Overexpression of lncRNA AFAP1‑AS1 promotes cell proliferation and invasion in gastric cancer

Li,Zhouxiao; Ding,Zhili; Rong,Dawei; Tang,Weiwei; Cao,Hongyong

doi:10.3892/ol.2019.10640

Overexpression of lncRNA AFAP1‑AS1 promotes cell proliferation and invasion in gastric cancer

Authors:
- Zhouxiao Li
- Zhili Ding
- Dawei Rong
- Weiwei Tang
- Hongyong Cao
View Affiliations

Affiliations: Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210001, P.R. China, Department of Plastic and Hand Surgery-Campus Innenstadt, University Hospital Munich, D‑80336 Munich, Germany
Published online on: July 22, 2019 https://doi.org/10.3892/ol.2019.10640
Pages: 3211-3217
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Long non‑coding RNA (lncRNA) actin filament‑associated protein 1 antisense RNA 1 (AFAP1‑AS1) has been revealed to be associated with certain types of cancer. However, whether the lncRNA AFAP1‑AS1 is involved in the development and progression of gastric cancer (GC) remains unknown. The present study investigated the clinical significance and biological functions of AFAP1‑AS1 in GC. The expression levels of lncRNA AFAP1‑AS1 in 52 patients with GC, and in 1 normal gastric mucosal cell line and 3 GC cell lines, were evaluated by reverse transcription quantitative polymerase chain reaction analysis. Small interfering RNAs were used to suppress AFAP1‑AS1 expression in GC cell lines. The results indicated that AFAP1‑AS1 expression levels were significantly increased in GC tissues and cell lines compared with the corresponding noncancerous tissues and normal gastric cells. In addition, the patients with GC with increased AFAP1‑AS1 expression exhibited an advanced clinical stage and an association with the occurrence of lymph node metastasis compared with those with decreased AFAP1‑AS1 expression. In vitro assays demonstrated that knockdown of AFAP1‑AS1 decreased levels of cell proliferation and migration. In addition, the results of flow cytometry demonstrated that knockdown of AFAP1‑AS1 caused cell cycle arrest. In conclusion, AFAP1‑AS1 is a novel molecule involved in GC progression, which may be a potential prognostic biomarker and target for therapeutic intervention.

View Figures

View References

1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015. View Article : Google Scholar : PubMed/NCBI
3	Yagi K, Nozawa Y, Endou S and Nakamura A: Diagnosis of early gastric cancer by magnifying endoscopy with NBI from viewpoint of histological imaging: Mucosal patterning in terms of white zone visibility and its relationship to histology. Diagn Ther Endosc. 2012:9548092012. View Article : Google Scholar : PubMed/NCBI
4	Yoon SH, Kim YH, Lee YJ, Park J, Kim JW, Lee HS and Kim B: Tumor heterogeneity in human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer assessed by CT texture analysis: Association with survival after trastuzumab treatment. PLoS One. 11:e01612782016. View Article : Google Scholar : PubMed/NCBI
5	Biffi R, Botteri E, Cenciarelli S, Luca F, Pozzi S, Valvo M, Sonzogni A, Chiappa A, Leal Ghezzi T, Rotmensz N, et al: Impact on survival of the number of lymph nodes removed in patients with node-negative gastric cancer submitted to extended lymphnode dissection. Eur J Surg Oncol. 37:305–311. 2011. View Article : Google Scholar : PubMed/NCBI
6	Yang G, Lu X and Yuan L: LncRNA: A link between RNA and cancer. Biochim Biophys Acta. 1839:1097–1109. 2014. View Article : Google Scholar : PubMed/NCBI
7	Bhan A, Soleimani M and Mandal SS: Long noncoding RNA and cancer: A new paradigm. Cancer Res. 77:3965–3981. 2017. 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	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
10	Li W, Zheng J, Deng J, You Y, Wu H, Li N, Lu J and Zhou Y: Increased levels of the long intergenic non-protein coding RNA POU3F3 promote DNA methylation in esophageal squamous cell carcinoma cells. Gastroenterology. 146:1714–1726.e5. 2014. View Article : Google Scholar : PubMed/NCBI
11	Tsang WP, Ng EK, Ng SS, Jin H, Yu J, Sung JJ and Kwok TT: Oncofetal H19-derived miR-675 regulates tumor suppressor RB in human colorectal cancer. Carcinogenesis. 31:350–358. 2010. View Article : Google Scholar : PubMed/NCBI
12	Yang SL, Lin RX, Si LH, Cui MH, Zhang XW and Fan LM: Expression and functional role of long non-coding RNA AFAP1-AS1 in ovarian cancer. Eur Rev Med Pharmacol Sci. 20:5107–5112. 2016.PubMed/NCBI
13	Ma F, Wang SH, Cai Q, Zhang MD, Yang Y and Ding J: Overexpression of LncRNA AFAP1-AS1 predicts poor prognosis and promotes cells proliferation and invasion in gallbladder cancer. Biomed Pharmacother. 84:1249–1255. 2016. View Article : Google Scholar : PubMed/NCBI
14	Luo HL, Huang MD, Guo JN, Fan RH, Xia XT, He JD and Chen XF: AFAP1-AS1 is upregulated and promotes esophageal squamous cell carcinoma cell proliferation and inhibits cell apoptosis. Cancer Med. 5:2879–2885. 2016. View Article : Google Scholar : PubMed/NCBI
15	Han X, Wang L, Ning Y, Li S and Wang Z: Long non-coding RNA AFAP1-AS1 facilitates tumor growth and promotes metastasis in colorectal cancer. Biol Res. 49:362016. View Article : Google Scholar : PubMed/NCBI
16	Fu XL, Liu DJ, Yan TT, Yang JY, Yang MW, Li J, Huo YM, Liu W, Zhang JF, Hong J, et al: Analysis of long non-coding RNA expression profiles in pancreatic ductal adenocarcinoma. Sci Rep. 6:335352016. View Article : Google Scholar : PubMed/NCBI
17	Mahul BA, Stephen B, Edge, Frederick L, et al: AJCC Cancer Staging Manual. https://cancerstaging.org/references-tools/deskreferences/pages/default.aspxSeptember 5–2018
18	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
19	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
20	Bergmann JH and Spector DL: Long non-coding RNAs: Modulators of nuclear structure and function. Curr Opin Cell Biol. 26:10–18. 2014. View Article : Google Scholar : PubMed/NCBI
21	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. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI
22	Wu L and Qu X: Cancer biomarker detection: Recent achievements and challenges. Chem Soc Rev. 44:2963–2997. 2015. View Article : Google Scholar : PubMed/NCBI
23	Armitage EG and Barbas C: Metabolomics in cancer biomarker discovery: Current trends and future perspectives. J Pharm Biomed Anal. 87:1–11. 2014. View Article : Google Scholar : PubMed/NCBI
24	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
25	Yuan Z, Xiu C, Song K, Pei R, Miao S, Mao X, Sun J and Jia S: Long non-coding RNA AFAP1-AS1/miR-320a/RBPJ axis regulates laryngeal carcinoma cell stemness and chemoresistance. J Cell Mol Med. 22:4253–4262. 2018. View Article : Google Scholar : PubMed/NCBI
26	Bo H, Gong Z, Zhang W, Li X, Zeng Y, Liao Q, Chen P, Shi L, Lian Y, Jing Y, et al: Upregulated long non-coding RNA AFAP1-AS1 expression is associated with progression and poor prognosis of nasopharyngeal carcinoma. Oncotarget. 6:20404–1829. 2015. View Article : Google Scholar : PubMed/NCBI
27	Lu X, Zhou C, Li R, Liang Z, Zhai W, Zhao L and Zhang S: Critical role for the long non-coding RNA AFAP1-AS1 in the proliferation and metastasis of hepatocellular carcinoma. Tumor Biol. 37:9699–9707. 2016. View Article : Google Scholar