MicroRNA-181a promotes proliferation and inhibits apoptosis by suppressing CFIm25 in osteosarcoma

Zhu,Zhong‑Jiao; Huang,Peng; Chong,Yan‑Xue; Kang,Li‑Xin; Huang,Xing; Zhu,Zhong‑Xiu; Nie,Lin

doi:10.3892/mmr.2016.5741

MicroRNA-181a promotes proliferation and inhibits apoptosis by suppressing CFIm25 in osteosarcoma

Authors:
- Zhong‑Jiao Zhu
- Peng Huang
- Yan‑Xue Chong
- Li‑Xin Kang
- Xing Huang
- Zhong‑Xiu Zhu
- Lin Nie
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Affiliations: Department of Orthopedics, Tengzhou Central People's Hospital, Tengzhou, Shandong 277500, P.R. China, Department of Emergency, Tengzhou Hospital of Traditional Chinese Medicine, Tengzhou, Shandong 277500, P.R. China, Department of Pharmacy Intravenous Admixture Service, Tengzhou Central People's Hospital, Tengzhou, Shandong 277500, P.R. China, Department of Oncology, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, Shandong 250031, P.R. China, Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
Published online on: September 14, 2016 https://doi.org/10.3892/mmr.2016.5741
Pages: 4271-4278

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Abstract

MicroRNA-181a (miR-181a) is upregulated in osteosarcoma, and its overexpression promotes the proliferation and inhibits the apoptosis of osteosarcoma cells. However, the mechanism of miR‑181a as an oncogene remains to be fully elucidated in osteosarcoma. Cleavage factor (CF) Im25 links alternative polyadenylation to glioblastoma tumor suppression, however, its role in osteosarcoma has not been reported. In the present study, it was confirmed that the expression of miR‑181a was upregulated in osteosarcoma, and that silencing miR‑181a inhibited the proliferation and promoted the apoptosis of osteosarcoma cells. miRNAs are short non‑coding RNAs, which regulate target mRNAs by binding predominantly to the 3'untranslated region (3'UTR), inducing either translational repression or degradation of the target. In the present study, target genes of miR‑181a were screened using miRanda, which is a commonly used prediction algorithm. It was found that miR‑181a targeted the 3'UTR of CFIm25 mRNA. Subsequent experiments confirmed that miR‑181a downregulated the expression of CFIm25 in osteosarcoma cells. Finally, it was demonstrated that the CFIm25 protein was also downregulated in osteosarcoma tissues, and inhibited the proliferation and promoted the apoptosis of the cells. Elucidating the roles of miR‑181a and CFIm25 in osteosarcoma not only assists in further understanding the pathogenesis and progression of this disease, but also offers novel targets for effective therapies.

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1	Sweetnam R: Osteosarcoma. Br J Hosp Med. 28(112): 116–121. 1982.
2	Mirabello L, Troisi RJ and Savage SA: Osteosarcoma incidence and survival rates from 1973 to 2004: Data from the surveillance, epidemiology, and end results program. Cancer. 115:1531–1543. 2009. View Article : Google Scholar : PubMed/NCBI
3	Ottaviani G and Jaffe N: The epidemiology of osteosarcoma. Cancer Treat Res. 152:3–13. 2009. View Article : Google Scholar : PubMed/NCBI
4	Damron TA, Ward WG and Stewart A: Osteosarcoma, chondrosarcoma, and Ewing's sarcoma. National Cancer Data Base report. Clin Orthop Relat Res. 459:40–47. 2007. View Article : Google Scholar : PubMed/NCBI
5	Dorfman HD and Czerniak B: Bone cancers. Cancer. 75:(1 Suppl). S203–S210. 1995. View Article : Google Scholar
6	Geller DS and Gorlick R: Osteosarcoma: A review of diagnosis, management, and treatment strategies. Clin Adv Hematol Oncol. 8:705–718. 2010.PubMed/NCBI
7	Bielack SS, Marina N, Ferrari S, Helman LJ, Smeland S, Whelan JS and Reaman GH: Osteosarcoma: The same old drugs or more? J Clin Oncol. 26:3102–3103; author reply 3104–3105. 2008. View Article : Google Scholar : PubMed/NCBI
8	Chou AJ, Geller DS and Gorlick R: Therapy for osteosarcoma: Where do we go from here? Paediatr Drugs. 10:315–327. 2008. View Article : Google Scholar : PubMed/NCBI
9	O'Day K and Gorlick R: Novel therapeutic agents for osteosarcoma. Expert Rev Anticancer Ther. 9:511–523. 2009. View Article : Google Scholar : PubMed/NCBI
10	Bernthal NM, Federman N, Eilber FR, Nelson SD, Eckardt JJ, Eilber FC and Tap WD: Long-term results (>25 years) of a randomized, prospective clinical trial evaluating chemotherapy in patients with high-grade, operable osteosarcoma. Cancer. 118:5888–5893. 2012. View Article : Google Scholar : PubMed/NCBI
11	Link MP, Goorin AM, Miser AW, Green AA, Pratt CB, Belasco JB, Pritchard J, Malpas JS, Baker AR, Kirkpatrick JA, et al: The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity. N Engl J Med. 314:1600–1606. 1986. View Article : Google Scholar : PubMed/NCBI
12	Sandberg R, Neilson JR, Sarma A, Sharp PA and Burge CB: Proliferating cells express mRNAs withshortened 3′ untranslated regions and fewer microRNA target sites. Science. 320:1643–1647. 2008. View Article : Google Scholar : PubMed/NCBI
13	Mayr C and Bartel DP: Widespread shortening of 3′UTRs by alternative cleavage and polyadenylation activates oncogenes in cancer cells. Cell. 138:673–684. 2009. View Article : Google Scholar : PubMed/NCBI
14	Ji Z, Lee JY, Pan Z, Jiang B and Tian B: Progressive lengthening of 3′ untranslated regions of mRNAs by alternative polyadenylation during mouse embryonic development. Proc Natl Acad Sci USA. 106:7028–7033. 2009. View Article : Google Scholar : PubMed/NCBI
15	Mangone M, Manoharan AP, Thierry-Mieg D, Thierry-Mieg J, Han T, Mackowiak SD, Mis E, Zegar C, Gutwein MR, Khivansara V, et al: The landscape of C. elegans 3′UTRs. Science. 329:432–435. 2010. View Article : Google Scholar : PubMed/NCBI
16	Jacobson A and Peltz SW: Interrelationships of the pathways of mRNA decay and translation in eukaryotic cells. Annu Rev Biochem. 65:693–739. 1996. View Article : Google Scholar : PubMed/NCBI
17	Wickens M, Anderson P and Jackson RJ: Life and death in the cytoplasm: Messages from the 3′ end. Curr Opin Genet Dev. 7:220–232. 1997. View Article : Google Scholar : PubMed/NCBI
18	Garneau NL, Wilusz J and Wilusz CJ: The highways and byways of mRNA decay. Nat Rev Mol Cell Biol. 8:113–126. 2007. View Article : Google Scholar : PubMed/NCBI
19	McCracken S, Fong N, Rosonina E, Yankulov K, Brothers G, Siderovski D, Hessel A, Foster S, Shuman S and Bentley DL: 5′-Capping enzymes are targeted to pre-mRNA by binding to the phosphorylated carboxy-terminal domain of RNA polymerase II. Genes Dev. 11:3306–3318. 1997. View Article : Google Scholar : PubMed/NCBI
20	Hirose Y and Manley JL: RNA polymerase II is an essential mRNA polyadenylation factor. Nature. 395:93–96. 1998. View Article : Google Scholar : PubMed/NCBI
21	Shi Y, Di Giammartino DC, Taylor D, Sarkeshik A, Rice WJ, Yates JR III, Frank J and Manley JL: Molecular architecture of the human pre-mRNA 3′ processing complex. Mol Cell. 33:365–376. 2009. View Article : Google Scholar : PubMed/NCBI
22	Masamha CP, Xia Z, Yang J, Albrecht TR, Li M, Shyu AB, Li W and Wagner EJ: CFIm25 links alternative polyadenylation to glioblastoma tumour suppression. Nature. 510:412–416. 2014.PubMed/NCBI
23	Elkon R, Drost J, van Haaften G, Jenal M, Schrier M, Vrielink JA Oude and Agami R: E2F mediates enhanced alternative polyadenylation in proliferation. Genome Biol. 13:R592012. View Article : Google Scholar : PubMed/NCBI
24	Lee RC, Feinbaum RL and Ambros V: The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 75:843–854. 1993. View Article : Google Scholar : PubMed/NCBI
25	Pasquinelli AE, Reinhart BJ, Slack F, Martindale MQ, Kuroda MI, Maller B, Hayward DC, Ball EE, Degnan B, Müller P, et al: Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature. 408:86–89. 2000. View Article : Google Scholar : PubMed/NCBI
26	Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, Horvitz HR and Ruvkun G: The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature. 403:901–906. 2000. View Article : Google Scholar : PubMed/NCBI
27	Kobayashi E, Satow R, Ono M, Masuda M, Honda K, Sakuma T, Kawai A, Morioka H, Toyama Y and Yamada T: MicroRNA expression and functional profiles of osteosarcoma. Oncology. 86:94–103. 2014. View Article : Google Scholar : PubMed/NCBI
28	Osaki M, Takeshita F, Sugimoto Y, Kosaka N, Yamamoto Y, Yoshioka Y, Kobayashi E, Yamada T, Kawai A, Inoue T, et al: MicroRNA-143 regulates human osteosarcoma metastasis by regulating matrix metalloprotease-13 expression. Mol Ther. 19:1123–1130. 2011. View Article : Google Scholar : PubMed/NCBI
29	Duan Z, Choy E, Harmon D, Liu X, Susa M, Mankin H and Hornicek F: MicroRNA-199a-3p is downregulated in human osteosarcoma and regulates cell proliferation and migration. Mol Cancer Ther. 10:1337–1345. 2011. View Article : Google Scholar : PubMed/NCBI
30	Kloosterman WP and Plasterk RH: The diverse functions of microRNAs in animal development and disease. Dev Cell. 11:441–450. 2006. View Article : Google Scholar : PubMed/NCBI
31	Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST and Patel T: MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 133:647–658. 2007. View Article : Google Scholar : PubMed/NCBI
32	Jovanovic M and Hengartner MO: miRNAs and apoptosis: RNAs to die for. Oncogene. 25:6176–6187. 2006. View Article : Google Scholar : PubMed/NCBI
33	Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, et al: MicroRNA expression profiles classify human cancers. Nature. 435:834–838. 2005. View Article : Google Scholar : PubMed/NCBI
34	Esquela-Kerscher A and Slack FJ: Oncomirs-microRNAs with a role in cancer. Nat Rev Cancer. 6:259–269. 2006. View Article : Google Scholar : PubMed/NCBI
35	Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 6:857–866. 2006. View Article : Google Scholar : PubMed/NCBI
36	Deng G, Hu C, Zhu L, Huang F, Huang W, Xu H and Nie W: Downregulation of ROS-FIG inhibits cell proliferation, colony-formation, cell cycle progression, migration and invasion, while inducing apoptosis in intrahepatic cholangiocarcinoma cells. Int J Mol Med. 34:661–668. 2014.PubMed/NCBI
37	Zhang ZG, Niu XY, He XJ and Shu J: Ginsenoside Rg1 reduces toxicity of fine particulate matter on human alveolar epithelial cells: A preliminary observation. Mol Med Rep. 9:989–992. 2014.PubMed/NCBI
38	Tsujimoto M, Doi T, Kuroyanagi G, Yamamoto N, Matsushima-Nishiwaki R, Iida Y, Enomoto Y, Iida H, Ogura S, Otsuka T, et al: αB-crystallin reduces ristocetin-induced soluble CD40 ligand release in human platelets: Suppression of thromboxane A2 generation. Mol Med Rep. 12:357–362. 2015.PubMed/NCBI
39	Zhang F, Li ZL, Xu XM, Hu Y, Yao JH, Xu W, Jing HR, Wang S, Ning SL and Tian XF: Protective effects of icariin-mediated SIRT1/FOXO3 signaling pathway on intestinal ischemia/reperfusion-induced acute lung injury. Mol Med Rep. 11:269–276. 2015.PubMed/NCBI
40	Bekker-Méndez C, Guzmán-Aguilar RM, Hernández-Cueto MA, Huerta-Yepez S, Jarillo-Luna RA, González-Veyrand E and González-Bonilla CR: TUNEL-positive cells in the surgical border of an amputation due to infected diabetic foot. Mol Med Rep. 5:363–372. 2012.PubMed/NCBI
41	Ji F, Zhang H, Wang Y, Li M, Xu W, Kang Y, Wang Z, Wang Z, Cheng P, Tong D, et al: MicroRNA-133a, downregulated in osteosarcoma, suppresses proliferation and promotes apoptosis by targeting Bcl-xL and Mcl-1. Bone. 56:220–226. 2013. View Article : Google Scholar : PubMed/NCBI
42	Zhang H, Cai X, Wang Y, Tang H, Tong D and Ji F: microRNA-143, down-regulated in osteosarcoma, promotes apoptosis and suppresses tumorigenicity by targeting Bcl-2. Oncol Rep. 24:1363–1369. 2010.PubMed/NCBI
43	Zhu S, Wu H, Wu F, Nie D, Sheng S and Mo YY: MicroRNA-21 targets tumor suppressor genes in invasion and metastasis. Cell Res. 18:350–359. 2008. View Article : Google Scholar : PubMed/NCBI
44	Zhu S, Si ML, Wu H and Mo YY: MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem. 282:14328–14336. 2007. View Article : Google Scholar : PubMed/NCBI
45	Gorlick R: Current concepts on the molecular biology of osteosarcoma. Cancer Treat Res. 152:467–478. 2009. View Article : Google Scholar : PubMed/NCBI
46	Bacci G, Bertoni F, Longhi A, Ferrari S, Forni C, Biagini R, Bacchini P, Donati D, Manfrini M, Bernini G and Lari S: Neoadjuvant chemotherapy for high-grade central osteosarcoma of the extremity. Histologic response to preoperative chemotherapy correlates with histologic subtype of the tumor. Cancer. 97:3068–3075. 2003. View Article : Google Scholar : PubMed/NCBI
47	Jianwei Z, Fan L, Xiancheng L, Enzhong B, Shuai L and Can L: MicroRNA 181a improves proliferation and invasion, suppresses apoptosis of osteosarcoma cell. Tumour Biol. 34:3331–3337. 2013. View Article : Google Scholar : PubMed/NCBI