Downregulation of microRNA‑3934‑5p induces apoptosis and inhibits the proliferation of neuroblastoma cells by targeting TP53INP1

Ye,Wei; Liang,Fulv; Ying,Chen; Zhang,Maolin; Feng,Dongbo; Jiang,Xinyu

doi:10.3892/etm.2019.8007

Downregulation of microRNA‑3934‑5p induces apoptosis and inhibits the proliferation of neuroblastoma cells by targeting TP53INP1

Authors:
- Wei Ye
- Fulv Liang
- Chen Ying
- Maolin Zhang
- Dongbo Feng
- Xinyu Jiang
View Affiliations

Affiliations: Department of Neurology, Jianou Municipal Hospital, Jianou, Fujian 353100, P.R. China, Department of Urology, The Third Hospital of Xiamen, Xiamen, Fujian 361000, P.R. China, Department of Urology, Haicang Hospital of Xiamen, Xiamen, Fujian 361026, P.R. China, Department of Surgery, Xiapu County Hospital, Xiapu County, Ningde, Fujian 355100, P.R. China, Department of Sports Medicine, The Central Hospital of Yongzhou, Yongzhou, Hunan 425000, P.R. China, Department of General Surgery, Xiamen Maternity and Child Health Care Hospital, Xiamen, Fujian 361000, P.R. China
Published online on: September 13, 2019 https://doi.org/10.3892/etm.2019.8007
Pages: 3729-3736
Copyright: © Ye 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

Neuroblastoma is the most common pediatric extracranial solid tumour in the world. miRNAs are a group of endogenous small non‑coding RNAs that act on target genes to serve critical roles in many biological processes. Presently, the expression and role of miR‑3934‑5p in neuroblastoma remains unclear. Therefore, the aim of the present study was to investigate the expression of miR‑3934‑5p in neuroblastoma tissues and cell lines and to assess the role of miR‑3934‑5p in neuroblastoma. In the current study, the results revealed that miR‑3934‑5p was significantly upregulated in neuroblastoma tissues and cell lines. The data also identified TP53INP1 as a direct target gene of miR‑3934‑5p, which was negatively regulated by miR‑3934‑5p. The present study further demonstrated that TP53INP1 was downregulated in both neuroblastoma tissues and cell lines. Furthermore, the results of the current study indicate that miR‑3934‑5p downregulation may induce apoptosis and inhibit neuroblastoma cell viability. However, these effects were reversed via TP53INP1‑siRNA. Data from the current study indicates that the miR‑3934‑5p/TP53INP1 axis may be a novel therapeutic target for neuroblastoma treatment.

View Figures

View References

1	Health Professional Version, . Neuroblastoma Treatment (PDQ^®)-Health Professional VersionNational Cancer Institute; Bethesda, MD: 2014, https://www.cancer.gov/types/neuroblastoma/hp/neuroblastoma-treatment-pdq
2	Gatta G, Botta L, Rossi S, Aareleid T, Bielska-Lasota M, Clavel J, Dimitrova N, Jakab Z, Kaatsch P, Lacour B, et al: Childhood cancer survival in Europe 1999–2007: Results of EUROCARE-5-a population-based study. Lancet Oncol. 15:35–47. 2014. View Article : Google Scholar : PubMed/NCBI
3	Brodeur GM and Bagatell R: Mechanisms of neuroblastoma regression. Nat Rev Clin Oncol. 11:704–713. 2014. View Article : Google Scholar : PubMed/NCBI
4	Li P, Gao Y, Ji Z, Zhang X, Xu Q, Li G, Guo Z, Zheng B and Guo X: Role of urokinase plasminogen activator and its receptor in metastasis and invasion of neuroblastoma. J Pediatr Surg. 39:1512–1519. 2004. View Article : Google Scholar : PubMed/NCBI
5	Matthay KK, Maris JM, Schleiermacher G, Nakagawara A, Mackall CL, Diller L and Weiss WA: Neuroblastoma. Nat Rev Dis Primers. 2:160782016. View Article : Google Scholar : PubMed/NCBI
6	Mazar J, Li Y, Rosado A, Phelan P, Kedarinath K, Parks GD, Alexander KA and Westmoreland TJ: Zika virus as an oncolytic treatment of human neuroblastoma cells requires CD24. PLoS One. 13:e02003582018. View Article : Google Scholar : PubMed/NCBI
7	Smith MA, Altekruse SF, Adamson PC, Reaman GH and Seibel NL: Declining childhood and adolescent cancer mortality. Cancer. 120:2497–2506. 2014. View Article : Google Scholar : PubMed/NCBI
8	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
9	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
10	Kwon C, Han Z, Olson EN and Srivastava D: MicroRNA1 influences cardiac differentiation in Drosophila and regulates Notch signaling. Proc Natl Acad Sci USA. 102:18986–18991. 2005. View Article : Google Scholar : PubMed/NCBI
11	Ro S, Park C, Young D, Sanders KM and Yan W: Tissue-dependent paired expression of miRNAs. Nucleic Acids Res. 35:5944–5953. 2007. View Article : Google Scholar : PubMed/NCBI
12	Mallory AC and Vaucheret H: MicroRNAs: Something important between the genes. Curr Opin Plant Biol. 7:120–125. 2004. View Article : Google Scholar : PubMed/NCBI
13	Garzon R, Calin GA and Croce CM: MicroRNAs in cancer. Annu Rev Med. 60:167–179. 2009. View Article : Google Scholar : PubMed/NCBI
14	Ambros V: microRNAs: Tiny regulators with great potential. Cell. 107:823–826. 2001. View Article : Google Scholar : PubMed/NCBI
15	Carrington JC and Ambros V: Role of microRNAs in plant and animal development. Science. 301:336–338. 2001. View Article : Google Scholar
16	Chen JY, Yao DS, He CJ, et al: Differential expression of microRNA in cervical squamous cell carcinoma. J Pract Med. 30:83–87. 2014.
17	Sathipati SY and Ho SY: Identifying the miRNA signature associated with survival time in patients with lung adenocarcinoma using miRNA expression profiles. Sci Rep. 7:2017.
18	Chen Q, Zhou Y, Richards AM and Wang P: Up-regulation of miRNA-221 inhibits hypoxia/reoxygenation-induced autophagy through the DDIT4/mTORC1 and Tp53inp1/p62 pathways. Biochem Biophys Res Commun. 474:168–174. 2016. View Article : Google Scholar : PubMed/NCBI
19	Xu CG, Yang MF, Fan JX and Wang W: MiR-30a and miR-205 are downregulated in hypoxia and modulate radiosensitivity of prostate cancer cells by inhibiting autophagy via TP53INP1. Eur Rev Med Pharmacol Sci. 20:1501–1508. 2016.PubMed/NCBI
20	Wang W, Liu J and Wu Q: MiR-205 suppresses autophagy and enhances radiosensitivity of prostate cancer cells by targeting TP53INP1. Eur Rev Med Pharmacol Sci. 20:92–100. 2016.PubMed/NCBI
21	Seillier M, Peuget S, Gayet O, Gauthier C, NGuessan P, Monte M, Carrier A, Iovanna JL and Dusetti NJ: TP53INP1, a tumor suppressor, interacts with LC3 and ATG8-family proteins through the LC3-interacting region (LIR) and promotes autophagy-dependent cell death. Cell Death Differ. 19:1525–1535. 2012. View Article : Google Scholar : PubMed/NCBI
22	Saadi H, Seillier M and Carrier A: The stress protein TP53INP1 plays a tumor suppressive role by regulating metabolic homeostasis. Biochimie. 118:44–50. 2015. View Article : Google Scholar : PubMed/NCBI
23	Xue X, Wang X, Zhao Y, Hu R and Qin L: Exosomal miR-93 promotes proliferation and invasion in hepatocellular carcinoma by directly inhibiting TIMP2/TP53INP1/CDKN1A. Biochem Biophys Res Commun. 502:515–521. 2018. View Article : Google Scholar : PubMed/NCBI
24	Wang Y, Sun H, Zhang D, Fan D, Zhang Y, Dong X, Liu S, Yang Z, Ni C, Li Y, et al: TP53INP1 inhibits hypoxia-induced vasculogenic mimicry formation via the ROS/snail signalling axis in breast cancer. J Cell Mol Med. 22:3475–3488. 2018. View Article : Google Scholar : PubMed/NCBI
25	Cai Q, Zeng S, Dai X, Wu J and Ma W: miR-504 promotes tumour growth and metastasis in human osteosarcoma by targeting TP53INP1. Oncol Rep. 38:2993–3000. 2017. View Article : Google Scholar : PubMed/NCBI
26	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
27	Yu X, Li Z, Shen J, Wu WK, Liang J, Weng X and Qiu G: MicroRNA-10b promotes nucleus pulposus cell proliferation through RhoC-Akt pathway by targeting HOXD10 in intervetebral disc degeneration. PLoS One. 8:e830802013. View Article : Google Scholar : PubMed/NCBI
28	Li Z, Yu X, Shen J, Wu WK and Chan MT: MicroRNA expression and its clinical implications in Ewings sarcoma. Cell Prolif. 48:1–6. 2015. View Article : Google Scholar : PubMed/NCBI
29	Yu X and Li Z: MicroRNAs regulate vascular smooth muscle cell functions in atherosclerosis (review). Int J Mol Med. 34:923–933. 2014. View Article : Google Scholar : PubMed/NCBI
30	Li M, Yu M, Liu C, Zhu H, He X, Peng S and Hua J: miR-34c works downstream of p53 leading to dairy goat male germline stem-cell (mGSCs) apoptosis. Cell Prolif. 46:223–231. 2013. View Article : Google Scholar : PubMed/NCBI
31	Wang Z, Wang N, Liu P, Chen Q, Situ H, Xie T, Zhang J, Peng C, Lin Y and Chen J: MicroRNA-25 regulates chemoresistance-associat-ed autophagy in breast cancer cells, a process modulated by the natural autophagy inducer isoliquiritigenin. Oncotarget. 5:7013–7026. 2014.PubMed/NCBI
32	Dong R, Liu X, Zhang Q, Jiang Z, Li Y, Wei Y, Li Y, Yang Q, Liu J, Wei JJ, et al: miR-145 inhibits tumor growth and metastasis by targeting metadherin in high-grade serous ovarian carcinoma. Oncotarget. 5:10816–10829. 2014. View Article : Google Scholar : PubMed/NCBI
33	Li Z, Lei H, Luo M, Wang Y, Dong L, Ma Y, Liu C, Song W, Wang F, Zhang J, et al: DNA methylation downregulated mir-10b acts as a tumor suppressor in gastric cancer. Gastric Cancer. 18:43–54. 2015. View Article : Google Scholar : PubMed/NCBI
34	Li Z, Yu X, Wang Y, Shen J, Wu WK, Liang J and Feng F: By downregulating TIAM1 expression, microRNA-329 suppresses gastric cancer invasion and growth. Oncotarget. 6:17559–17569. 2015.PubMed/NCBI
35	Li Z, Yu X, Shen J and Jiang Y: MicroRNA dysregulation in uveal melanoma: A new player enters the game. Oncotarget. 6:4562–4568. 2015.PubMed/NCBI
36	Li J, You T and Jing J: MiR-125b inhibits cell biological progression of Ewings sarcoma by suppressing the PI3K/Akt signalling pathway. Cell Prolif. 47:152–160. 2014. View Article : Google Scholar : PubMed/NCBI
37	Schirmer U, Doberstein K, Rupp AK, Bretz NP, Wuttig D, Kiefel H, Breunig C, Fiegl H, Müller-Holzner E, Zeillinger R, et al: Role of miR-34a as a suppressor of L1CAM in endometrial carcinoma. Oncotarget. 5:462–472. 2014. View Article : Google Scholar : PubMed/NCBI
38	Jiang PH, Motoo Y, Garcia S, Iovanna JL, Pébusque MJ and Sawabu N: Down-expression of tumor protein p53-induced nuclear protein 1 in human gastric cancer. World J Gastroenterol. 12:691–696. 2006. View Article : Google Scholar : PubMed/NCBI
39	Tomasini R, Samir AA, Carrier A, Isnardon D, Cecchinelli B, Soddu S, Malissen B, Dagorn JC, Iovanna JL and Dusetti NJ: TP53INP1s and homeodomain-interacting protein kinase-2 (HIPK2) are partners in regulating p53 activity. J Biol Chem. 278:37722–37729. 2003. View Article : Google Scholar : PubMed/NCBI
40	Liao D, Li T, Ye C, Zeng L, Li H, Pu X, Ding C, He Z and Huang GL: miR-221 inhibits autophagy and targets TP53INP1 in colorectal cancer cells. Exp Ther Med. 15:1712–1717. 2018.PubMed/NCBI
41	Ma S, Tang KH, Chan YP, Lee TK, Kwan PS, Castilho A, Ng I, Man K, Wong N, To KF, et al: miR-130b Promotes CD133(+) liver tumor-initiating cell growth and self-renewal via tumor protein 53-induced nuclear protein 1. Cell Stem Cell. 7:694–707. 2010. View Article : Google Scholar : PubMed/NCBI
42	Jiang F, Liu T, He Y, Yan Q, Chen X, Wang H and Wan X: MiR-125b promotes proliferation and migration of type II endometrial carcinoma cells through targeting TP53INP1 tumor suppressor in vitro and in vivo. BMC Cancer. 11:4252011. View Article : Google Scholar : PubMed/NCBI
43	Seux M, Peuget S, Montero MP, Siret C, Rigot V, Clerc P, Gigoux V, Pellegrino E, Pouyet L, NGuessan P, et al: TP53INP1 decreases pancreatic cancer cell migration by regulating SPARC expression. Oncogene. 30:3049–3061. 2011. View Article : Google Scholar : PubMed/NCBI
44	Giusiano S, Baylot V, Andrieu C, Fazli L, Gleave M, Iovanna JL, Taranger-Charpin C, Garcia S and Rocchi P: TP53INP1 as new therapeutic target in castration-resistant prostate cancer. Prostate. 72:1286–1294. 2012. View Article : Google Scholar : PubMed/NCBI
45	Gironella M, Seux M, Xie MJ, Cano C, Tomasini R, Gommeaux J, Garcia S, Nowak J, Yeung ML, Jeang KT, et al: Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development. Proc Natl Acad Sci USA. 104:16170–16175. 2007. View Article : Google Scholar : PubMed/NCBI
46	Chaluvally-Raghavan P, Zhang F, Pradeep S, Hamilton MP, Zhao X, Rupaimoole R, Moss T, Lu Y, Yu S, Pecot CV, et al: Copy number gain of hsa-miR-569 at 3q26.2 leads to loss of TP53INP1 and aggressiveness of epithelial cancers. Cancer Cell. 26:863–879. 2014. View Article : Google Scholar : PubMed/NCBI