MicroRNA‑373 is upregulated and targets TNFAIP1 in human gastric cancer, contributing to tumorigenesis

Zhang,Xiaoting; Li,Xiaofeng; Tan,Zhiwen; Liu,Xizhi; Yang,Celi; Ding,Xiaofeng; Hu,Xiang; Zhou,Jianlin; Xiang,Shuanglin; Zhou,Chang; Zhang,Jian

doi:10.3892/ol.2013.1534

MicroRNA‑373 is upregulated and targets TNFAIP1 in human gastric cancer, contributing to tumorigenesis

Authors:
- Xiaoting Zhang
- Xiaofeng Li
- Zhiwen Tan
- Xizhi Liu
- Celi Yang
- Xiaofeng Ding
- Xiang Hu
- Jianlin Zhou
- Shuanglin Xiang
- Chang Zhou
- Jian Zhang
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Affiliations: Key Laboratory of Protein Chemistry and Developmental Biology of State Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, Hunan 410081, P.R. China
Published online on: August 19, 2013 https://doi.org/10.3892/ol.2013.1534
Pages: 1427-1434

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Abstract

The role of microRNAs (miRNAs) in regulating gene expression is currently an area of intense interest. Previous studies have shown that miRNA‑372 plays crucial roles in gastric tumorigenesis by targeting the mRNA of tumor necrosis factor, α‑induced protein 1 (TNFAIP1). The present study showed that miR‑373 is upregulated in gastric adenocarcinoma tissue and gastric carcinoma cell lines when compared to normal gastric tissues. The overexpression of miR‑373 in the gastric cancer cells increased cell proliferation. A bioinformatics search revealed a conserved target site within the 3' untranslated region (UTR) of TNFAIP1, an immediate‑early response gene of the endothelium induced by TNF‑α. The overexpression of miR‑373 caused the suppression of a luciferase reporter containing the TNFAIP1 3'UTR in the HEK293 cells and reduced the levels of TNFAIP1 protein in the AGS cells. The mRNA levels of TNFAIP1 in the gastric cancer and normal gastric tissues were negatively correlated with the expression levels of miR‑373 in these tissues. Moreover, the knockdown of TNFAIP1 had a similar effect to the overexpression of miR‑373. The overexpression of TNFAIP1 may partly rescue the inhibition of proliferation caused by the inhibitor, miR‑373‑ASO. Taken together, these findings demonstrate an oncogenic role for miR‑373, similar to that of miR‑372, in controlling cell growth through the downregulation of TNFAIP1.

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1	Kamangar F, Dores GM and Anderson WF: Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 24:2137–2150. 2006. View Article : Google Scholar
2	Catalano V, Labianca R, Beretta GD, Gatta G, de Braud F and Van Cutsem E: Gastric cancer. Crit Rev Oncol Hematol. 71:127–164. 2009. View Article : Google Scholar
3	Gao C, Zhang Z, Liu W, Xiao S, Gu W and Lu H: Reduced microRNA-218 expression is associated with high nuclear factor kappa B activation in gastric cancer. Cancer. 116:41–49. 2010.PubMed/NCBI
4	Shah MA, Jhawer M, Ilson DH, et al: Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma. J Clin Oncol. 29:868–874. 2011. View Article : Google Scholar : PubMed/NCBI
5	Mukherji S, Ebert MS, Zheng GX, Tsang JS, Sharp PA and van Oudenaarden A: MicroRNAs can generate thresholds in target gene expression. Nat Genet. 43:854–859. 2011. View Article : Google Scholar : PubMed/NCBI
6	Pichinuk E, Broday L and Wreschner DH: Endogenous RNA cleavages at the ribosomal SRL site likely reflect miRNA (miR) mediated translational suppression. Biochem Biophys Res Commun. 414:706–711. 2011. View Article : Google Scholar : PubMed/NCBI
7	Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 6:857–866. 2006. View Article : Google Scholar : PubMed/NCBI
8	Zhang B, Pan X, Cobb GP and Anderson TA: microRNAs as oncogenes and tumor suppressors. Dev Biol. 302:1–12. 2007. View Article : Google Scholar : PubMed/NCBI
9	Xiao B, Guo J, Miao Y, et al: Detection of miR-106a in gastric carcinoma and its clinical significance. Clin Chim Acta. 400:97–102. 2009. View Article : Google Scholar : PubMed/NCBI
10	Zhang Z, Li Z, Gao C, et al: miR-21 plays a pivotal role in gastric cancer pathogenesis and progression. Lab Invest. 88:1358–1366. 2008. View Article : Google Scholar : PubMed/NCBI
11	Voorhoeve PM, le Sage C, Schrier M, et al: A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell. 124:1169–1181. 2006. View Article : Google Scholar
12	Lee KH, Goan YG, Hsiao M, et al: MicroRNA-373 (miR-373) post-transcriptionally regulates large tumor suppressor, homolog 2 (LATS2) and stimulates proliferation in human esophageal cancer. Exp Cell Res. 315:2529–2538. 2009. View Article : Google Scholar
13	Zhou C, Li X, Zhang X, et al: microRNA-372 maintains oncogene characteristics by targeting TNFAIP1 and affects NFκB signaling in human gastric carcinoma cells. Int J Oncol. 42:635–642. 2013.PubMed/NCBI
14	Hamilton SR and Aaltonen LA: Pathology and genetics Tumours of the digestive system. WHO Classification of Tumours. Kleihues P and Sobin LH: 2. IARC Press; Lyon: 2000
15	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.
16	Zeng Y and Cullen BR: Sequence requirements for micro RNA processing and function in human cells. RNA. 9:112–123. 2003. View Article : Google Scholar : PubMed/NCBI
17	Cho WJ, Shin JM, Kim JS, et al: miR-372 regulates cell cycle and apoptosis of ags human gastric cancer cell line through direct regulation of LATS2. Mol Cells. 28:521–527. 2009. View Article : Google Scholar : PubMed/NCBI
18	Chan SH, Wu CW, Li AF, Chi CW and Lin WC: miR-21 microRNA expression in human gastric carcinomas and its clinical association. Anticancer Res. 28:907–911. 2008.PubMed/NCBI
19	Lai KW, Koh KX, Loh M, et al: MicroRNA-130b regulates the tumour suppressor RUNX3 in gastric cancer. Eur J Cancer. 46:1456–1463. 2010. View Article : Google Scholar : PubMed/NCBI
20	Motoyama K, Inoue H, Nakamura Y, Uetake H, Sugihara K and Mori M: Clinical significance of high mobility group A2 in human gastric cancer and its relationship to let-7 microRNA family. Clin Cancer Res. 14:2334–2340. 2008. View Article : Google Scholar : PubMed/NCBI
21	Ueda T, Volinia S, Okumura H, et al: Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis. Lancet Oncol. 11:136–146. 2010. View Article : Google Scholar : PubMed/NCBI
22	Zhang Y, Chao T, Li R, et al: MicroRNA-128 inhibits glioma cells proliferation by targeting transcription factor E2F3a. J Mol Med (Berl). 87:43–51. 2009. View Article : Google Scholar : PubMed/NCBI
23	Spizzo R, Nicoloso M, Lupini L, et al: miR-145 participates with TP53 in a death-promoting regulatory loop and targets estrogen receptor-alpha in human breast cancer cells. Cell Death Differ. 17:246–254. 2010. View Article : Google Scholar
24	Hayashita Y, Osada H, Tatematsu Y, et al: A polycistronic microRNA cluster, miR-17–92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res. 65:9628–9632. 2005.
25	Martinez NJ and Gregory RI: MicroRNA gene regulatory pathways in the establishment and maintenance of ESC identity. Cell Stem Cell. 7:31–35. 2010. View Article : Google Scholar : PubMed/NCBI
26	Zhou J, Hu X, Xiong X, et al: Cloning of two rat PDIP1 related genes and their interactions with proliferating cell nuclear antigen. J Exp Zool A Comp Exp Biol. 303:227–240. 2005. View Article : Google Scholar : PubMed/NCBI
27	Link CD, Taft A, Kapulkin V, et al: Gene expression analysis in a transgenic Caenorhabditis elegans Alzheimer’s disease model. Neurobiol Aging. 24:397–413. 2003. View Article : Google Scholar : PubMed/NCBI
28	Yang L, Zhou A, Li H, et al: Expression profile in the cell lines of human TNFAIP1 gene. Yi Chuan. 28:918–922. 2006.(In Chinese).
29	Wolf F, Marks R, Sarma V, et al: Characterization of a novel tumor necrosis factor-alpha-induced endothelial primary response gene. J Biol Chem. 267:1317–1326. 1992.PubMed/NCBI
30	Yang L, Liu N, Hu X, et al: CK2 phosphorylates TNFAIP1 to affect its subcellular localization and interaction with PCNA. Mol Biol Rep. 37:2967–2973. 2010. View Article : Google Scholar : PubMed/NCBI