MicroRNA‑584 prohibits hepatocellular carcinoma cell proliferation and invasion by directly targeting BDNF Retraction in /10.3892/mmr.2024.13248

Song,Yanan; Wang,Guoyu; Zhuang,Juhua; Ni,Jing; Zhang,Suiliang; Ye,Ying; Xia,Wei

doi:10.3892/mmr.2019.10424

MicroRNA‑584 prohibits hepatocellular carcinoma cell proliferation and invasion by directly targeting BDNF

Retraction in: /10.3892/mmr.2024.13248

Authors:
- Yanan Song
- Guoyu Wang
- Juhua Zhuang
- Jing Ni
- Suiliang Zhang
- Ying Ye
- Wei Xia
View Affiliations

Affiliations: Department of Nuclear Medicine, The Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200137, P.R. China, Department of Oncology, The Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200137, P.R. China
Published online on: June 25, 2019 https://doi.org/10.3892/mmr.2019.10424
Pages: 1994-2001

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

In recent decades, an increasing number of studies have demonstrated that numerous microRNAs (miRNAs) are dysregulated in hepatocellular carcinoma (HCC); these aberrantly expressed miRNAs are contributing regulators of HCC formation and progression. Thus, revealing the biological roles of miRNAs in HCC may provide novel information on the identification of effective therapeutic targets and valuable diagnosis methods. Herein, reverse transcription‑quantitative PCR was performed to determine the expression profile of miRNA‑584 (miR‑584) in HCC tissues and cell lines. Cell Counting Kit‑8 and cell invasion assays were utilized to evaluate the influence of mIR‑584 overexpression on HCC cell proliferation and invasion, respectively. The present study demonstrated that miR‑584 expression was reduced in HCC tissues and cell lines compared with normal controls. Clinical analysis indicated that decreased miR‑584 expression was significantly associated with tumor size, TNM stage and lymph node metastasis of patients with HCC. Additionally, resumption of miR‑584 expression inhibited proliferation and invasion of HCC cells. Mechanistically, it was demonstrated that miR‑584 can directly interact with the 3'‑untranslated regions of brain‑derived neurotrophic factor (BDNF) mRNA, and reduce its mRNA and protein levels in HCC cells. Furthermore, BDNF was upregulated in HCC tissues, and its level was inversely correlated with miR‑584 expression. Notably, restored BDNF expression antagonized the inhibitory effects of miR‑584 overexpression on HCC cells. In conclusion, miR‑584 may serve tumor‑suppressive roles in HCC by directly targeting BDNF, thus suggesting that miR‑584 may serve as a potential candidate for treatment of patients with this disease.

View Figures

View References

1	Forner A, Llovet JM and Bruix J: Hepatocellular carcinoma. Lancet. 379:1245–1255. 2012. View Article : Google Scholar : PubMed/NCBI
2	Ferlay J, Parkin DM and Steliarova-Foucher E: Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer. 46:765–781. 2010. View Article : Google Scholar : PubMed/NCBI
3	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
4	Kakar S, Grenert JP, Paradis V, Pote N, Jakate S and Ferrell LD: Hepatocellular carcinoma arising in adenoma: Similar immunohistochemical and cytogenetic features in adenoma and hepatocellular carcinoma portions of the tumor. Mod Pathol. 27:1499–1509. 2014. View Article : Google Scholar : PubMed/NCBI
5	Mlynarsky L, Menachem Y and Shibolet O: Treatment of hepatocellular carcinoma: Steps forward but still a long way to go. World J Hepatol. 7:566–574. 2015. View Article : Google Scholar : PubMed/NCBI
6	El-Serag HB and Rudolph KL: Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis. Gastroenterology. 132:2557–2576. 2007. View Article : Google Scholar : PubMed/NCBI
7	Bialecki ES and Di Bisceglie AM: Diagnosis of hepatocellular carcinoma. HPB (Oxford). 7:26–34. 2005. View Article : Google Scholar : PubMed/NCBI
8	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
9	Jonas S and Izaurralde E: Towards a molecular understanding of microRNA-mediated gene silencing. Nat Rev Genet. 16:421–433. 2015. View Article : Google Scholar : PubMed/NCBI
10	Yates LA, Norbury CJ and Gilbert RJ: The long and short of microRNA. Cell. 153:516–519. 2013. View Article : Google Scholar : PubMed/NCBI
11	Huang XH, Wang Q, Chen JS, Fu XH, Chen XL, Chen LZ, Li W, Bi J, Zhang LJ, Fu Q, et al: Bead-based microarray analysis of microRNA expression in hepatocellular carcinoma: MiR-338 is downregulated. Hepatol Res. 39:786–794. 2009. View Article : Google Scholar : PubMed/NCBI
12	Shih TC, Tien YJ, Wen CJ, Yeh TS, Yu MC, Huang CH, Lee YS, Yen TC and Hsieh SY: MicroRNA-214 downregulation contributes to tumor angiogenesis by inducing secretion of the hepatoma-derived growth factor in human hepatoma. J Hepatol. 57:584–591. 2012. View Article : Google Scholar : PubMed/NCBI
13	Yang P, Li QJ, Feng Y, Zhang Y, Markowitz GJ, Ning S, Deng Y, Zhao J, Jiang S, Yuan Y, et al: TGF-β-miR-34a-CCL22 signaling-induced Treg cell recruitment promotes venous metastases of HBV-positive hepatocellular carcinoma. Cancer Cell. 22:291–303. 2012. View Article : Google Scholar : PubMed/NCBI
14	Zhou K, Luo X, Wang Y, Cao D and Sun G: MicroRNA-30a suppresses tumor progression by blocking Ras/Raf/MEK/ERK signaling pathway in hepatocellular carcinoma. Biomed Pharmacother. 93:1025–1032. 2017. View Article : Google Scholar : PubMed/NCBI
15	Xu Q, Liu X, Liu Z, Zhou Z, Wang Y, Tu J, Li L, Bao H, Yang L and Tu K: MicroRNA-1296 inhibits metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by targeting SRPK1-mediated PI3K/AKT pathway. Mol Cancer. 16:1032017. View Article : Google Scholar : PubMed/NCBI
16	Xu Y, Ge K, Lu J, Huang J, Wei W and Huang Q: MicroRNA-493 suppresses hepatocellular carcinoma tumorigenesis through down-regulation of anthrax toxin receptor 1 (ANTXR1) and R-Spondin 2 (RSPO2). Biomed Pharmacother. 93:334–343. 2017. View Article : Google Scholar : PubMed/NCBI
17	Luo X, Yang S, Zhou C, Pan F, Li Q and Ma S: MicroRNA-328 enhances cellular motility through posttranscriptional regulation of PTPRJ in human hepatocellular carcinoma. Onco Targets Ther. 8:3159–3167. 2015.PubMed/NCBI
18	Yu L, Gong X, Sun L, Yao H, Lu B and Zhu L: miR-454 functions as an oncogene by inhibiting CHD5 in hepatocellular carcinoma. Oncotarget. 6:39225–39234. 2015. View Article : Google Scholar : PubMed/NCBI
19	Xue H, Guo X, Han X, Yan S, Zhang J, Xu S, Li T, Guo X, Zhang P, Gao X, et al: MicroRNA-584-3p, a novel tumor suppressor and prognostic marker, reduces the migration and invasion of human glioma cells by targeting hypoxia-induced ROCK1. Oncotarget. 7:4785–4805. 2016. View Article : Google Scholar : PubMed/NCBI
20	Xiang X, Mei H, Qu H, Zhao X, Li D, Song H, Jiao W, Pu J, Huang K, Zheng L and Tong Q: miRNA-584-5p exerts tumor suppressive functions in human neuroblastoma through repressing transcription of matrix metalloproteinase 14. Biochim Biophys Acta. 1852:1743–1754. 2015. View Article : Google Scholar : PubMed/NCBI
21	Zheng L, Chen Y, Ye L, Jiao W, Song H, Mei H, Li D, Yang F, Li H, Huang K and Tong Q: miRNA-584-3p inhibits gastric cancer progression by repressing Yin Yang 1-facilitated MMP-14 expression. Sci Rep. 7:89672017. View Article : Google Scholar : PubMed/NCBI
22	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
23	Yang ZF, Ho DW, Lam CT, Luk JM, Lum CT, Yu WC, Poon RT and Fan ST: Identification of brain-derived neurotrophic factor as a novel functional protein in hepatocellular carcinoma. Cancer Res. 65:219–225. 2005.PubMed/NCBI
24	Guo D, Sun W, Zhu L, Zhang H, Hou X, Liang J, Jiang X and Liu C: Knockdown of BDNF suppressed invasion of HepG2 and HCCLM3 cells, a mechanism associated with inactivation of RhoA or Rac1 and actin skeleton disorganization. APMIS. 120:469–476. 2012. View Article : Google Scholar : PubMed/NCBI
25	Zhang L, Tu Y, He W, Peng Y and Qiu Z: A novel mechanism of hepatocellular carcinoma cell apoptosis induced by lupeol via Brain-Derived Neurotrophic Factor Inhibition and Glycogen Synthase Kinase 3 beta reactivation. Eur J Pharmacol. 762:55–62. 2015. View Article : Google Scholar : PubMed/NCBI
26	Long J, Jiang C, Liu B, Fang S and Kuang M: MicroRNA-15a-5p suppresses cancer proliferation and division in human hepatocellular carcinoma by targeting BDNF. Tumour Biol. 37:5821–5828. 2016. View Article : Google Scholar : PubMed/NCBI
27	Hayes CN and Chayama K: MicroRNAs as biomarkers for liver disease and hepatocellular carcinoma. Int J Mol Sci. 17:2802016. View Article : Google Scholar : PubMed/NCBI
28	Fiorino S, Bacchi-Reggiani ML, Visani M, Acquaviva G, Fornelli A, Masetti M, Tura A, Grizzi F, Zanello M, Mastrangelo L, et al: MicroRNAs as possible biomarkers for diagnosis and prognosis of hepatitis B- and C-related-hepatocellular-carcinoma. World J Gastroenterol. 22:3907–3936. 2016. View Article : Google Scholar : PubMed/NCBI
29	Mao B and Wang G: MicroRNAs involved with hepatocellular carcinoma (Review). Oncol Rep. 34:2811–2820. 2015. View Article : Google Scholar : PubMed/NCBI
30	Wang XP, Deng XL and Li LY: MicroRNA-584 functions as a tumor suppressor and targets PTTG1IP in glioma. Int J Clin Exp Pathol. 7:8573–8582. 2014.PubMed/NCBI
31	Ueno K, Hirata H, Shahryari V, Chen Y, Zaman MS, Singh K, Tabatabai ZL, Hinoda Y and Dahiya R: Tumour suppressor microRNA-584 directly targets oncogene Rock-1 and decreases invasion ability in human clear cell renal cell carcinoma. Br J Cancer. 104:308–315. 2011. View Article : Google Scholar : PubMed/NCBI
32	Xiang J, Wu Y, Li DS, Wang ZY, Shen Q, Sun TQ, Guan Q and Wang YJ: miR-584 suppresses invasion and cell migration of thyroid carcinoma by regulating the target oncogene ROCK1. Oncol Res Treat. 38:436–440. 2015. View Article : Google Scholar : PubMed/NCBI
33	Xu S, Zhang J, Xue H, Guo X, Han X, Li T, Guo X, Gao X, Liu Q and Li G: MicroRNA-584-3p reduces the vasculogenic mimicry of human glioma cells by regulating hypoxia-induced ROCK1 dependent stress fiber formation. Neoplasma. 64:13–21. 2017. View Article : Google Scholar : PubMed/NCBI
34	Li Q, Li Z, Wei S, Wang W, Chen Z, Zhang L, Chen L, Li B, Sun G, Xu J, et al: Overexpression of miR-584-5p inhibits proliferation and induces apoptosis by targeting WW domain-containing E3 ubiquitin protein ligase 1 in gastric cancer. J Exp Clin Cancer Res. 36:592017. View Article : Google Scholar : PubMed/NCBI
35	Orlandella FM, Di Maro G, Ugolini C, Basolo F and Salvatore G: TWIST1/miR-584/TUSC2 pathway induces resistance to apoptosis in thyroid cancer cells. Oncotarget. 7:70575–70588. 2016. View Article : Google Scholar : PubMed/NCBI
36	Schickel R, Boyerinas B, Park SM and Peter ME: MicroRNAs: Key players in the immune system, differentiation, tumorigenesis and cell death. Oncogene. 27:5959–5974. 2008. View Article : Google Scholar : PubMed/NCBI
37	Barde YA, Edgar D and Thoenen H: Purification of a new neurotrophic factor from mammalian brain. EMBO J. 1:549–553. 1982. View Article : Google Scholar : PubMed/NCBI
38	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
39	Au CW, Siu MK, Liao X, Wong ES, Ngan HY, Tam KF, Chan DC, Chan QK and Cheung AN: Tyrosine kinase B receptor and BDNF expression in ovarian cancers-Effect on cell migration, angiogenesis and clinical outcome. Cancer Lett. 281:151–161. 2009. View Article : Google Scholar : PubMed/NCBI
40	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
41	Radin DP and Patel P: BDNF: An oncogene or tumor suppressor? Anticancer Res. 37:3983–3990. 2017.PubMed/NCBI
42	Tayyab M, Shahi MH, Farheen S, Mariyath MPM, Khanam N, Castresana JS and Hossain MM: Sonic hedgehog, Wnt, and brain-derived neurotrophic factor cell signaling pathway crosstalk: Potential therapy for depression. J Neurosci Res. 96:53–62. 2018. View Article : Google Scholar : PubMed/NCBI
43	Tajbakhsh A, Mokhtari-Zaer A, Rezaee M, Afzaljavan F, Rivandi M, Hassanian SM, Ferns GA, Pasdar A and Avan A: Therapeutic potentials of BDNF/TrkB in breast cancer; Current status and perspectives. J Cell Biochem. 118:2502–2515. 2017. View Article : Google Scholar : PubMed/NCBI