miR‑204 functions as a tumor suppressor gene, at least partly by suppressing CYP27A1 in glioblastoma

Xin,Jun; Zheng,Li‑Min; Sun,De‑Ke; Li,Xian‑Feng; Xu,Peng; Tian,Li‑Qiang

doi:10.3892/ol.2018.8846

miR‑204 functions as a tumor suppressor gene, at least partly by suppressing CYP27A1 in glioblastoma

Authors:
- Jun Xin
- Li‑Min Zheng
- De‑Ke Sun
- Xian‑Feng Li
- Peng Xu
- Li‑Qiang Tian
View Affiliations

Affiliations: Department of Neurosurgery, Yishui Central Hospital, Linyi, Shandong 276400, P.R. China, Department of Neurosurgery, Tai'an Central Hospital, Tai'an, Shandong 271000, P.R. China, Department of Neurosurgery, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China
Published online on: May 30, 2018 https://doi.org/10.3892/ol.2018.8846
Pages: 1439-1448
Copyright: © Xin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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

Gliomas are the most common type of malignant primary brain tumors in adults and exhibit a spectrum of aberrantly aggressive phenotypes. Despite advances in treatments during past decades, prognosis of the disease remains poor, with a median survival time of 12‑14 months. Future studies on the molecular mechanism of the disease may provide the theoretical basis to identify new targets for effective therapies. The present study revealed that in glioblastoma cells, the overexpression of cytochrome P450, family 27, subfamily A, polypeptide 1 (CYP27A1) promoted proliferation, while silencing of CYP27A1 inhibited proliferation, without affecting migration and invasion. CYP27A1 protein was upregulated in glioblastoma tissues, indicating that CYP27A1 is an oncogene. The downregulation of specific microRNAs (miRNA) may contribute to the upregulation of oncogenes in glioblastoma. A common strategy was used to predict target miRNAs of CPY27A1 using the miRanda algorithm. miR‑211 and miR‑204 could target the 3'untranslated region of CPY27A1 mRNA. Additional studies confirmed that the overexpression of miR‑204 inhibited CPY27A1 expression in glioblastoma cells. Finally, it was identified that miR‑204 was downregulated in glioblastoma and that its overexpression inhibited proliferation, migration and invasion in glioblastoma cells. Thus, it was concluded that miR‑204 functions as a tumor suppressor gene, at least partly by suppressing CYP27A1 in glioblastoma.

View Figures

View References

1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2018. CA Cancer J Clin. 68:7–30. 2018. View Article : Google Scholar : PubMed/NCBI
2	Das S and Marsden PA: Angiogenesis in glioblastoma. N Engl J Med. 369:1561–1563. 2013. View Article : Google Scholar : PubMed/NCBI
3	Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, et al: Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 10:459–466. 2009. View Article : Google Scholar : PubMed/NCBI
4	Nelson ER, Wardell SE, Jasper JS, Park S, Suchindran S, Howe MK, Carver NJ, Pillai RV, Sullivan PM, Sondhi V, et al: 27-Hydroxycholesterol links hypercholesterolemia and breast cancer pathophysiology. Science. 342:1094–1098. 2013. View Article : Google Scholar : PubMed/NCBI
5	Norlin M, von Bahr S, Björkhem I and Wikvall K: On the substrate specificity of human CYP27A1: Implications for bile acid and cholestanol formation. J Lipid Res. 44:1515–1522. 2003. View Article : Google Scholar : PubMed/NCBI
6	Lu DL, Sookthai D, Le Cornet C, Katzke VA, Johnson TS, Kaaks R and Fortner RT: Reproducibility of serum oxysterols and lanosterol among postmenopausal women: Results from EPIC-Heidelberg. Clin Biochem. 52:117–122. 2018. View Article : Google Scholar : PubMed/NCBI
7	Björkhem I: Mechanism of degradation of the steroid side chain in the formation of bile acids. J Lipid Res. 33:455–471. 1992.PubMed/NCBI
8	Russell DW and Setchell KD: Bile acid biosynthesis. Biochemistry. 31:4737–4749. 1992. View Article : Google Scholar : PubMed/NCBI
9	Lee RC, Feinbaum RL and Ambros V: The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 75:843–854. 1993.
10	Chan JA, Krichevsky AM and Kosik KS: MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res. 65:6029–6033. 2005. View Article : Google Scholar : PubMed/NCBI
11	Mao J, Zhang M, Zhong M, Zhang Y and Lv K: MicroRNA-204, a direct negative regulator of ezrin gene expression, inhibits glioma cell migration and invasion. Mol Cell Biochem. 396:117–128. 2014. View Article : Google Scholar : PubMed/NCBI
12	Kefas B, Godlewski J, Comeau L, Li Y, Abounader R, Hawkinson M, Lee J, Fine H, Chiocca EA, Lawler S and Purow B: microRNA-7 inhibits the epidermal growth factor receptor and the Akt pathway and is down-regulated in glioblastoma. Cancer Res. 68:3566–3572. 2008. View Article : Google Scholar : PubMed/NCBI
13	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
14	Matusiak D and Benya RV: CYP27A1 and CYP24 expression as a function of malignant transformation in the colon. J Histochem Cytochem. 55:1257–1264. 2007. View Article : Google Scholar : PubMed/NCBI
15	Lu Z, Liu M, Stribinskis V, Klinge CM, Ramos KS, Colburn NH and Li Y: MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene. Oncogene. 27:4373–4379. 2008. View Article : Google Scholar : PubMed/NCBI
16	Zhu S, Wu H, Wu F, Nie D, Sheng S and Mo YY: MicroRNA-21 targets tumor suppressor genes in invasion and metastasis. Cell Res. 18:350–359. 2008. View Article : Google Scholar : PubMed/NCBI
17	Gangemi RM, Griffero F, Marubbi D, Perera M, Capra MC, Malatesta P, Ravetti GL, Zona GL, Daga A and Corte G: SOX2 silencing in glioblastoma tumor-initiating cells causes stop of proliferation and loss of tumorigenicity. Stem Cells. 27:40–48. 2009. View Article : Google Scholar : PubMed/NCBI
18	Lee Y, Yang X, Huang Y, Fan H, Zhang Q, Wu Y, Li J, Hasina R, Cheng C, Lingen MW, et al: Network modeling identifies molecular functions targeted by miR-204 to suppress head and neck tumor metastasis. PLoS Comput Biol. 6:e10007302010. View Article : Google Scholar : PubMed/NCBI
19	Mikhaylova O, Stratton Y, Hall D, Kellner E, Ehmer B, Drew AF, Gallo CA, Plas DR, Biesiada J, Meller J and Czyzyk-Krzeska MF: VHL-regulated MiR-204 suppresses tumor growth through inhibition of LC3B-mediated autophagy in renal clear cell carcinoma. Cancer Cell. 21:532–546. 2012. View Article : Google Scholar : PubMed/NCBI
20	Ying Z, Li Y, Wu J, Zhu X, Yang Y, Tian H, Li W, Hu B, Cheng SY and Li M: Loss of miR-204 expression enhances glioma migration and stem cell-like phenotype. Cancer Res. 73:990–999. 2013. View Article : Google Scholar : PubMed/NCBI
21	Sacconi A, Biagioni F, Canu V, Mori F, Di Benedetto A, Lorenzon L, Ercolani C, Di Agostino S, Cambria AM, Germoni S, et al: miR-204 targets Bcl-2 expression and enhances responsiveness of gastric cancer. Cell Death Dis. 3:e4232012. View Article : Google Scholar : PubMed/NCBI
22	Zhang L, Wang X and Chen P: miR-204 down regulates SIRT1 and reverts SIRT1-induced epithelial-mesenchymal transition, anoikis resistance and invasion in gastric cancer cells. BMC Cancer. 13:2902013. View Article : Google Scholar : PubMed/NCBI
23	Chung TK, Lau TS, Cheung TH, Yim SF, Lo KW, Siu NS, Chan LK, Yu MY, Kwong J, Doran G, et al: Dysregulation of microRNA-204 mediates migration and invasion of endometrial cancer by regulating FOXC1. Int J Cancer. 130:1036–1045. 2012. View Article : Google Scholar : PubMed/NCBI
24	Ryan J, Tivnan A, Fay J, Bryan K, Meehan M, Creevey L, Lynch J, Bray IM, O'Meara A, Tracey L, et al: MicroRNA-204 increases sensitivity of neuroblastoma cells to cisplatin and is associated with a favourable clinical outcome. Br J Cancer. 107:967–976. 2012. View Article : Google Scholar : PubMed/NCBI
25	Allen M, Bjerke M, Edlund H, Nelander S and Westermark B: Origin of the U87MG glioma cell line: Good news and bad news. Sci Transl Med. 8:354re32016. View Article : Google Scholar : PubMed/NCBI