
17	Qiu M, Xu Y, Wang J, Zhang E, Sun M, Zheng Y, Li M, Xia W, Feng D, Yin R and Xu L: A novel lncRNA, LUADT1, promotes lung adenocarcinoma proliferation via the epigenetic suppression of p27. Cell Death Dis. 6:e18582015. View Article : Google Scholar : PubMed/NCBI
18	Deng J, Liang Y, Liu C, He S and Wang S: The up-regulation of long non-coding RNA AFAP1-AS1 is associated with the poor prognosis of NSCLC patients. Biomed Pharmacother. 75:8–11. 2015. View Article : Google Scholar : PubMed/NCBI
19	Zeng Z, Bo H, Gong Z, et al: AFAP1-AS1, a long noncoding RNA upregulated in lung cancer and promotes invasion and metastasis. Tumour Biol. 37:729–737. 2016. View Article : Google Scholar : PubMed/NCBI
20	Zhang F, Li J, Xiao H, Zou Y, Liu Y and Huang W: AFAP1-AS1: A novel oncogenic long non-coding RNA in human cancers. Cell Prolif. 51:123972018. View Article : Google Scholar
21	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
22	VanGuilder HD, Vrana KE and Freeman WM: Twenty-five years of quantitative PCR for gene expression analysis. Biotechniques. 44:619–626. 2008. View Article : Google Scholar : PubMed/NCBI
23	Krajewska M, Krajewski S, Epstein JI, Shabaik A, Sauvageot J, Song K, Kitada S and Reed JC: Immunohistochemical analysis of bcl-2, bax, bcl-X, and mcl-1 expression in prostate cancers. Am J Pathol. 148:1567–1576. 1996.PubMed/NCBI
24	Ding Y, Shimada Y, Maeda M, Kawabe A, Kaganoi J, Komoto I, Hashimoto Y, Miyake M, Hashida H and Imamura M: Association of CC chemokine receptor 7 with lymph node metastasis of esophageal squamous cell carcinoma. Clin Cancer Res. 9:3406–3412. 2003.PubMed/NCBI
25	Wang ZY, Hu M, Dai MH, Xiong J, Zhang S, Wu HJ, Zhang SS and Gong ZJ: Upregulation of the long non-coding RNA AFAP1-AS1 affects the proliferation, invasion and survival of tongue squamous cell carcinoma via the Wnt/β-catenin signaling pathway. Mol Cancer. 17:32018. View Article : Google Scholar : PubMed/NCBI
26	Negishi M, Wongpalee SP, Sarkar S, et al: A new lncRNA, APTR, associates with and represses the CDKN1A/p21 promoter by recruiting polycomb proteins. PLoS One. 9:e952162014. View Article : Google Scholar : PubMed/NCBI
27	Yang X, Gao L, Guo X, Shi X, Wu H, Song F and Wang B: A network-based method for analysis of lncRNA-disease associations and prediction of lncRNAs implicated in diseases. PLoS One. 9:e877972014. View Article : Google Scholar : PubMed/NCBI
28	Sun W, Yang Y, Xu C and Guo J: Regulatory mechanisms of long noncoding RNAs on gene expression in cancers. Cancer Genet. 216-217:105–110. 2017. View Article : Google Scholar : PubMed/NCBI
29	Yu X and Li Z: Long non-coding RNA HOTAIR: A novel oncogene (Review). Mol Med Rep. 12:5611–5618. 2015. View Article : Google Scholar : PubMed/NCBI
30	Loewen G, Jayawickramarajah J, Zhuo Y and Shan B: Functions of lncRNA HOTAIR in lung cancer. J Hematol Oncol. 7:902014. View Article : Google Scholar : PubMed/NCBI
31	Zhang HM, Yang FQ, Chen SJ, Che J and Zheng JH: Upregulation of long non-coding RNA MALAT1 correlates with tumor progression and poor prognosis in clear cell renal cell carcinoma. Tumour Biol. 36:2947–2955. 2015. View Article : Google Scholar : PubMed/NCBI