Evaluation of Long Non-Coding RNAs: HNF1A-AS1 and MVIH Expressions and Their Clinical Significance in Human Gastric Cancer

Document Type : Research Article

Authors

1 Department of Genetics, Faculty of Basic Sciences, Shahrekord University, Shahrekord, Iran

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

3 Child Growth and Development Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

4 Biotechnology Research Institute, Shahrekord University, Shahrekord, Iran

Abstract

Gastric cancer is one of the most common cancers in the world. Late diagnosis is the main cause of the high rate of treatment failure and death among patients with gastric cancer; therefore identifying the molecular basis of cancer initiation and metastasis is so critical for developing efficient methods for early diagnosis and therapy. long non-coding RNAs (lncRNAs) are the largest group of noncoding RNAs, which are involved in cancer pathogenesis. Regarding the roles of lncRNA-HNF1A-AS1 and lncRNA-MVIH in cancer pathogenesis and progression, we aimed to evaluate expression profiles and clinicopathological relevance of these two genes in human gastric cancer. Real-time PCR was performed to assess relative gene expressions in 60 tumoral and non-tumoral gastric tissues. The association between gene expressions and clinicopathological characteristics were also analyzed. Expression and clinicopathological data of the lncRNA-HNF1A-AS1 from 318 gastric cancer patients were also downloaded from the TCGA database. HNF1A-AS1 was down-regulated in GC tissues and MVIH did not show any significant differential expression in GC tissues. Otherwise, the expression of lncRNA-HNF1A-AS1 was significantly higher in TCGA tumor samples. Furthermore, lncRNA-HNF1A-AS1 expression was associated with tumor metastasis and that of lncRNA-MVIH showed association with tumor grade and stage. lncRNA-HNF1A-AS1 expression status did not show any significant correlation with GC overall survival. In conclusion, lncRNA-HNF1A-S1 and lncRNA-MVIH genes may play a critical role in gastric cancer progression. Functional studies on the mechanism of action of these two lncRNAs could help to understand their role in gastric cancer progression.

Keywords


Anaya J. 2016. Oncolnc: linking TCGA survival data to mRNAs, miRNAs, and lncRNAs. Peer J Computer Science 4: e1780v1 doi: 10.7287/peerj.preprints.1780v1.
Baygi ME, Soheili ZS, Schmitz I, Sameie S, Schulz WA. 2010. Snail regulates cell survival and inhibits cellular senescence in human metastatic prostate cancer cell lines. Cell Biol Toxicol 26(6):553-567.
Brosnan CA, Voinnet O. 2009. The long and the short of noncoding RNAs. Curr Opin Cell Biol 21 (3): 416-425.
Chan AO. 2006. E-cadherin in gastric cancer. World journal of gastroenterology. World J Gastroenterol 12 (2): 199-203.
Chen T, Li E. 2006. Establishment and maintenance of DNA methylation patterns in mammals. Curr Top Microbiol Immunol 301: 179-201.
Correa P. Gastric cancer: overview. 2013. Gastroenterol Clin North Am 42 (2): 211-217.
Costa C, Giménez-Capitán A, Karachaliou N, Rosell R. 2013. Comprehensive molecular screening: from the RT-PCR to the RNA-seq. Transl Lung Cancer Res 2 (2): 87-91.
Danaei G, Vander Hoorn S, Lopez AD, Murray CJ, Ezzati M, group CRAc. 2005. Causes of cancer in the world: comparative risk assessment of nine behavioral and environmental risk factors. Lancet 366 (9499): 1784-1793.
Dang Y, Lan F, Ouyang X, Wang K, Lin Y, Yu Y, Wang L, Wang Y, Huang Q. 2015. Expression and clinical significance of long non-coding RNA HNF1A-AS1 in human gastric cancer. World J Surg Oncol 13: 302. doi: 10.1186/s12957-015-0706-3.
Emadi-Baygi M, Nikpour P, Emadi-Andani E. 2015. SIX1 overexpression in diffuse-type and grade III gastric tumors: Features that are associated with poor prognosis. Adv Biomed Res 4: 139. doi: 10.4103/2277-9175.161540.
Fang C, Qiu S, Sun F, Li W, Wang Z, Yue B, Wu X, Yan D. 2017. Long non-coding RNA HNF1A-AS1 mediated repression of miR-34a/SIRT1/p53 feedback loop promotes the metastatic progression of colon cancer by functioning as a competing endogenous RNA. Cancer lett 410: 50-62.
Fang Y, Fullwood MJ. 2016. Roles, functions, and mechanisms of long non-coding RNAs in cancer. Genom Proteom Bioinform 14 (1): 42-54.
Gibb EA, Vucic EA, Enfield KS, Stewart GL, Lonergan KM, Kennett JY, Becker-Santos DD, MacAulay CE, Lam S, Brown CJ. 2011. Human cancer long non-coding RNA transcriptomes. PloS One 6 (10): e25915.
Guo X, Zhang Y, Liu L, Yang W, Zhang Q. 2020. HNF1A-AS1 regulates cell migration, invasion and glycolysis via modulating miR-124/MYO6 in colorectal cancer cells. Onco Targets Ther 13: 1507-1518.
He Y, Meng X-M, Huang C, Wu B-M, Zhang L, Lv X-W, Li J. 2014. Long noncoding RNAs: Novel insights into hepatocelluar carcinoma. Cancer lett 344 (1): 20-27.
Lei B, Xu SP, Liang XS, Li YW, Zhang JF, Zhang GQ, Pang D. 2016. Long non-coding RNA MVIH is associated with poor prognosis and malignant biological behavior in breast cancer. Tumor Biol 37 (4): 5257-5264.
Li J, Han L, Roebuck P, Diao L, Liu L, Yuan Y, Weinstein JN, Liang H. 2015. TANRIC: an interactive open platform to explore the function of lncRNAs in cancer. Cancer res 75 (18): 3728-3737.
Liu H-T, Liu S, Liu L, Ma R-R, Gao P. 2018. EGR1-mediated transcription of lncRNA-HNF1A-AS1 promotes cell-cycle progression in gastric cancer. Cancer Res 78 (20): 5877-5890.
Liu L, Chen Y, Li Q, Duan P. 2019. lncRNA HNF1A‐AS1 modulates non–small cell lung cancer progression by targeting miR‐149‐5p/Cdk6. J Cell Biochem 120 (11): 18736-18750.
Liu Z, Li H, Fan S, Lin H, Lian W. 2019. STAT3-induced upregulation of long noncoding RNA HNF1A-AS1 promotes the progression of oral squamous cell carcinoma via activating Notch signaling pathway. Cancer Biol Ther 20 (4): 444-453.
Liu Z, Wei X, Zhang A, Li C, Bai J, Dong J. 2016. Long non-coding RNA HNF1A-AS1 functioned as an oncogene and autophagy promoter in hepatocellular carcinoma through sponging hsa-miR-30b-5p. Biochem Biophys Res Commun 473 (4): 1268-1275.
Malekzadeh R, Derakhshan MH, Malekzadeh Z. 2009. Gastric cancer in Iran: epidemiology and risk factors. Arch Iran Med 12 (6): 576-583.
Mathieu E-L, Belhocine M, Dao L, Puthier D, Spicuglia S. 2014. Functions of lncRNA in development and diseases. Med Sci (Paris) 30 (8-9): 790-796.
Müller S, Raulefs S, Bruns P, Afonso-Grunz F, Plötner A, Thermann R, Jäger C, Schlitter AM, Kong B, Regel I. 2015. Next-generation sequencing reveals novel differentially regulated mRNAs, lncRNAs, miRNAs, sdRNAs and a piRNA in pancreatic cancer. Mol Cancer 14: 94. doi: 10.1186/s12943-015-0358-5.
Nie F-q, Zhu Q, Xu T-p, Zou Y-f, Xie M, Sun M, Xia R, Lu K-h. 2014. Long non-coding RNA MVIH indicates a poor prognosis for non-small cell lung cancer and promotes cell proliferation and invasion. Tumor Biol 35 (8): 7587-7594.
Nikpour P, Emadi-Baygi M, Emadi-Andani E, Rahmati S. 2014. EYA1 Expression in gastric carcinoma and its association with clinicopathological characteristics: a pilot study. Med Oncol 31 (5): 955. doi: 10.1007/s12032-014-0955-y.
Nourbakhsh N, Emadi-Baygi M, Salehi R, Nikpour P. 2018. Gene expression analysis of two epithelial-mesenchymal transition-related genes: Long noncoding RNA-ATB and SETD8 in gastric cancer tissues. Adv Biomed Res 7: 42. doi: 10.4103/abr.abr-252-16.
Radmard AR. 2010. Five common cancers in Iran. Arch Iran Med 13 (2): 143-146.
Shi Y, Song Q, Yu S, Hu D, Zhuang X. 2015. Microvascular invasion in hepatocellular carcinoma overexpression promotes cell proliferation and inhibits cell apoptosis of hepatocellular carcinoma via inhibiting miR-199a expression. Onco Targets Ther 8: 2303-2310.
Wang C, Mou L, Chai H-X, Wang F, Yin Y-Z, Zhang X-Y. 2017. Long non-coding RNA HNF1A-AS1 promotes hepatocellular carcinoma cell proliferation by repressing NKD1 and P21 expression. Biomed Pharmacother 89: 926-932.
Wang G, Zhao W, Gao X, Zhang D, Li Y, Zhang Y, Li W. 2017. HNF1A-AS1 promotes growth and metastasis of esophageal squamous cell carcinoma by sponging miR‑214 to upregulate the expression of SOX-4. Int J Oncol 51 (2): 657-667.
Wang KC, Chang HY. 2011. Molecular mechanisms of long noncoding RNAs. Mol Cell 43 (6): 904-914.
Weinstein JN, Collisson EA, Mills GB, Shaw KRM, Ozenberger BA, Ellrott K, Shmulevich I, Sander C, Stuart JM, 2013. The cancer genome atlas pan-cancer analysis project. Nat Genet 45 (10): 1113-1120.
Wu Y, Liu H, Shi X, Yao Y, Yang W, Song Y. 2015. The long non-coding RNA HNF1A-AS1 regulates proliferation and metastasis in lung adenocarcinoma. Oncotarget 6 (11): 9160-9172.
Yang X, Song JH, Cheng Y, Wu W, Bhagat T, Yu Y, Abraham JM, Ibrahim S, Ravich W, Roland BC. 2014. Long non-coding RNA HNF1A-AS1 regulates proliferation and migration in oesophageal adenocarcinoma cells. Gut 63 (6): 881-890
Yuan SX, Yang F, Yang Y, Tao QF, Zhang J, Huang G, Yang Y, Wang RY, Yang S, Huo XS. 2012. Long noncoding RNA associated with microvascular invasion in hepatocellular carcinoma promotes angiogenesis and serves as a predictor for hepatocellular carcinoma patients' poor recurrence‐free survival after hepatectomy. Hepatology 56 (6): 2231-2241.
Zhan Y, Li Y, Guan B, Wang Z, Peng D, Chen Z, He A, He S, Gong Y, Li X. 2017. Long non-coding RNA HNF1A-AS1 promotes proliferation and suppresses apoptosis of bladder cancer cells through upregulating Bcl-2. Oncotarget 8 (44): 76656-76665.
Zhang G, An X, Zhao H, Zhang Q, Zhao H. 2018. Long non-coding RNA HNF1A-AS1 promotes cell proliferation and invasion via regulating miR-17-5p in non-small cell lung cancer. Biomed Pharmacother 98: 594-599.