MiR-103/miR-195/miR-15b Regulate SALL4 and Inhibit Proliferation and Migration in Glioma

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2018 Nov 15

PMID 30423818

Citations 34

Authors

Li-Ping Chen

Na-Na Zhang

Xue-Qing Ren

Jie He

Yu Li

Affiliations

Soon will be listed here.

Abstract

Glioma is the common highly malignant primary brain tumor. However, the molecular pathways that result in the pathogenesis of glioma remain elusive. In this study, we found that microRNA-103 (miR-103), microRNA-195 (miR-195), or microRNA-15b (miR-15b), which all have the same 5' "seed" miRNA portion and share common binding sites in the SALL4 3'-untranslated region (UTR), were downregulated in glioma tissues and cell lines. These miRNAs suppressed glioma cell proliferation, migration, and invasion, induced cell apoptosis, and decreased the level of the SALL4 protein, but not that of SALL4 mRNA, which was identified as a direct target of all three miRNAs. The caspase-3/7 activity expression in U251 cells overexpressing these miRNAs was rescued during SALL4 upregulation. An obvious inverse correlation was observed between SALL4 and miR-103 or miR-195 expression levels in clinical glioma samples. Moreover, enforced expression of SALL4 stimulated cell proliferation, migration, and invasion. In conclusion, these data suggest that miR-103, miR-195, and miR-15b post-transcriptionally downregulated the expression of SALL4 and suppressed glioma cell growth, migration, and invasion, and increased cell apoptosis. These results provide a potential therapeutic target that may downregulate SALL4 in glioma.

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References

Ueno S, Lu J, He J, Li A, Zhang X, Ritz J . Aberrant expression of SALL4 in acute B cell lymphoblastic leukemia: mechanism, function, and implication for a potential novel therapeutic target. Exp Hematol. 2014; 42(4):307-316.e8. PMC: 4135469. DOI: 10.1016/j.exphem.2014.01.005. View

Jiang B, Li M, Ji F, Nie Y . MicroRNA-219 exerts a tumor suppressive role in glioma via targeting Sal-like protein 4. Exp Ther Med. 2017; 14(6):6213-6221. PMC: 5740761. DOI: 10.3892/etm.2017.5292. View

He J, Zhou M, Chen X, Yue D, Yang L, Qin G . Inhibition of SALL4 reduces tumorigenicity involving epithelial-mesenchymal transition via Wnt/β-catenin pathway in esophageal squamous cell carcinoma. J Exp Clin Cancer Res. 2016; 35(1):98. PMC: 4915037. DOI: 10.1186/s13046-016-0378-z. View

Yu D, Zhou H, Xun Q, Xu X, Ling J, Hu Y . microRNA-103 regulates the growth and invasion of endometrial cancer cells through the downregulation of tissue inhibitor of metalloproteinase 3. Oncol Lett. 2012; 3(6):1221-1226. PMC: 3392565. DOI: 10.3892/ol.2012.638. View

Yu X, Zhang Y, Cavazos D, Ma X, Zhao Z, Du L . miR-195 targets cyclin D3 and survivin to modulate the tumorigenesis of non-small cell lung cancer. Cell Death Dis. 2018; 9(2):193. PMC: 5833354. DOI: 10.1038/s41419-017-0219-9. View

Al-Baradie R, Yamada K, St Hilaire C, Chan W, Andrews C, McIntosh N . Duane radial ray syndrome (Okihiro syndrome) maps to 20q13 and results from mutations in SALL4, a new member of the SAL family. Am J Hum Genet. 2002; 71(5):1195-9. PMC: 385096. DOI: 10.1086/343821. View

Li H, Zhang J, Lee M, Yu G, Han X, Kim D . OIP5, a target of miR-15b-5p, regulates hepatocellular carcinoma growth and metastasis through the AKT/mTORC1 and β-catenin signaling pathways. Oncotarget. 2017; 8(11):18129-18144. PMC: 5392313. DOI: 10.18632/oncotarget.15185. View

Zheng Y, Xiao K, Xiao G, Tong S, Ding Y, Wang Q . MicroRNA-103 promotes tumor growth and metastasis in colorectal cancer by directly targeting LATS2. Oncol Lett. 2016; 12(3):2194-2200. PMC: 4998581. DOI: 10.3892/ol.2016.4814. View

Zhou W, Zou B, Liu L, Cui K, Gao J, Yuan S . MicroRNA-98 acts as a tumor suppressor in hepatocellular carcinoma via targeting SALL4. Oncotarget. 2016; 7(45):74059-74073. PMC: 5342035. DOI: 10.18632/oncotarget.12190. View

10.

Kobayashi D, Kuribayashi K, Tanaka M, Watanabe N . Overexpression of SALL4 in lung cancer and its importance in cell proliferation. Oncol Rep. 2011; 26(4):965-70. DOI: 10.3892/or.2011.1374. View

11.

Zheng J, Liu Y, Qiao Y, Zhang L, Lu S . miR-103 Promotes Proliferation and Metastasis by Targeting KLF4 in Gastric Cancer. Int J Mol Sci. 2017; 18(5). PMC: 5454823. DOI: 10.3390/ijms18050910. View

12.

Zhang Q, Xu H, Huang M, Ma L, Huang Q, Yao Q . MicroRNA-195 plays a tumor-suppressor role in human glioblastoma cells by targeting signaling pathways involved in cellular proliferation and invasion. Neuro Oncol. 2012; 14(3):278-87. PMC: 3280801. DOI: 10.1093/neuonc/nor216. View

13.

Fu X, Zhang W, Su Y, Lu L, Wang D, Wang H . MicroRNA-103 suppresses tumor cell proliferation by targeting PDCD10 in prostate cancer. Prostate. 2016; 76(6):543-51. DOI: 10.1002/pros.23143. View

14.

Alberti C, Manzenreither R, Sowemimo I, Burkard T, Wang J, Mahofsky K . Cell-type specific sequencing of microRNAs from complex animal tissues. Nat Methods. 2018; 15(4):283-289. PMC: 5886366. DOI: 10.1038/nmeth.4610. View

15.

Filipowicz W, Bhattacharyya S, Sonenberg N . Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?. Nat Rev Genet. 2008; 9(2):102-14. DOI: 10.1038/nrg2290. View

16.

Zhang J, Tam W, Tong G, Wu Q, Chan H, Soh B . Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1. Nat Cell Biol. 2006; 8(10):1114-23. DOI: 10.1038/ncb1481. View

17.

Zhang L, Xu Z, Xu X, Zhang B, Wu H, Wang M . SALL4, a novel marker for human gastric carcinogenesis and metastasis. Oncogene. 2013; 33(48):5491-500. DOI: 10.1038/onc.2013.495. View

18.

Negrini M, Nicoloso M, Calin G . MicroRNAs and cancer--new paradigms in molecular oncology. Curr Opin Cell Biol. 2009; 21(3):470-9. DOI: 10.1016/j.ceb.2009.03.002. View

19.

He J, Zhang W, Zhou Q, Zhao T, Song Y, Chai L . Low-expression of microRNA-107 inhibits cell apoptosis in glioma by upregulation of SALL4. Int J Biochem Cell Biol. 2013; 45(9):1962-73. DOI: 10.1016/j.biocel.2013.06.008. View

20.

Esquela-Kerscher A, Slack F . Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 2006; 6(4):259-69. DOI: 10.1038/nrc1840. View