Long non‑coding RNA ferritin heavy polypeptide 1 pseudogene 3 controls glioma cell proliferation and apoptosis via regulation of the microRNA‑224‑5p/tumor protein D52 axis

Zhang,Yongqiang; Li,Ying; Wang,Jing; Lei,Ping

doi:10.3892/mmr.2018.9491

November-2018 Volume 18 Issue 5

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November-2018 Volume 18 Issue 5

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Article Open Access

Long non‑coding RNA ferritin heavy polypeptide 1 pseudogene 3 controls glioma cell proliferation and apoptosis via regulation of the microRNA‑224‑5p/tumor protein D52 axis

Authors:
- Yongqiang Zhang
- Ying Li
- Jing Wang
- Ping Lei
View Affiliations / Copyright

Affiliations: Geriatric Ward of Neurology, Department of Geriatrics, Institute of Tianjin Geriatrics, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China, Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China

Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Pages: 4239-4246
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Published online on: September 14, 2018

https://doi.org/10.3892/mmr.2018.9491
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Abstract

The aim of the present study was to investigate the potential role and regulatory mechanism of long non‑coding RNA ferritin heavy polypeptide 1 pseudogene 3 (FTH1P3) in glioma development. The expression of FTH1P3 in low‑ and high‑grade glioma tissues was investigated using reverse transcription‑quantitative polymerase chain reaction. FTH1P3 expression was overexpressed or suppressed in U251 glioma cells to examine the involvement of FTH1P3 in glioma cell proliferation and apoptosis using MTT assay and flow cytometry respectively. In addition, the regulatory association between FTH1P3, microRNA (miR)‑224‑5p and tumor protein (TP) D52 was investigated to elucidate the potential underlying mechanisms of FTH1P3 in glioma by luciferase reporter assay. The results revealed that FTH1P3 was up‑regulated in glioma tissues, and FTH1P3 expression in high‑grade glioma tissues was significantly higher compared with that in low‑grade glioma tissues. Upregulation of FTH1P3 promoted glioma cell proliferation and inhibited apoptosis. Furthermore, FTH1P3 inhibited miR‑224‑5p expression, which in turn negatively regulated TPD52 expression. Overexpression of miR‑224‑5p significantly inhibited U251 cell proliferation and induced cellular apoptosis; this effect was clearly reversed following co‑transfection of miR‑224‑5p and TPD52. These data revealed that upregulation of FTH1P3 may have promoted glioma cell proliferation and inhibited apoptosis. Thus, the miR‑224‑5p/TPD52 axis may be a downstream mechanism of FTH1P3 in glioma progression. The findings of the present study may provide a theoretical basis for the study of the treatment of glioma in the future.

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1	Omuro A and DeAngelis LM: Glioblastoma and other malignant gliomas: A clinical review. Jama. 310:1842–1850. 2013. View Article : Google Scholar : PubMed/NCBI
2	Gallego O: Nonsurgical treatment of recurrent glioblastoma. Curr Oncol. 22:e273–e281. 2015. View Article : Google Scholar : PubMed/NCBI
3	Rao JS: Molecular mechanisms of glioma invasiveness: The role of proteases. Nat Rev Cancer. 3:489–501. 2003. View Article : Google Scholar : PubMed/NCBI
4	Shi X, Sun M, Liu H, Yao Y and Song Y: Long non-coding RNAs: A new frontier in the study of human diseases. Cancer Lett. 339:159–166. 2013. View Article : Google Scholar : PubMed/NCBI
5	Iyer MK, Niknafs YS, Malik R, Singhal U, Sahu A, Hosono Y, Barrette TR, Prensner JR, Evans JR, Zhao S, et al: The landscape of long noncoding RNAs in the human transcriptome. Nat Genet. 47:199–208. 2015. View Article : Google Scholar : PubMed/NCBI
6	Boon RA, Jaé N, Holdt L and Dimmeler S: Long Noncoding RNAs: From Clinical Genetics to Therapeutic Targets. J Am Coll Cardiol. 67:1214–1226. 2016. View Article : Google Scholar : PubMed/NCBI
7	Chen X, Fan S and Song E: Noncoding RNAs: New players in cancers. Adv Exp Med Biol. 927:1–14. 2016. View Article : Google Scholar : PubMed/NCBI
8	Martens-Uzunova ES, Böttcher R, Croce CM, Jenster G, Visakorpi T and Calin GA: Long noncoding RNA in prostate, bladder and kidney cancer. Eur Urol. 65:1140–1151. 2014. View Article : Google Scholar : PubMed/NCBI
9	Huarte M: The emerging role of lncRNAs in cancer. Nat Med. 21:1253–1261. 2015. View Article : Google Scholar : PubMed/NCBI
10	Yan X, Hu Z, Feng Y, Hu X, Yuan J, Zhao SD, Zhang Y, Yang L, Shan W, He Q, et al: Comprehensive genomic characterization of long non-coding RNAs across human cancers. Cancer Cell. 28:529–540. 2015. View Article : Google Scholar : PubMed/NCBI
11	Fatima R, Akhade VS, Pal D and Rao SM: Long noncoding RNAs in development and cancer: Potential biomarkers and therapeutic targets. Mol Cell Ther. 3:52015. View Article : Google Scholar : PubMed/NCBI
12	Ma KX, Wang HJ, Li XR, Li T, Su G, Yang P and Wu JW: Long noncoding RNA MALAT1 associates with the malignant status and poor prognosis in glioma. Tumor Biol. 36:3355–3359. 2015. View Article : Google Scholar
13	Wang Q, Zhang J, Liu Y, Zhang W, Zhou J, Duan R, Pu P, Kang C and Han L: A novel cell cycle-associated lncRNA, HOXA11-AS, is transcribed from the 5-prime end of the HOXA transcript and is a biomarker of progression in glioma. Cancer Lett. 373:251–259. 2016. View Article : Google Scholar : PubMed/NCBI
14	Yao Y, Ma J, Xue Y, Wang P, Li Z, Liu J, Chen L, Xi Z, Teng H, Wang Z, et al: Knockdown of long non-coding RNA XIST exerts tumor-suppressive functions in human glioblastoma stem cells by up-regulating miR-152. Cancer Lett. 359:75–86. 2015. View Article : Google Scholar : PubMed/NCBI
15	Jiang X, Yan Y, Hu M, Chen X, Wang Y, Dai Y, Wu D, Wang Y, Zhuang Z and Xia H: Increased level of H19 long noncoding RNA promotes invasion, angiogenesis and stemness of glioblastoma cells. J Neurosurg. 124:129–136. 2016. View Article : Google Scholar : PubMed/NCBI
16	Zhang CZ: Long non-coding RNA FTH1P3 facilitates oral squamous cell carcinoma progression by acting as a molecular sponge of miR-224-5p to modulate fizzled 5 expression. Gene. 607:47–55. 2017. View Article : Google Scholar : PubMed/NCBI
17	Zheng X, Tang H, Zhao X, Sun Y, Jiang Y and Liu Y: Long non-coding RNA FTH1P3 facilitates uveal melanoma cell growth and invasion through miR-224-5p. PLoS One. 12:e01847462017. View Article : Google Scholar : PubMed/NCBI
18	Goto Y, Nishikawa R, Kojima S, Chiyomaru T, Enokida H, Inoguchi S, Kinoshita T, Fuse M, Sakamoto S, Nakagawa M, et al: Tumour-suppressive microRNA-224 inhibits cancer cell migration and invasion via targeting oncogenic TPD52 in prostate cancer. Febs Lett. 588:1973–1982. 2014. View Article : Google Scholar : PubMed/NCBI
19	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
20	Xia M, Wei J and Tong K: MiR-224 promotes proliferation and migration of gastric cancer cells through targeting PAK4. Pharmazie. 71:460–464. 2016.PubMed/NCBI
21	Zhang GJ, Zhou H, Xiao H, Li Y and Zhou T: Up-regulation of miR-224 promotes cancer cell proliferation and invasion and predicts relapse of colorectal cancer. Cancer Cell Int. 13:1042013. View Article : Google Scholar : PubMed/NCBI
22	Zhao H, Bi T, Qu Z, Jiang J, Cui S and Wang Y: Expression of miR-224-5p is associated with the original cisplatin resistance of ovarian papillary serous carcinoma. Oncol Rep. 32:1003–1012. 2014. View Article : Google Scholar : PubMed/NCBI
23	Lu S, Wang S, Geng S, Ma S, Liang Z and Jiao B: Upregulation of microRNA-224 confers a poor prognosis in glioma patients. Clin Transl Oncol. 15:569–574. 2013. View Article : Google Scholar : PubMed/NCBI
24	Byrne JA, Tomasetto C, Garnier JM, Rouyer N, Mattei MG, Bellocq JP, Rio MC and Basset P: A screening method to identify genes commonly overexpressed in carcinomas and the identification of a novel complementary DNA sequence. Cancer Res. 55:2896–2903. 1995.PubMed/NCBI
25	Byrne JA, Frost S, Chen Y and Bright RK: Tumor protein D52 (TPD52) and cancer-oncogene understudy or understudied oncogene? Tumor Biol. 35:7369–7382. 2014. View Article : Google Scholar
26	Moritz T, Venz S, Junker H, Kreuz S, Walther R and Zimmermann U: Isoform 1 of TPD52 (PC-1) promotes neuroendocrine transdifferentiation in prostate cancer cells. Tumor Biol. 37:10435–10446. 2016. View Article : Google Scholar
27	Ummanni R, Teller S, Junker H, Zimmermann U, Venz S, Scharf C, Giebel J and Walther R: Altered expression of tumor protein D52 regulates apoptosis and migration of prostate cancer cells. FEBS J. 275:5703–5713. 2008. View Article : Google Scholar : PubMed/NCBI
28	Zhao Z, Liu H, Hou J, Li T, Du X, Zhao X, Xu W, Xu W and Chang J: Tumor protein D52 (TPD52) inhibits growth and metastasis in renal cell carcinoma cells through the PI3K/Akt signaling pathway. Oncol Res. 25:773–779. 2017. View Article : Google Scholar : PubMed/NCBI
29	Wang Y, Chen CL, Pan QZ, Wu YY, Zhao JJ, Jiang SS, Chao J, Zhang XF, Zhang HX, Zhou ZQ, et al: Decreased TPD52 expression is associated with poor prognosis in primary hepatocellular carcinoma. Oncotarget. 7:63232016.PubMed/NCBI
30	Kumamoto T, Seki N, Mataki H, et al: Tumor-Suppressive MicroRNA-218 Inhibits Cancer Cell Migration And Invasion Directly Targeting TPD52 In Lung Squamous Cell Carcinoma. A71. Oncogenes and Angiogenesis In Lung Tumors. Am Thoracic Soc. A23712017.
31	Li G, Yao L, Zhang J, Li X, Dang S, Zeng K, Zhou Y and Gao F: Tumor-suppressive microRNA-34a inhibits breast cancer cell migration and invasion via targeting oncogenic TPD52. Tumor Biol. 37:7481–7491. 2016. View Article : Google Scholar