Long Non-coding RNA ZEB1-AS1 Promotes Tumorigenesis and Metastasis in Colorectal Cancer

Document Type: Research Article

Authors

Department of Biotechnology, Institute of Science and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran

Abstract

Emerging evidence implicates that a large fraction of human genome was transcribed but the transcripts known as long non coding RNA are not translated into proteins. They are contributing in different cellular processes, including cellular proliferation and apoptosis. LncRNAs were found to play critical roles in many diseases and act as key regulators in malignancies. In this study, we investigated the expression and clinical significance of ZEB1-AS1 in colorectal cancer. In the present study, 64 samples including 32 samples of colorectal tumor and 32 matched tumor marginal samples were obtained from Iran National Tumor Bank (Tehran, Iran). RNA extraction was performed with TRIzol reagent and cDNA was synthesized using MMULV reverse transcriptase enzyme. The expression of ZEB1-AS1 in tumors and marginal tissues was determined by using real time PCR. We found that the expression level of ZEB1-AS1 was much higher in tumor tissues compared to marginal samples. Moreover, in tumor group, ZEB1-AS1 expression was significantly upregulated in high-grade tumors in comparison to low-grade ones. Additionally, we observed the expression of  ZEB1-AS1 was much higher in lymph node metastatic tumors compared to non-lymph node metastatic ones. Our data showed that the ZEB1-AS1 was dramatically overexpressed in colorectal cancer tissues. The results of the study revealed that the expression of ZEB1-AS1 is correlated with tumor stage, lymph node metastasis and vascular invasion. Based on our findings, we suggested that ZEB1-AS1 might be considered as a tumor marker with potential diagnostic, prognostic and therapeutic value for aggressive and metastatic colorectal cancers.

Keywords


Anderson A, Caswell S, Macleod M, Craigie A, Stead M, Steele R, BeWel Team T. 2015. Awareness of lfestyle and colorectal cancer risk: Findings from the BeWEL study. Biomed Res Int 5: 1-5.

Azeem S, Gillani SW, Siddiqui A, Jandrajupalli SB, Poh V, Syed Sulaiman SA. 2015. Diet and colorectal cancer risk in Asia: a systematic review. Asian Pac J Cancer Prev 16: 5389-5396.

Brenner H, Kloor M, Pox CP. 2014. Colorectal cancer. Lancet 383: 1490-1502.

Deng J, Yang M, Jiang R, An N, Wang X, Liu B. 2017. Long non-coding RNA HOTAIR regulates the proliferation, self-renewal capacity, tumor formation and migration of the cancer stem-like cell (CSC) subpopulation enriched from breast cancer cells. Plos One 12:e0170860.

Fatica A, Bozzoni I. 2014. Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet 15: 7-21.

Fatima R, Akhade VS, Pal D, Rao SM. 2015. Long noncoding RNAs in development and cancer: potential biomarkers and therapeutic targets. Mol Cell Ther 3: 5-24.

Ghafouri Sabzevari F, Momeni-Moghaddam M, Farassati F, Rad A. 2016. Effect of EZH2 Inhibition on colorectal cancer cells: an in vitro study. J Genet Resour 2: 88-92.

Gontan C, Jonkers I, Gribnau J. 2011. Long noncoding RNAs and X chromosome inactivation. Prog Mol Subcell Biol 51: 43-64.

Jannat Alipoor F, Asadi MH, Torkzadeh-Mahani M. 2018a. MIAT lncRNA is overexpressed in breast cancer and its inhibition triggers senescence and G1 arrest in MCF7 cell line. J Cell Biochem 119: 6470-6481.

Jannat Alipoor F, Asadi MH, Torkzadeh-Mahani M. 2017b. LncRNA Miat promotes proliferation of cervical cancer cells and acts as an anti-apoptotic factor. J Genet Resour 3: 80-86.

Lemos AE, Ferreira LB, Batoreu NM, de Freitas PP, Bonamino MH, Gimba ER. 2016. PCA3 long noncoding RNA modulates the expression of key cancer-related genes in LNCaP prostate cancer cells. Tumour Biol 37: 11339-11348.

Li HJ, Sun XM, Li ZK, Yin QW, Pang H, Pan JJ, Li X, Chen W. 2017a. LncRNA UCA1 promotes mitochondrial function of bladder cancer via the MiR-195/ARL2 signaling pathway. Cell Physiol Biochem 43: 2548-2561.

Li L, Wang QF, Zou ML, He XA, Lv JJ. 2017b. Overexpressed lncRNA ZEB1-AS1 promotes cell invasion and angiogenesis through Wnt/beta-catenin signaling in non-small cell lung cancer. Int J Clin Exp Pathol 10: 3990-3997.

Li T, Xie J, Shen C, Cheng D, Shi Y, et al. 2016. Upregulation of long noncoding RNA ZEB1-AS1 promotes tumor metastasis and predicts poor prognosis in hepatocellular carcinoma. Oncogene 35: 1575-1584.

Liu C, Lin J. 2016. Long noncoding RNA ZEB1-AS1 acts as an oncogene in osteosarcoma by epigenetically activating ZEB1. Am J Transl Res 8: 4095-40105.

Liu C, Pan C, Cai Y, Wang H. 2017a. Interplay between long noncoding RNA ZEB1‐AS1 and miR‐200s regulates osteosarcoma cell proliferation and migration. J Cell Biochem 118: 2250-2260.

Liu Y-y, Chen ZH, Peng JJ, Wu JL, Yuan YJ, Zhai ET, Cai SR, He YL, Song W. 2017b. Up-regulation of long non-coding RNA XLOC_010235 regulates epithelial-to-mesenchymal transition to promote metastasis by associating with Snail1 in gastric cancer. Sci Rep 7: 2461-2470.

Liu Y, Sun Z, Zhu J, Xiao B, Dong J, Li X. 2017c. LncRNA-TCONS_00034812 in cell proliferation and apoptosis of pulmonary artery smooth muscle cells and its mechanism. J Cell Physiol 6: 4801-4814

Lv QL, Hu L, Chen SH, Sun B, Fu ML, et al. 2016. A long noncoding RNA ZEB1-AS1 promotes tumorigenesis and predicts poor prognosis in glioma. Int J Mol Sci 17(9). pii: E1431. doi: 10.3390/ijms17091431.

Nagano T, Fraser P. 2011. No-nonsense functions for long noncoding RNAs. Cell 145: 178-181.

Rezanejad bardaji H, Asadi MH, Yaghoobi MM. 2018. Long noncoding RNA VIM-AS1 promotes colorectal cancer progression and metastasis by inducing EMT. Eur J Cell Biol 97: 279-288.

Schmidt K, Joyce CE, Buquicchio F, Brown A, Ritz J, Distel RJ, Yoon CH, Novina CD. 2016. The lncRNA SLNCR1 Mediates melanoma invasion through a conserved SRA1-like region. Cell Rep 15: 2025-2037.

Wang YL, Bai Y, Yao WJ, Guo L, Wang ZM. 2015. Expression of long non-coding RNA ZEB1-AS1 in esophageal squamous cell carcinoma and its correlation with tumor progression and patient survival. Int J Clin Exp Pathol 8: 11871-11876.

Wapinski O, Chang HY. 2011. Long noncoding RNAs and human disease. Trends Cell Biol 21: 354-361.

Wu L, Zhang L, Zheng S. 2017. Role of the long non-coding RNA HOTAIR in hepatocellular carcinoma. Oncol Lett 14: 1233-1239.

Yang MH, Hu ZY, Xu C, Xie LY, Wang XY, Chen SY, Li G. 2015. MALAT1 promotes colorectal cancer cell proliferation/ migration/ invasion via PRKA kinase anchor protein 9. Biochim Biophys Acta 1852: 166-174.