MicroRNA‑382 inhibits cell proliferation and invasion of retinoblastoma by targeting BDNF‑mediated PI3K/AKT signalling pathway

Song,Dan; Diao,Jiandong; Yang,Yongjing; Chen,Yahong

doi:10.3892/mmr.2017.7396

November-2017 Volume 16 Issue 5

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November-2017 Volume 16 Issue 5

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Article

MicroRNA‑382 inhibits cell proliferation and invasion of retinoblastoma by targeting BDNF‑mediated PI3K/AKT signalling pathway

Authors:
- Dan Song
- Jiandong Diao
- Yongjing Yang
- Yahong Chen
View Affiliations / Copyright

Affiliations: Department of Ophthalmology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, P.R. China, Department of Oncology and Hematology, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China, Department of Thoracic Oncology, Jilin Cancer Hospital, Changchun, Jilin 130012, P.R. China, Department of Colorectal Surgery, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China
Pages: 6428-6436
|
Published online on: August 29, 2017

https://doi.org/10.3892/mmr.2017.7396
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Abstract

It has previously been demonstrated that multiple microRNAs (miRNAs or miRs) are aberrantly expressed in retinoblastoma (RB) and contribute to RB initiation and progression. miR‑382 has been revealed to be aberrantly expressed and therefore exhibits a key role in the progression of various types of cancer. However, the expression pattern, functional roles and underlying molecular mechanism of miR‑382 in RB remain unknown. The present study investigated the expression levels of miR‑382 and its effects on RB cells and the underlying regulatory mechanism of its action. It was demonstrated that miR‑382 was downregulated in RB tissues and cell lines. Upregulation of miR‑382 inhibited RB cell proliferation and invasion in vitro. Additionally, brain‑derived neurotrophic factor (BDNF) was identified as a novel target of miR‑382 in RB. BDNF was upregulated in RB tissues and negatively associated with miR‑382 expression levels. Furthermore, BDNF overexpression rescued the tumour‑suppressing effects on RB cells induced by miR‑382. miR‑382 inactivated the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signalling pathway in RB. These findings suggested that miR‑382 serves as a tumour suppressor in RB, in part, by targeting the BDNF‑mediated PI3K/AKT signalling pathway. The results of the present study suggest a potential therapeutic strategy for treating RB patients in the future.

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1	Abramson DH, Shields CL, Munier FL and Chantada GL: Treatment of retinoblastoma in 2015: Agreement and disagreement. JAMA Ophthalmol. 133:1341–1347. 2015. View Article : Google Scholar : PubMed/NCBI
2	Broaddus E, Topham A and Singh AD: Incidence of retinoblastoma in the USA: 1975–2004. Br J Ophthalmol. 93:21–23. 2009. View Article : Google Scholar : PubMed/NCBI
3	Kleinerman RA, Schonfeld SJ and Tucker MA: Sarcomas in hereditary retinoblastoma. Clin Sarcoma Res. 2:152012. View Article : Google Scholar : PubMed/NCBI
4	Marees T, Moll AC, Imhof SM, de Boer MR, Ringens PJ and van Leeuwen FE: Risk of second malignancies in survivors of retinoblastoma: More than 40 years of follow-up. J Natl Cancer Inst. 100:1771–1779. 2008. View Article : Google Scholar : PubMed/NCBI
5	Moll AC, Imhof SM, Bouter LM and Tan KE: Second primary tumors in patients with retinoblastoma. A review of the literature. Ophthalmic Genet. 18:27–34. 1997. View Article : Google Scholar : PubMed/NCBI
6	Benavente CA and Dyer MA: Genetics and epigenetics of human retinoblastoma. Annu Rev Pathol. 10:547–562. 2015. View Article : Google Scholar : PubMed/NCBI
7	Yang YQ, Li J and Yuan HF: Epidemiology and risk factors of retinoblastoma in Chongqing area. Int J Ophthalmol. 9:984–988. 2016.PubMed/NCBI
8	Finger PT, Harbour JW and Karcioglu ZA: Risk factors for metastasis in retinoblastoma. Surv Ophthalmol. 47:1–16. 2002. View Article : Google Scholar : PubMed/NCBI
9	Friedman DL, Himelstein B, Shields CL, Shields JA, Needle M, Miller D, Bunin GR and Meadows AT: Chemoreduction and local ophthalmic therapy for intraocular retinoblastoma. J Clin Oncol. 18:12–17. 2000. View Article : Google Scholar : PubMed/NCBI
10	Dimaras H, Kimani K, Dimba EA, Gronsdahl P, White A, Chan HS and Gallie BL: Retinoblastoma. Lancet. 379:1436–1446. 2012. View Article : Google Scholar : PubMed/NCBI
11	Kaliki S, Shields CL, Rojanaporn D, Al-Dahmash S, McLaughlin JP, Shields JA and Eagle RC Jr: High-risk retinoblastoma based on international classification of retinoblastoma: Analysis of 519 enucleated eyes. Ophthalmology. 120:997–1003. 2013. View Article : Google Scholar : PubMed/NCBI
12	Ha M and Kim VN: Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol. 15:509–524. 2014. View Article : Google Scholar : PubMed/NCBI
13	Kozomara A and Griffiths-Jones S: miRBase: Integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res. 39(Database Issue): D152–D157. 2011. View Article : Google Scholar : PubMed/NCBI
14	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
15	Baranwal S and Alahari SK: miRNA control of tumor cell invasion and metastasis. Int J Cancer. 126:1283–1290. 2010.PubMed/NCBI
16	Iorio MV and Croce CM: MicroRNA dysregulation in cancer: Diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Mol Med. 4:143–159. 2012. View Article : Google Scholar : PubMed/NCBI
17	Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 6:857–866. 2006. View Article : Google Scholar : PubMed/NCBI
18	Gao HY, Huo FC, Wang HY and Pei DS: MicroRNA-9 inhibits the gastric cancer cell proliferation by targeting TNFAIP8. Cell Prolif. 50:2017. View Article : Google Scholar
19	Li C, Lu S and Shi Y: MicroRNA-187 promotes growth and metastasis of gastric cancer by inhibiting FOXA2. Oncol Rep. 37:1747–1755. 2017. View Article : Google Scholar : PubMed/NCBI
20	Zeng Y, Zhu J, Shen D, Qin H, Lei Z, Li W, Liu Z and Huang JA: MicroRNA-205 targets SMAD4 in non-small cell lung cancer and promotes lung cancer cell growth in vitro and in vivo. Oncotarget. 8:30817–30829. 2017.PubMed/NCBI
21	Dong F, Xu T, Shen Y, Zhong S, Chen S, Ding Q and Shen Z: Dysregulation of miRNAs in bladder cancer: Altered expression with aberrant biogenesis procedure. Oncotarget. 8:27547–27568. 2017.PubMed/NCBI
22	Wang LL, Hu HF and Feng YQ: Suppressive effect of microRNA-143 in retinoblastoma. Int J Ophthalmol. 9:1584–1590. 2016.PubMed/NCBI
23	Hwang HW and Mendell JT: MicroRNAs in cell proliferation, cell death, and tumorigenesis. Br J Cancer. 96 Suppl:R40–R44. 2007.PubMed/NCBI
24	Han RL, Wang FP, Zhang PA, Zhou XY and Li Y: miR-383 inhibits ovarian cancer cell proliferation, invasion and aerobic glycolysis by targeting LDHA. Neoplasma. 64:244–252. 2017. View Article : Google Scholar : PubMed/NCBI
25	Li B, Xie Z, Li Z, Chen S and Li B: MicroRNA-613 targets FMNL2 and suppresses progression of colorectal cancer. Am J Transl Res. 8:5475–5484. 2016.PubMed/NCBI
26	Sun Z, Zhang A, Jiang T, Du Z, Che C and Wang F: MiR-145 suppressed human retinoblastoma cell proliferation and invasion by targeting ADAM19. Int J Clin Exp Pathol. 8:14521–14527. 2015.PubMed/NCBI
27	Montoya V, Fan H, Bryar PJ, Weinstein JL, Mets MB, Feng G, Martin J, Martin A, Jiang H and Laurie NA: Novel miRNA-31 and miRNA-200a-mediated regulation of retinoblastoma proliferation. PLoS One. 10:e01383662015. View Article : Google Scholar : PubMed/NCBI
28	Shen F, Mo MH, Chen L, An S, Tan X, Fu Y, Rezaei K, Wang Z, Zhang L and Fu SW: MicroRNA-21 down-regulates Rb1 expression by targeting PDCD4 in retinoblastoma. J Cancer. 5:804–812. 2014. View Article : Google Scholar : PubMed/NCBI
29	Chen T, Ren H, Thakur A, Yang T, Li Y, Zhang S, Wang T and Chen M: miR-382 inhibits tumor progression by targeting SETD8 in non-small cell lung cancer. Biomed Pharmacother. 86:248–253. 2017. View Article : Google Scholar : PubMed/NCBI
30	Zhou B, Song J, Han T, Huang M, Jiang H, Qiao H, Shi J and Wang Y: MiR-382 inhibits cell growth and invasion by targeting NR2F2 in colorectal cancer. Mol Carcinog. 55:2260–2267. 2016. View Article : Google Scholar : PubMed/NCBI
31	Ho JY, Hsu RJ, Liu JM, Chen SC, Liao GS, Gao HW and Yu CP: MicroRNA-382-5p aggravates breast cancer progression by regulating the RERG/Ras/ERK signaling axis. Oncotarget. 8:22443–22459. 2017.PubMed/NCBI
32	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
33	Stephan H, Zakrzewski JL, Bölöni R, Grasemann C, Lohmann DR and Eggert A: Neurotrophin receptor expression in human primary retinoblastomas and retinoblastoma cell lines. Pediatr Blood Cancer. 50:218–222. 2008. View Article : Google Scholar : PubMed/NCBI
34	Shang W, Yang Y, Zhang J and Wu Q: Long noncoding RNA BDNF-AS is a potential biomarker and regulates cancer development in human retinoblastoma. Biochem Biophys Res Commun. Jan 26–2017.(Epub ahead of print). View Article : Google Scholar
35	Mao XY, Zhou HH, Li X and Liu ZQ: Huperzine A alleviates oxidative glutamate toxicity in hippocampal HT22 cells via activating BDNF/TrkB-dependent PI3K/Akt/mTOR signaling pathway. Cell Mol Neurobiol. 36:915–925. 2016. View Article : Google Scholar : PubMed/NCBI
36	Xia H, Li Y and Lv X: MicroRNA-107 inhibits tumor growth and metastasis by targeting the BDNF-mediated PI3K/AKT pathway in human non-small lung cancer. Int J Oncol. 49:1325–1333. 2016.PubMed/NCBI
37	Huang Q, Liu L, Liu CH, You H, Shao F, Xie F, Lin XS, Hu SY and Zhang CH: MicroRNA-21 regulates the invasion and metastasis in cholangiocarcinoma and may be a potential biomarker for cancer prognosis. Asian Pac J Cancer Prev. 14:829–834. 2013. View Article : Google Scholar : PubMed/NCBI
38	Yu SH, Zhang CL, Dong FS and Zhang YM: miR-99a suppresses the metastasis of human non-small cell lung cancer cells by targeting AKT1 signaling pathway. J Cell Biochem. 116:268–276. 2015. View Article : Google Scholar : PubMed/NCBI
39	Funamizu N, Lacy CR, Parpart ST, Takai A, Hiyoshi Y and Yanaga K: MicroRNA-301b promotes cell invasiveness through targeting TP63 in pancreatic carcinoma cells. Int J Oncol. 44:725–734. 2014. View Article : Google Scholar : PubMed/NCBI
40	Wu X, Zeng Y, Wu S, Zhong J, Wang Y and Xu J: MiR-204, down-regulated in retinoblastoma, regulates proliferation and invasion of human retinoblastoma cells by targeting CyclinD2 and MMP-9. FEBS Lett. 589:645–650. 2015. View Article : Google Scholar : PubMed/NCBI
41	Wang J, Wang X, Wu G, Hou D and Hu Q: MiR-365b-3p, down-regulated in retinoblastoma, regulates cell cycle progression and apoptosis of human retinoblastoma cells by targeting PAX6. FEBS Lett. 587:1779–1786. 2013. View Article : Google Scholar : PubMed/NCBI
42	Xu M, Jin H, Xu CX, Sun B, Song ZG, Bi WZ and Wang Y: miR-382 inhibits osteosarcoma metastasis and relapse by targeting Y box-binding protein 1. Mol Ther. 23:89–98. 2015. View Article : Google Scholar : PubMed/NCBI
43	Qi B, Lu JG, Yao WJ, Chang TM, Qin XG, Ji YH, Wang TY, Liu SG, Li HC, Liu YZ and Zhao BS: Downregulation of microRNA-382 is associated with poor outcome of esophageal squamous cell carcinoma. World J Gastroenterol. 21:6884–6891. 2015. View Article : Google Scholar : PubMed/NCBI
44	Zhang W, Liu J, Qiu J, Fu X, Tang Q, Yang F, Zhao Z and Wang H: MicroRNA-382 inhibits prostate cancer cell proliferation and metastasis through targeting COUP-TFII. Oncol Rep. 36:3707–3715. 2016. View Article : Google Scholar : PubMed/NCBI
45	Tan H, He Q, Gong G, Wang Y, Li J, Wang J, Zhu D and Wu X: miR-382 inhibits migration and invasion by targeting ROR1 through regulating EMT in ovarian cancer. Int J Oncol. 48:181–190. 2016. View Article : Google Scholar : PubMed/NCBI
46	Xu M, Jin H, Xu CX, Sun B, Mao Z, Bi WZ and Wang Y: miR-382 inhibits tumor growth and enhance chemosensitivity in osteosarcoma. Oncotarget. 5:9472–9483. 2014. View Article : Google Scholar : PubMed/NCBI
47	Yu Z, Ni L, Chen D, Zhang Q, Su Z, Wang Y, Yu W, Wu X, Ye J, Yang S, et al: Identification of miR-7 as an oncogene in renal cell carcinoma. J Mol Histol. 44:669–677. 2013. View Article : Google Scholar : PubMed/NCBI
48	McAllister AK: Neurotrophins and neuronal differentiation in the central nervous system. Cell Mol Life Sci. 58:1054–1060. 2001. View Article : Google Scholar : PubMed/NCBI
49	Lai PC, Chiu TH and Huang YT: Overexpression of BDNF and TrkB in human bladder cancer specimens. Oncol Rep. 24:1265–1270. 2010.PubMed/NCBI
50	Choi B, Lee EJ, Shin MK, Park YS, Ryu MH, Kim SM, Kim EY, Lee HK and Chang EJ: Upregulation of brain-derived neurotrophic factor in advanced gastric cancer contributes to bone metastatic osteolysis by inducing long pentraxin 3. Oncotarget. 7:55506–55517. 2016. View Article : Google Scholar : PubMed/NCBI
51	Yang X, Martin TA and Jiang WG: Biological influence of brain-derived neurotrophic factor (BDNF) on colon cancer cells. Exp Ther Med. 6:1475–1481. 2013. View Article : Google Scholar : PubMed/NCBI
52	Yang X, Martin TA and Jiang WG: Biological influence of brain-derived neurotrophic factor on breast cancer cells. Int J Oncol. 41:1541–1546. 2012. View Article : Google Scholar : PubMed/NCBI
53	Huang SM, Lin C, Lin HY, Chiu CM, Fang CW, Liao KF, Chen DR and Yeh WL: Brain-derived neurotrophic factor regulates cell motility in human colon cancer. Endocr Relat Cancer. 22:455–464. 2015. View Article : Google Scholar : PubMed/NCBI
54	Zhang SY, Hui LP, Li CY, Gao J, Cui ZS and Qiu XS: More expression of BDNF associates with lung squamous cell carcinoma and is critical to the proliferation and invasion of lung cancer cells. BMC Cancer. 16:1712016. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

MicroRNA‑382 inhibits cell proliferation and invasion of retinoblastoma by targeting BDNF‑mediated PI3K/AKT signalling pathway

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