Foundation of ceRNA networks and functional validation of AFAP1-AS1 in lung adenocarcinoma_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

WANG Huixin ¹ , LI Qian ¹ , HOU Xiaowen ¹ , SHI Xinzhu ² ,  FENG Xu ¹

1. Statistics Teaching and Research Office of the School of Public Health, Shenyang Medical College, Shenyang, 110034, P. R. China;
2. Epidemiology Teaching and Research Office of the School of Public Health, Shenyang Medical College, Shenyang, 110034, P. R. China;

Corresponding author：

FENG Xu, Email: fxsymc@163.com

Keywords：

Bioinformatics; lung adenocarcinoma; competing endogenous RNA; long non-coding RNA; AFAP1-AS1

DOI：

10.7507/1007-4848.202207067

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective A competing endogenous RNA (ceRNA) regulatory network associated with long non-coding RNA (lncRNA) specific for lung adenocarcinoma (LUAD) was constructed based on bioinformatics methods, and the functional mechanism of actinfilament-associated protein 1-antisense RNA1 (AFAP1-AS1) in LUAD was analyzed, in order to provide a new direction for the study of LUAD therapeutic targets. Methods The gene chip of LUAD was downloaded from the Gene Expression Omnibus (GEO), and lncRNA and mRNA with differential expression between LUAD and normal tissues were screened using GEO2R online software, and their target genes were predicted by online databases to construct ceRNA networks and perform enrichment analysis. In cell experiments, AFAP1-AS1 was genetically knocked down and siRNA was constructed and transfected into LUAD cells A549 by cell transfection. CCK8, transwell, scratch assay and flow cytometry were used to detect the ability of cells to proliferate, invade, migrate and apoptosis. Results A total of 6 differentially expressed lncRNA and 494 differentially expressed mRNA were identified in the microarray of LUAD. The ceRNA network involved a total of 6 lncRNA, 22 miRNA, and 55 mRNA. Enrichment analysis revealed that mRNA was associated with cancer-related pathways. In cell assays, knockdown of AFAP1-AS1 inhibited cell proliferation, invasion, and migration, and AFAP1-AS1 promoted apoptosis. Conclusion In this study, we construct a lncRNA-mediated ceRNA network, which may help to further investigate the mechanism of action of LUAD. In addition, through cellular experiments, AFAP1-AS1 is found to have potential as a therapeutic target for LUAD.

Citation： WANG Huixin, LI Qian, HOU Xiaowen, SHI Xinzhu, FENG Xu. Foundation of ceRNA networks and functional validation of AFAP1-AS1 in lung adenocarcinoma. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2024, 31(4): 576-584. doi: 10.7507/1007-4848.202207067 Copy

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17.	Han M, Gu Y, Lu P, et al. Exosome-mediated lncRNA AFAP1-AS1 promotes trastuzumab resistance through binding with AUF1 and activating ERBB2 translation. Mol Cancer, 2020, 19(1): 26.
18.	Zhou Y, Shi X, Chen H, et al. Tumor immune microenvironment characterization of primary lung adenocarcinoma and lymph node metastases. Biomed Res Int, 2021, 2021: 5557649.
19.	Dang Y, Ouyang X, Ren W, et al. LncRNA AFAP1-AS1 modulates the proliferation and invasion of gastric cancer cells by regulating AFAP1 via miR-205-5p. Cancer Manag Res, 2021, 13: 5163-5175.
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22.	Sun J, Min H, Yu L, et al. The knockdown of LncRNA AFAP1-AS1 suppressed cell proliferation, migration, and invasion, and promoted apoptosis by regulating miR-545-3p/hepatoma-derived growth factor axis in lung cancer. Anticancer Drugs, 2021, 32(1): 11-21.

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin, 2019, 69(1): 7-34.
2. Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization classification of lung tumors: Impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol, 2015, 10(9): 1243-1260.
3. Bridges MC, Daulagala AC, Kourtidis A. LNCcation: lncRNA localization and function. J Cell Biol, 2021, 220(2): e202009045.
4. Hou G, Yang J, Tang J, et al. LncRNA GAS6-AS2 promotes non-small-cell lung cancer cell proliferation via regulating miR-144-3p/ MAPK6 axis. Cell Cycle, 2021, 20(2): 179-193.
5. Huang Z, Zhuo W, Xu R, et al. The relationship between long noncoding RNA (lncRNA) small nucleolar RNA host gene 12 (SNHG12) expression in solid malignant tumors and prognosis of tumor patients: A systematic review and meta-analysis. Medicine (Baltimore), 2020, 99(41): e22247.
6. Rajagopal T, Talluri S, Akshaya RL, et al. HOTAIR LncRNA: A novel oncogenic propellant in human cancer. Clin Chim Acta, 2020, 503: 1-18.
7. Kopp F, Mendell JT. Functional classification and experimental dissection of long noncoding RNAs. Cell, 2018, 172(3): 393-407.
8. Du Z, Sun T, Hacisuleyman E, et al. Integrative analyses reveal a long noncoding RNA-mediated sponge regulatory network in prostate cancer. Nat Commun, 2016, 7: 10982.
9. Batista PJ, Chang HY. Long noncoding RNAs: Cellular address codes in development and disease. Cell, 2013, 152(6): 1298-1307.
10. Seo D, Kim D, Chae Y, et al. The ceRNA network of lncRNA and miRNA in lung cancer. Genomics Inform, 2020, 18(4): e36.
11. Shen Y, Peng X, Shen C. Identification and validation of immune-related lncRNA prognostic signature for breast cancer. Genomics, 2020, 112(3): 2640-2646.
12. Xu C, Liu M, Jia D, et al. lncRNA TINCR SNPs and expression levels are associated with bladder cancer susceptibility. Genet Test Mol Biomarkers, 2021, 25(1): 31-41.
13. Salmena L, Poliseno L, Tay Y, et al. A ceRNA hypothesis: The Rosetta Stone of a hidden RNA language? Cell, 2011, 146(3): 353-358.
14. Su K, Wang N, Shao Q, et al. The role of a ceRNA regulatory network based on lncRNA MALAT1 site in cancer progression. Biomed Pharmacother, 2021, 137: 111389.
15. Liang Y, Rong X, Luo Y, et al. A novel long non-coding RNA LINC00355 promotes proliferation of lung adenocarcinoma cells by down-regulating miR-195 and up-regulating the expression of CCNE1. Cell Signal, 2020, 66: 109462.
16. Ma T, Hu Y, Guo Y, et al. Tumor-promoting activity of long noncoding RNA LINC00466 in lung adenocarcinoma via miR-144-regulated HOXA10 axis. Am J Pathol, 2019, 189(11): 2154-2170.
17. Han M, Gu Y, Lu P, et al. Exosome-mediated lncRNA AFAP1-AS1 promotes trastuzumab resistance through binding with AUF1 and activating ERBB2 translation. Mol Cancer, 2020, 19(1): 26.
18. Zhou Y, Shi X, Chen H, et al. Tumor immune microenvironment characterization of primary lung adenocarcinoma and lymph node metastases. Biomed Res Int, 2021, 2021: 5557649.
19. Dang Y, Ouyang X, Ren W, et al. LncRNA AFAP1-AS1 modulates the proliferation and invasion of gastric cancer cells by regulating AFAP1 via miR-205-5p. Cancer Manag Res, 2021, 13: 5163-5175.
20. Tang J, Zhong G, Wu J, et al. Long noncoding RNA AFAP1-AS1 facilitates tumor growth through enhancer of zeste homolog 2 in colorectal cancer. Am J Cancer Res, 2018, 8(5): 892-902.
21. Wu W, Bhagat TD, Yang X, 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(5): 956-966.
22. Sun J, Min H, Yu L, et al. The knockdown of LncRNA AFAP1-AS1 suppressed cell proliferation, migration, and invasion, and promoted apoptosis by regulating miR-545-3p/hepatoma-derived growth factor axis in lung cancer. Anticancer Drugs, 2021, 32(1): 11-21.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Foundation of ceRNA networks and functional validation of AFAP1-AS1 in lung adenocarcinoma

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