MicroRNA-203 inhibits the malignant progression of neuroblastoma by targeting Sam68

Zhao,Dongju; Tian,Yunjiao; Li,Peiling; Wang,Limin; Xiao,Aiju; Zhang,Mingqiu; Shi,Taixin

doi:10.3892/mmr.2015.4013

MicroRNA-203 inhibits the malignant progression of neuroblastoma by targeting Sam68

Authors:
- Dongju Zhao
- Yunjiao Tian
- Peiling Li
- Limin Wang
- Aiju Xiao
- Mingqiu Zhang
- Taixin Shi
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Affiliations: Department of Pediatrics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China, Department of Interventional Radiography, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China
Published online on: July 1, 2015 https://doi.org/10.3892/mmr.2015.4013
Pages: 5554-5560

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Abstract

Neuroblastoma (NB) is the most common solid extracranial tumor in children. However, the molecular mechanism of NB remains to be elucidated. In the present study, reverse transcription quantitative polymerase chain reaction data demonstrated that the expression of Sam68 was significantly upregulated in NB tissues compared with their matched adjacent normal tissues. Furthermore, it was revealed that reduced expression of miR‑203 and increased expression of Sam68 co‑existed in NB tissues. Knockdown of Sam68 reduced the proliferation, migration and invasion of human SK‑N‑SH and SH‑SY5Y NB cells. Similarly, overexpression of miR‑203 also inhibited the proliferation, migration and invasion of these two cell lines. It was further demonstrated that the protein expression level of Sam68 was negatively mediated by miR‑203 in the SK‑N‑SH and SH‑SY5Y NB cells. Additionally, data from a dual luciferase reporter assay confirmed that miR‑203 directly targeted Sam68 by binding to its 3'‑untranslated region. In conclusion, the present study suggested for the first time, to the best of our knowledge, that the aberrant downregulation of miR‑203 may contribute to the aberrant upregulation of Sam68 in NB and that miR‑203 has an inhibitory role in malignant progression of NB by targeting Sam68. The present study provided evidence to support miR-203/Sam68 as a novel diagnostic or therapeutic targets for NB.

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1	Fulda S: The PI3K/Akt/mTOR pathway as therapeutic target in neuroblastoma. Curr Cancer Drug Targets. 9:729–737. 2009. View Article : Google Scholar : PubMed/NCBI
2	Jrebi NY, Iqbal CW, Joliat GR, Sebo TJ and Farley DR: Review of our experience with neuroblastoma and ganglioneuroblastoma in adults. World J Surg. 2871–2874. 2014. View Article : Google Scholar : PubMed/NCBI
3	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
4	Baer C, Claus R and Plass C: Genome-wide epigenetic regulation of miRNAs in cancer. Cancer Res. 73:473–477. 2013. View Article : Google Scholar : PubMed/NCBI
5	Vogel G and Richard S: Emerging roles for Sam68 in adipogenesis and neuronal development. RNA Biol. 9:1129–1133. 2012. View Article : Google Scholar : PubMed/NCBI
6	Najib S, Martin-Romero C, Gonzalez-Yanes C and Sanchez-Margalet V: Role of Sam68 as an adaptor protein in signal transduction. Cell Mol Life Sci. 62:36–43. 2005. View Article : Google Scholar
7	Lukong KE and Richard S: Sam68, the KH domain-containing superSTAR. Biochim Biophys Acta. 1653:73–86. 2003.PubMed/NCBI
8	Chen SW, Zhang Q, Yang AK, Li Z, Zhong Y, Li H, Zeng Y, Zhuang SM, Wang LP, Song LB, et al: Overexpression and cytoplasmic localization of Sam68 correlate with tumour progression and poor prognosis in patients with clinically N0 oral tongue cancer. Head Neck Oncol. 4:612012.
9	Zhang Z, Xu Y, Sun N, Zhang M, Xie J and Jiang Z: High Sam68 expression predicts poor prognosis in non-small cell lung cancer. Clin Transl Oncol. 16:886–891. 2014. View Article : Google Scholar : PubMed/NCBI
10	Arocho A, Chen B, Ladanyi M and Pan Q: Validation of the 2-DeltaDeltaCt calculation as an alternate method of data analysis for quantitative PCR of BCR-ABL P210 transcripts. Diagn mol pathol. 15:56–61. 2006. View Article : Google Scholar : PubMed/NCBI
11	Sánchez-Jiménez F and Sánchez-Margalet V: Role of Sam68 in post-transcriptional gene regulation. Int J Mol Sci. 14:23402–23419. 2013. View Article : Google Scholar : PubMed/NCBI
12	Fu K, Sun X, Zheng W, Wier EM, Hodgson A, Tran DQ, Richard S and Wan F: Sam68 modulates the promoter specificity of NF-kB and mediates expression of CD25 in activated T cells. Nat Commun. 4:19092013. View Article : Google Scholar
13	Liao WT, Liu JL, Wang ZG, Cui YM, Shi L, Li TT, Zhao XH, Chen XT, Ding YQ and Song LB: High expression level and nuclear localization of Sam68 are associated with progression and poor prognosis in colorectal cancer. BMC Gastroenterol. 14:1262014.
14	Li Z, Yu CP, Zhong Y, Liu TJ, Huang QD, Zhao XH, Huang H, Tu H, Jiang S, Zhang Y, et al: Sam68 expression and cytoplasmic localization is correlated with lymph node metastasis as well as prognosis in patients with early-stage cervical cancer. Ann Oncol. 23:638–646. 2012. View Article : Google Scholar
15	Zhao X, Li Z, He B, Liu J, Li S, Zhou L, Pan C, Yu Z and Xu Z: Sam68 is a novel marker for aggressive neuroblastoma. Onco Targets Ther. 6:1751–1760. 2013.PubMed/NCBI
16	Furuta M, Kozaki KI, Tanaka S, Arii S, Imoto I and Inazawa J: miR-124 and miR-203 are epigenetically silenced tumor-suppressive microRNAs in hepatocellular carcinoma. Carcinogenesis. 31:766–776. 2010. View Article : Google Scholar
17	Greither T, Grochola LF, Udelnow A, Lautenschlager C, Wurl P and Taubert H: Elevated expression of microRNAs 155, 203, 210 and 222 in pancreatic tumors is associated with poorer survival. Int J Cancer. 126:73–80. 2010. View Article : Google Scholar
18	He J, Deng Y, Yang G and Xie W: MicroRNA-203 down-regulation is associated with unfavorable prognosis in human glioma. J Surg Oncol. 108:121–125. 2013. View Article : Google Scholar : PubMed/NCBI
19	Cheung TH, Man KN, Yu MY, Yim SF, Siu NS, Lo KW, Doran G, Wong RR, Wang VW, Smith DI, et al: Dysregulated microRNAs in the pathogenesis and progression of cervical neoplasm. Cell Cycle. 11:2876–2884. 2012. View Article : Google Scholar : PubMed/NCBI
20	Boll K, Reiche K, Kasack K, Mörbt N, Kretzschmar AK, Tomm JM, Verhaegh G, Schalken J, von Bergen M, Horn F, et al: MiR-130a, miR-203 and miR-205 jointly repress key oncogenic pathways and are downregulated in prostate carcinoma. Oncogene. 32:277–285. 2013. View Article : Google Scholar
21	Kozubek J, Ma Z, Fleming E, Duggan T, Wu R, Shin DG and Dadras SS: In-depth characterization of microRNA transcriptome in melanoma. PLoS One. 8:e726992013. View Article : Google Scholar : PubMed/NCBI
22	Schetter AJ, Leung SY, Sohn JJ, Zanetti KA, Bowman ED, Yanaihara N, Yuen ST, Chan TL, Kwong DL, Au GK, et al: MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA. 299:425–436. 2008. View Article : Google Scholar : PubMed/NCBI
23	Wang C, Wang X, Liang H, Wang T, Yan X, Cao M, Wang N, Zhang S, Zen K, Zhang C, et al: miR-203 Inhibits cell proliferation and migration of lung cancer cells by targeting PKCα. PLoS One. 8:e739852013. View Article : Google Scholar
24	Wang C, Zheng X, Shen C and Shi Y: MicroRNA-203 suppresses cell proliferation and migration by targeting BIRC5 and LASP1 in human triple-negative breast cancer cells. J Exp Clin Cancer Res. 31:582012. View Article : Google Scholar : PubMed/NCBI
25	Yuan Y, Zeng ZY, Liu XH, Gong DJ, Tao J, Cheng HZ and Huang SD: MicroRNA-203 inhibits cell proliferation by repressing ΔNp63 expression in human esophageal squamous cell carcinoma. BMC Cancer. 11:572011. View Article : Google Scholar
26	Tian L, Li M, Ge J, Guo Y, Sun Y, Liu M and Xiao H: MiR-203 is downregulated in laryngeal squamous cell carcinoma and can suppress proliferation and induce apoptosis of tumours. Tumour Biol. 35:5953–5963. 2014. View Article : Google Scholar : PubMed/NCBI
27	Bian K, Fan J, Zhang X, Yang XW, Zhu HY, Wang L, Sun JY, Meng YL, Cui PC, Cheng SY, et al: MicroRNA-203 leads to G1 phase cell cycle arrest in laryngeal carcinoma cells by directly targeting survivin. FEBS Lett. 586:804–809. 2012. View Article : Google Scholar : PubMed/NCBI
28	Abella V, Valladares M, Rodriguez T, Haz M, Blanco M, Tarrío N, Iglesias P, Aparicio LA and Figueroa A: miR-203 regulates cell proliferation through its influence on Hakai expression. PLoS One. 7:e525682012. View Article : Google Scholar
29	Dontula R, Dinasarapu A, Chetty C, Pannuru P, Herbert E, Ozer H and Lakka SS: MicroRNA 203 modulates glioma cell migration via Robo1/ERK/MMP-9 Signaling. Genes Cancer. 4:285–296. 2013. View Article : Google Scholar : PubMed/NCBI
30	Noguchi S, Kumazaki M, Yasui Y, Mori T, Yamada N and Akao Y: MicroRNA-203 regulates melanosome transport and tyrosinase expression in melanoma cells by targeting kinesin superfamily protein 5b. J Invest Dermatol. 134:461–469. 2014. View Article : Google Scholar
31	Noguchi S, Mori T, Otsuka Y, Yamada N, Yasui Y, Iwasaki J, Kumazaki M, Maruo K and Akao Y: Anti-oncogenic microRNA-203 induces senescence by targeting E2F3 protein in human melanoma cells. J Biol Chem. 287:11769–11777. 2012. View Article : Google Scholar : PubMed/NCBI
32	Takeshita N, Mori M, Kano M, Hoshino I, Akutsu Y, Hanari N, Yoneyama Y, Ikeda N, Isozaki Y, Maruyama T, et al: miR-203 inhibits the migration and invasion of esophageal squamous cell carcinoma by regulating LASP1. Int J Oncol. 41:1653–1661. 2012.PubMed/NCBI
33	Yu X, Jiang X, Li H, Guo L, Jiang W and Lu SH: MiR-203 inhibits the proliferation and self-renewal of esophageal cancer stem-like cells by suppressing stem renewal factor Bmi-1. Stem Cells Dev. 23:576–585. 2014. View Article : Google Scholar