Augmented expression levels of lncRNAs ecCEBPA and UCA1 in gastric cancer tissues and their clinical significance

Document Type : Original Article


1 Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Genetics, School of Basic Sciences, Shahrekord University, Shahrekord, Iran

3 Research Institute of Biotechnology, School of Basic Sciences, Shahrekord University, Shahrekord, Iran

4 Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran


Objective(s): As the second cause of cancer death, gastric cancer (GC) is one of the eminent dilemmas all over the world, therefore investigating the molecular mechanisms involved in this cancer is pivotal. Unrestricted proliferation is one of the characteristics of cancerous cells, which is due to deficiency in cell regulatory systems. Long non-coding RNAs (lncRNAs) have emerged as critical regulators of the epigenome. lncRNA extra coding CEBPA (ecCEBPA) is involved in DNA methylation. This lncRNA reduces CEBPA promoter methylation by interacting with DNA methyltransferase 1. lncRNA UCA1 (urothelial carcinoma-associated 1) elevates cell proliferation through the PI3K/Akt signaling pathway which has a critical role in cell growth and apoptosis. The aim of this study was to examine the expression of ecCEBPA and UCA1 genes in GC tissues as well as their clinical significance.
Materials and Methods: Total RNA extraction, cDNA synthesis, and quantitative real-time PCR were performed for cells and 80 paired GC tissues. Furthermore, clinical relevance of UCA1 expression was investigated in TCGA cohort data.
Results: Our results showed ecCEBPA and UCA1 over-expression in GC tissues. Furthermore, lncRNAs associations with clinicopathological features were demonstrated both in the current and TCGA cohort. Kaplan-Meier analysis indicated that patients with higher UCA1 expression had a worse overall survival in the case of pancreatic and lung adenocarcinomas but not other solid cancer types including GC.
Conclusion: These data demonstrate UCA1 and ecCEBPA involvement in GC and suggest that these lncRNAs might be useful as diagnostic/ prognostic biomarkers in cancer.


1. Nagini S. Carcinoma of the stomach: A review of epidemiology, pathogenesis, molecular genetics and chemoprevention. World J Gastrointest Oncol 2012; 4:156-169.
2.Gutschner T, Diederichs S. The hallmarks of cancer: a long non-coding RNA point of view. RNA biology 2012; 9:703-719.
3.Wang XS, Zhang Z, Wang HC, Cai JL, Xu QW, Li MQ, et al. Rapid identification of UCA1 as a very sensitive and specific unique marker for human bladder carcinoma. Clin Cancer Res 2006; 12:4851-4858.
4.Cheng N, Cai W, Ren S, Li X, Wang Q, Pan H, et al. Long non-coding RNA UCA1 induces non-T790M acquired resistance to EGFR-TKIs by activating the AKT/mTOR pathway in EGFR-mutant non-small cell lung cancer. Oncotarget 2015; 6:23582-23593.
5.Fang Z, Wu L, Wang L, Yang Y, Meng Y, Yang H. Increased expression of the long non-coding RNA UCA1 in tongue squamous cell carcinomas: a possible correlation with cancer metastasis. Oral Surg Oral Med Oral Pathol Oral Radiol 2014; 117:89-95.
6.Li JY, Ma X, Zhang CB. Overexpression of long non-coding RNA UCA1 predicts a poor prognosis in patients with esophageal squamous cell carcinoma. Int J Clin Exp Pathol 2014; 7:7938-7944.
7.Liu SP, Yang JX, Cao DY, Shen K. Identification of differentially expressed long non-coding RNAs in human ovarian cancer cells with different metastatic potentials. Cancer Biol Med 2013; 10:138-141.
8.Tian Y, Zhang X, Hao Y, Fang Z, He Y. Potential roles of abnormally expressed long noncoding RNA UCA1 and Malat-1 in metastasis of melanoma. Melanoma Res 2014; 24:335-341.
9. Wang F, Ying HQ, He BS, Pan YQ, Deng QW, Sun HL, et al. Upregulated lncRNA-UCA1 contributes to progression of hepatocellular carcinoma through inhibition of miR-216b and activation of FGFR1/ERK signaling pathway. Oncotarget 2015; 6:7899-7917.
10. Huang J, Zhou N, Watabe K, Lu Z, Wu F, Xu M, et al. Long non-coding RNA UCA1 promotes breast tumor growth by suppression of p27 (Kip1). Cell Death Dis 2014; 5:e1008.
11.Yang C, Li X, Wang Y, Zhao L, Chen W. Long non-coding RNA UCA1 regulated cell cycle distribution via CREB through PI3-K dependent pathway in bladder carcinoma cells. Gene 2012; 496:8-16.
12. Han Y, Yang YN, Yuan HH, Zhang TT, Sui H, Wei XL, et al. UCA1, a long non-coding RNA up-regulated in colorectal cancer influences cell proliferation, apoptosis and cell cycle distribution. Pathology 2014; 46:396-401.
13. Xue M, Li X, Wu W, Zhang S, Wu S, Li Z, et al. Upregulation of long non-coding RNA urothelial carcinoma associated 1 by CCAAT/enhancer binding protein alpha contributes to bladder cancer cell growth and reduced apoptosis. Oncol Rep 2014; 31:1993-2000.
14.Wang ZQ, Cai Q, Hu L, He CY, Li JF, Quan ZW, et al. Long noncoding RNA UCA1 induced by SP1 promotes cell proliferation via recruiting EZH2 and activating AKT pathway in gastric cancer. Cell Death Dis 2017; 8:e2839.
15. He Z, Wang Y, Huang G, Wang Q, Zhao D, Chen L. The lncRNA UCA1 interacts with miR-182 to modulate glioma proliferation and migration by targeting iASPP. Arch Biochem Biophys 2017; 623-624:1-8.
16. Fang Q, Chen X, Zhi X. Long non-Coding RNA (LncRNA) urothelial carcinoma associated 1 c(UCA1) increases multi-drug resistance of gastric cancer via downregulating miR-27b. Med Sci Monit 2016; 22:3506-3513.
17. Di Ruscio A, Ebralidze AK, Benoukraf T, Amabile G, Goff LA, Terragni J, et al. DNMT1-interacting RNAs block gene-specific DNA methylation. Nature 2013; 503:371-376.
18. Emadi-Baygi M, Nikpour P, Mohammad-Hashem F, Maracy MR, Haghjooy-Javanmard S. MSI2 expression is decreased in grade II of gastric carcinoma. Pathol Res Pract  2013; 209:689-91.
19. Rezaei M, Emadi-Baygi M, Hoffmann MJ, Schulz WA, Nikpour P. Altered expression of LINC-ROR in cancer cell lines and tissues. Tumour Biol 2016; 37:1763-1769.
20. Nikpour P, Emadi-Baygi M, Emadi-Andani E, Rahmati S. EYA1 expression in gastric carcinoma and its association with clinicopathological characteristics: a pilot study. Med Oncol 2014; 31:955.
21. Li J, Han L, Roebuck P, Diao L, Liu L, Yuan Y, et al. TANRIC: an interactive open platform to explore the function of lncRNAs in cancer. Cancer Res 2015; 75:3728-3737.
22. Cancer Genome Atlas Research N, Weinstein JN, Collisson EA, Mills GB, Shaw KR, Ozenberger BA, et al. The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet 2013; 45:1113-1120.
23. Anaya J. OncoLnc: Linking TCGA survival data to mRNAs, miRNAs, and lncRNAs. PeerJ Prepr 2016; 4:e1780v1781.
24. Emadi Baygi M, Soheili ZS, Schmitz I, Sameie S, Schulz WA. Snail regulates cell survival and inhibits cellular senescence in human metastatic prostate cancer cell lines. Cell Biol Toxicol 2010; 26:553-567.
25. Zuo ZK, Gong Y, Chen XH, Ye F, Yin ZM, Gong QN, et al. TGFbeta1-induced lncRNA UCA1 upregulation promotes gastric cancer invasion and migration. DNA Cell Biol 2017; 36:159-167.
26. Gao J, Cao R, Mu H. Long non-coding RNA UCA1 may be a novel diagnostic and predictive biomarker in plasma for early gastric cancer. Int J Clin Exp Pathol 2015; 8:12936-12942.
27. Zheng Q, Wu F, Dai WY, Zheng DC, Zheng C, Ye H, et al. Aberrant expression of UCA1 in gastric cancer and its clinical significance. Clin Transl Oncol 2015; 17:640-646.