MicroRNA‑219 exerts a tumor suppressive role in glioma via targeting Sal‑like protein 4

Jiang,Botao; Li,Min; Ji,Fang; Nie,Yaxiong

doi:10.3892/etm.2017.5292

MicroRNA‑219 exerts a tumor suppressive role in glioma via targeting Sal‑like protein 4

Authors:
- Botao Jiang
- Min Li
- Fang Ji
- Yaxiong Nie
View Affiliations

Affiliations: Department of Neurology, First Hospital of Changsha, Changsha, Hunan 430100, P.R. China, Department of Nephrology, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China, Teaching and Research Office of Medical Imaging, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China, Department of Neurology, First Affiliated Hospital of Nanhua University, Hengyang, Hunan 421001, P.R. China
Published online on: October 12, 2017 https://doi.org/10.3892/etm.2017.5292
Pages: 6213-6221

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

MicroRNAs (miRs) serve important roles in the development and progression of various human cancer types, including glioma. Recently, miR‑219 has been suggested to function as a tumor suppressor in glioma; however, the underlying mechanism remains largely unknown. The aim of this study was to investigate the regulatory mechanism of miR‑219 in the malignant phenotypes of glioma cells. Quantitative polymerase chain reaction (qPCR) and western blotting were conducted to examine the mRNA and protein expression. An MTT assay, wound healing assay and Transwell assay were used to study cell proliferation, migration and invasion. The qPCR data indicated that the expression of miR‑219 was significantly decreased in glioma tissues compared with normal brain tissues. In addition, a low expression of miR‑219 was identified to be associated with an advanced pathological grade. In vitro experiments demonstrated that miR‑219 was also downregulated in several common glioma cell lines, including A172, U87, U251 and U373, when compared with that in normal astrocytes. Ectopic expression of miR‑219 caused a significant decrease in U87 cell proliferation, migration and invasion. Luciferase reporter assay data indicated that Sal‑like protein 4 (SALL4) was a direct target gene of miR‑219, while the protein expression of SALL4 was negatively regulated by miR‑219 in U87 cells. Furthermore, SALL4 was significantly upregulated in glioma tissues and cell lines, and upregulation of SALL4 was associated with a higher pathological grade. Furthermore, overexpression of SALL4 significantly attenuated the suppressive effects of miR‑219 on U87 cell proliferation, migration and invasion, suggesting that miR‑219 serves a suppressive role in glioma growth and metastasis via targeting SALL4. Therefore, the present study highlighted the clinical significance of the miR‑219/SALL4 axis in glioma.

View Figures

View References

1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI
3	Marumoto T and Saya H: Molecular biology of glioma. Adv Exp Med Biol. 746:2–11. 2012. View Article : Google Scholar : PubMed/NCBI
4	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
5	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
6	Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M and Croce CM: Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA. 101:pp. 2999–3004. 2004, View Article : Google Scholar : PubMed/NCBI
7	Croce CM and Calin GA: miRNAs, cancer, and stem cell division. Cell. 122:6–7. 2005. View Article : Google Scholar : PubMed/NCBI
8	An L, Liu Y, Wu A and Guan Y: microRNA-124 inhibits migration and invasion by down-regulating ROCK1 in glioma. PLoS One. 8:e694782013. View Article : Google Scholar : PubMed/NCBI
9	Jia Z, Wang K, Wang G, Zhang A and Pu P: MiR-30a-5p antisense oligonucleotide suppresses glioma cell growth by targeting SEPT7. PLoS One. 8:e550082013. View Article : Google Scholar : PubMed/NCBI
10	Lei H, Zou D, Li Z, Luo M, Dong L, Wang B, Yin H, Ma Y, Liu C, Wang F, et al: MicroRNA-219-2-3p functions as a tumor suppressor in gastric cancer and is regulated by DNA methylation. PLoS One. 8:e603692013. View Article : Google Scholar : PubMed/NCBI
11	Huang N, Lin J, Ruan J, Su N, Qing R, Liu F, He B, Lv C, Zheng D and Luo R: MiR-219-5p inhibits hepatocellular carcinoma cell proliferation by targeting glypican-3. FEBS Lett. 586:884–891. 2012. View Article : Google Scholar : PubMed/NCBI
12	Jiang Y, Yin L, Jing H and Zhang H: MicroRNA-219-5p exerts tumor suppressor function by targeting ROBO1 in glioblastoma. Tumour Biol. 36:8943–8951. 2015. View Article : Google Scholar : PubMed/NCBI
13	Rao SA, Arimappamagan A, Pandey P, Santosh V, Hegde AS, Chandramouli BA and Somasundaram K: miR-219-5p inhibits receptor tyrosine kinase pathway by targeting EGFR in glioblastoma. PLoS One. 8:e631642013. View Article : Google Scholar : PubMed/NCBI
14	Komori T: The 2016 WHO classification of tumours of the central nervous system: The major points of revision. Neurol Med Chir (Tokyo). 57:301–311. 2017. View Article : Google Scholar : PubMed/NCBI
15	Terret C, Albrand G, Moncenix G and Droz JP: Karnofsky performance scale (KPS) or physical performance test (PPT)? That is the question. Crit Rev Oncol Hematol. 77:142–147. 2011. View Article : Google Scholar : PubMed/NCBI
16	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. View Article : Google Scholar : PubMed/NCBI
17	Shi JA, Lu DL, Huang X and Tan W: miR-219 inhibits the proliferation, migration and invasion of medulloblastoma cells by targeting CD164. Int J Mol Med. 34:237–243. 2014. View Article : Google Scholar : PubMed/NCBI
18	Rao SA, Santosh V and Somasundaram K: Genome-wide expression profiling identifies deregulated miRNAs in malignant astrocytoma. Mod Pathol. 23:1404–1417. 2010. View Article : Google Scholar : PubMed/NCBI
19	Chen X, Vega VB and Ng HH: Transcriptional regulatory networks in embryonic stem cells. Cold Spring Harb Symp Quant Biol. 73:203–209. 2008. View Article : Google Scholar : PubMed/NCBI
20	Han SX, Wang JL, Guo XJ, He CC, Ying X, Ma JL, Zhang YY, Zhao Q and Zhu Q: Serum SALL4 is a novel prognosis biomarker with tumor recurrence and poor survival of patients in hepatocellular carcinoma. J Immunol Res. 2014:2623852014. View Article : Google Scholar : PubMed/NCBI
21	Deng G, Zhu L, Huang F, Nie W, Huang W, Xu H, Zheng S, Yi Z and Wan T: SALL4 is a novel therapeutic target in intrahepatic cholangiocarcinoma. Oncotarget. 6:27416–27426. 2015. View Article : Google Scholar : PubMed/NCBI
22	Forghanifard MM, Khales Ardalan S, Javdani-Mallak A, Rad A, Farshchian M and Abbaszadegan MR: Stemness state regulators SALL4 and SOX2 are involved in progression and invasiveness of esophageal squamous cell carcinoma. Med Oncol. 31:9222014. View Article : Google Scholar : PubMed/NCBI
23	Zhang L, Xu Z, Xu X, Zhang B, Wu H, Wang M, Zhang X, Yang T, Cai J, Yan Y, et al: SALL4, a novel marker for human gastric carcinogenesis and metastasis. Oncogene. 33:5491–5500. 2014. View Article : Google Scholar : PubMed/NCBI
24	Kobayashi D, Kuribayashi K, Tanaka M and Watanabe N: Overexpression of SALL4 in lung cancer and its importance in cell proliferation. Oncol Rep. 26:965–970. 2011.PubMed/NCBI
25	Oikawa T, Kamiya A, Zeniya M, Chikada H, Hyuck AD, Yamazaki Y, Wauthier E, Tajiri H, Miller LD, Wang XW, et al: Sal-like protein 4 (SALL4), a stem cell biomarker in liver cancers. Hepatology. 57:1469–1483. 2013. View Article : Google Scholar : PubMed/NCBI
26	Zhang L, Yan Y, Jiang Y, Cui Y, Zou Y, Qian J, Luo C, Lu Y and Wu X: The expression of SALL4 in patients with gliomas: High level of SALL4 expression is correlated with poor outcome. J Neurooncol. 121:261–268. 2015. View Article : Google Scholar : PubMed/NCBI
27	He J, Zhang W, Zhou Q, Zhao T, Song Y, Chai L and Li Y: Low-expression of microRNA-107 inhibits cell apoptosis in glioma by upregulation of SALL4. Int J Biochem Cell Biol. 45:1962–1973. 2013. View Article : Google Scholar : PubMed/NCBI