miR‑18a‑5p promotes cell invasion and migration of osteosarcoma by directly targeting IRF2

Lu,Chao; Peng,Kan; Guo,Hao; Ren,Xiaoyu; Hu,Shouye; Cai,Yuanzhen; Han,Yan; Ma,Le; Xu,Peng

doi:10.3892/ol.2018.9032

miR‑18a‑5p promotes cell invasion and migration of osteosarcoma by directly targeting IRF2

Authors:
- Chao Lu
- Kan Peng
- Hao Guo
- Xiaoyu Ren
- Shouye Hu
- Yuanzhen Cai
- Yan Han
- Le Ma
- Peng Xu
View Affiliations

Affiliations: Department of Joint Surgery, Xi'an Honghui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710054, P.R. China, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China
Published online on: June 27, 2018 https://doi.org/10.3892/ol.2018.9032
Pages: 3150-3156

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

An increasing number of studies have suggested that microRNAs (miRNAs) are involved in the progress of many human cancers including osteosarcoma (OS). Especially, microRNA‑18a‑5p (miR‑18a‑5p) has been reported to associate with the occurrence, development and clinical outcomes of human cancers. Therefore, we investigated the functions of miR‑18a‑5p in OS. Reverse transcription‑quantitative PCR (RT‑qPCR) showed that miR‑18a‑5p was significantly upregulated in OS tissues and cell lines (MG‑63 and Saos‑2). The overexpression of miR‑18a‑5p was found to significantly promote cell migration and invasion in MG‑63 cells via Transwell assay. Moreover, luciferase reporter assays indicated that interferon regulatory factor (IRF)2 was a direct target of miR‑18a‑5p. IRF2 was downregulated in MG‑63 and Saos‑2 cell lines. Furthermore, Transwell analysis showed that the knockout of IRF2 promoted cell migration and invasion in MG‑63 cells. Carcinogenesis of miR‑18a‑5p was reversed by the overexpression of IRF2 in OS. In conclusion, miR‑18a‑5p promoted the invasion and migration of OS cells through inhibiting IRF2 expression. Thus, miR‑18a‑5p might act as a potential target for the diagnosis and treatment of OS in the future.

View Figures

View References

1	Poletajew S, Fus L and Wasiutyński A: Current concepts on pathogenesis and biology of metastatic osteosarcoma tumors. Ortop Traumatol Rehabil. 13:537–545. 2011. View Article : Google Scholar : PubMed/NCBI
2	Lewis VO: What's new in musculoskeletal oncology. J Bone Joint Surg Am. 89:1399–1407. 2007. View Article : Google Scholar : PubMed/NCBI
3	Fujiwara T, Katsuda T, Hagiwara K, Kosaka N, Yoshioka Y, Takahashi RU, Takeshita F, Kubota D, Kondo T, Ichikawa H, et al: Clinical relevance and therapeutic significance of microRNA-133a expression profiles and functions in malignant osteosarcoma-initiating cells. Stem Cells. 32:959–973. 2014. View Article : Google Scholar : PubMed/NCBI
4	Debebe Z and Rathmell WK: Ror2 as a therapeutic target in cancer. Pharmacol Ther. 150:143–148. 2015. View Article : Google Scholar : PubMed/NCBI
5	Geng S, Zhang X, Chen J, Liu X, Zhang H, Xu X, Ma Y, Li B, Zhang Y, Bi Z, et al: The tumor suppressor role of miR-124 in osteosarcoma. PLoS One. 9:e915662014. View Article : Google Scholar : PubMed/NCBI
6	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
7	Li X, Luo F, Li Q, Xu M, Feng D, Zhang G and Wu W: Identification of new aberrantly expressed miRNAs in intestinal-type gastric cancer and its clinical significance. Oncol Rep. 26:1431–1439. 2011.PubMed/NCBI
8	Luo Z, Dai Y, Zhang L, Jiang C, Li Z, Yang J, McCarthy JB, She X, Zhang W, Ma J, et al: miR-18a promotes malignant progression by impairing microRNA biogenesis in nasopharyngeal carcinoma. Carcinogenesis. 34:415–425. 2013. View Article : Google Scholar : PubMed/NCBI
9	Wu CW, Dong YJ, Liang QY, He XQ, Ng SS, Chan FK, Sung JJ and Yu J: MicroRNA-18a attenuates DNA damage repair through suppressing the expression of ataxia telangiectasia mutated in colorectal cancer. PLoS One. 8:e570362013. View Article : Google Scholar : PubMed/NCBI
10	Song Y, Wang P, Zhao W, Yao Y, Liu X, Ma J, Xue Y and Liu Y: MiR-18a regulates the proliferation, migration and invasion of human glioblastoma cell by targeting neogenin. Exp Cell Res. 324:54–64. 2014. View Article : Google Scholar : PubMed/NCBI
11	Tao J, Wu D, Li P, Xu B, Lu Q and Zhang W: microRNA-18a, a member of the oncogenic miR-17-92 cluster, targets Dicer and suppresses cell proliferation in bladder cancer T24 cells. Mol Med Rep. 5:167–172. 2012.PubMed/NCBI
12	Yanai H, Negishi H and Taniguchi T: The IRF family of transcription factors: Inception, impact and implications in oncogenesis. Oncoimmunology. 1:1376–1386. 2012. View Article : Google Scholar : PubMed/NCBI
13	Chen YJ, Wu H, Zhu JM, Li XD, Luo SW, Dong L, Liu TT and Shen XZ: MicroRNA-18a modulates P53 expression by targeting IRF2 in gastric cancer patients. J Gastroenterol Hepatol. 31:155–163. 2016. View Article : Google Scholar : PubMed/NCBI
14	Sakai T, Mashima H, Yamada Y, Goto T, Sato W, Dohmen T, Kamada K, Yoshioka M, Uchinami H, Yamamoto Y, et al: The roles of interferon regulatory factors 1 and 2 in the progression of human pancreatic cancer. Pancreas. 43:909–916. 2014. View Article : Google Scholar : PubMed/NCBI
15	Nicolini A, Carpi A and Rossi G: Cytokines in breast cancer. Cytokine Growth Factor Rev. 17:325–337. 2006. View Article : Google Scholar : PubMed/NCBI
16	Dorand RD, Nthale J, Myers JT, Barkauskas DS, Avril S, Chirieleison SM, Pareek TK, Abbott DW, Stearns DS, Letterio JJ, et al: Cdk5 disruption attenuates tumor PD-L1 expression and promotes antitumor immunity. Science. 353:399–403. 2016. View Article : Google Scholar : PubMed/NCBI
17	Amaddeo G, Guichard C, Imbeaud S and Zucman-Rossi J: Next-generation sequencing identified new oncogenes and tumor suppressor genes in human hepatic tumors. Oncoimmunology. 1:1612–1613. 2012. View Article : Google Scholar : PubMed/NCBI
18	Xi H and Blanck G: Interferon regulatory factor-2 point mutations in human pancreatic tumors. Int J Cancer. 87:803–808. 2000. 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	Hayashita Y, Osada H, Tatematsu Y, Yamada H, Yanagisawa K, Tomida S, Yatabe Y, Kawahara K, Sekido Y and Takahashi T: A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res. 65:9628–9632. 2005. View Article : Google Scholar : PubMed/NCBI
21	Takakura S, Mitsutake N, Nakashima M, Namba H, Saenko VA, Rogounovitch TI, Nakazawa Y, Hayashi T, Ohtsuru A and Yamashita S: Oncogenic role of miR-17-92 cluster in anaplastic thyroid cancer cells. Cancer Sci. 99:1147–1154. 2008. View Article : Google Scholar : PubMed/NCBI
22	Diosdado B, van de Wiel MA, Terhaar Sive Droste JS, Mongera S, Postma C, Meijerink WJ, Carvalho B and Meijer GA: MiR-17-92 cluster is associated with 13q gain and c-myc expression during colorectal adenoma to adenocarcinoma progression. Br J Cancer. 101:707–714. 2009. View Article : Google Scholar : PubMed/NCBI
23	Chow TF, Mankaruos M, Scorilas A, Youssef Y, Girgis A, Mossad S, Metias S, Rofael Y, Honey RJ, Stewart R, et al: The miR-17-92 cluster is overexpressed in and has an oncogenic effect on renal cell carcinoma. J Urol. 183:743–751. 2010. View Article : Google Scholar : PubMed/NCBI
24	van Haaften G and Agami R: Tumorigenicity of the miR-17-92 cluster distilled. Genes Dev. 24:1–4. 2010. View Article : Google Scholar : PubMed/NCBI
25	Sarkar S, Balasuriya UB, Horohov DW and Chambers TM: Equine herpesvirus-1 infection disrupts interferon regulatory factor-3 (IRF-3) signaling pathways in equine endothelial cells. Vet Immunol Immunopathol. 173:1–9. 2016. View Article : Google Scholar : PubMed/NCBI
26	Liu F, Yu X, Huang H, Chen X, Wang J, Zhang X and Lin Q: Upregulation of microRNA-450 inhibits the progression of lung cancer in vitro and in vivo by targeting interferon regulatory factor 2. Int J Mol Med. 38:283–290. 2016. View Article : Google Scholar : PubMed/NCBI
27	Liang C, Zhang X, Wang HM, Liu XM, Zhang XJ, Zheng B, Qian GR and Ma ZL: MicroRNA-18a-5p functions as an oncogene by directly targeting IRF2 in lung cancer. Cell Death Dis. 8:e27642017. View Article : Google Scholar : PubMed/NCBI
28	He Y and Yu B: MicroRNA-93 promotes cell proliferation by directly targeting P21 in osteosarcoma cells. Exp Ther Med. 13:2003–2011. 2017. View Article : Google Scholar : PubMed/NCBI
29	Jiang R, Zhang C, Liu G, Gu R and Wu H: MicroRNA-126 inhibits proliferation, migration, invasion and EMT in osteosarcoma by targeting ZEB1. J Cell Biochem. 118:3765–3774. 2017. View Article : Google Scholar : PubMed/NCBI
30	Lin W, Zhu X, Yang S, Chen X, Wang L, Huang Z, Ding Y, Huang L and Lv C: MicroRNA-203 inhibits proliferation and invasion, and promotes apoptosis of osteosarcoma cells by targeting Runt-related transcription factor 2. Biomed Pharmacother. 91:1075–1084. 2017. View Article : Google Scholar : PubMed/NCBI
31	Mamane Y, Heylbroeck C, Génin P, Algarté M, Servant MJ, LePage C, DeLuca C, Kwon H, Lin R and Hiscott J: Interferon regulatory factors: The next generation. Gene. 237:1–14. 1999. View Article : Google Scholar : PubMed/NCBI
32	Harada H, Fujita T, Miyamoto M, Kimura Y, Maruyama M, Furia A, Miyata T and Taniguchi T: Structurally similar but functionally distinct factors, IRF-1 and IRF-2, bind to the same regulatory elements of IFN and IFN-inducible genes. Cell. 58:729–739. 1989. View Article : Google Scholar : PubMed/NCBI
33	Choo A, Palladinetti P, Holmes T, Basu S, Shen S, Lock RB, O'Brien TA, Symonds G and Dolnikov A: siRNA targeting the IRF2 transcription factor inhibits leukaemic cell growth. Int J Oncol. 33:175–183. 2008.PubMed/NCBI