MicroRNA-874 inhibits cell proliferation and invasion by targeting cyclin‑dependent kinase 9 in osteosarcoma

Tang,Wei; Wang,Weiguang; Zhao,Yuchi; Zhao,Zhongyuan

doi:10.3892/ol.2018.8294

MicroRNA-874 inhibits cell proliferation and invasion by targeting cyclin‑dependent kinase 9 in osteosarcoma

Authors:
- Wei Tang
- Weiguang Wang
- Yuchi Zhao
- Zhongyuan Zhao
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Affiliations: Department of Orthopedics, Yantaishan Hospital, Yantai, Shandong 264000, P.R. China
Published online on: March 19, 2018 https://doi.org/10.3892/ol.2018.8294
Pages: 7649-7654
Copyright: © Tang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

MicroRNAs (miRNAs) perform important roles in the development and progression of human malignancy. miR‑874, as a tumor suppressor, is decreased in malignant tumors, including osteosarcoma. However, the potential mechanism of miR‑874 in osteosarcoma remains largely unknown. In the present study, a dual‑luciferase reporter system supported cyclin‑dependent kinase 9 (CDK9) as a direct target gene of miR‑874. miR‑874 mimics evidently repressed CDK9 expression in osteosarcoma. Furthermore, osteosarcoma tissues and cell lines exhibited increased expression of CDK9, and CDK9 expression levels were inversely correlated (R=‑0.725) with that of miR‑874 in osteosarcoma tissues. Finally, CDK9 overexpression reversed the potential effect of miR‑874 on the proliferation and invasion of osteosarcoma cells. Overall, the results revealed that miR‑874, as a tumor suppressor, is involved in osteosarcoma progression and metastasis by targeting CDK9, indicating that the miR-874/CDK9 pathway may serve as a potential therapeutic target for the treatment of osteosarcoma.

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1	Sun XH, Geg XL, Zhang J and Zhang C: miRNA-646 suppresses osteosarcoma cell metastasis by downregulating fibroblast growth factor 2 (FGF2). Tumour Biol. 36:2127–2134. 2015. View Article : Google Scholar : PubMed/NCBI
2	Yang J and Zhang W: New molecular insights into osteosarcoma targeted therapy. Curr Opin Oncol. 25:398–406. 2013. View Article : Google Scholar : PubMed/NCBI
3	Han K, Zhao T, Chen X, Bian N, Yang T, Ma Q, Cai C, Fan Q, Zhou Y and Ma B: microRNA-194 suppresses osteosarcoma cell proliferation and metastasis in vitro and in vivo by targeting CDH2 and IGF1R. Int J Oncol. 45:1437–1449. 2014. View Article : Google Scholar : PubMed/NCBI
4	Sun K and Lai EC: Adult-specific functions of animal microRNAs. Nat Rev Genet. 14:535–548. 2013. View Article : Google Scholar : PubMed/NCBI
5	Li X, Yang H, Tian Q, Liu Y and Weng Y: Upregulation of microRNA-17-92 cluster associates with tumor progression and prognosis in osteosarcoma. Neoplasma. 61:453–460. 2014. View Article : Google Scholar : PubMed/NCBI
6	Wang G, Shen N, Cheng L, Lin J and Li K: Downregulation of miR-22 acts as an unfavorable prognostic biomarker in osteosarcoma. Tumour Biol. 36:7891–7895. 2015. View Article : Google Scholar : PubMed/NCBI
7	Pencheva N and Tavazoie SF: Control of metastatic progression by microRNA regulatory networks. Nat Cell Biol. 15:546–554. 2013. View Article : Google Scholar : PubMed/NCBI
8	Wang L, Gao W, Hu F, Xu Z and Wang F: MicroRNA-874 inhibits cell proliferation and induces apoptosis in human breast cancer by targeting CDK9. FEBS Lett. 588:4527–4535. 2014. View Article : Google Scholar : PubMed/NCBI
9	Zhang X, Tang J, Zhi X, Xie K, Wang W, Li Z, Zhu Y, Yang L, Xu H and Xu Z: miR-874 functions as a tumor suppressor by inhibiting angiogenesis through STAT3/VEGF-A pathway in gastric cancer. Oncotarget. 6:1605–1617. 2015.PubMed/NCBI
10	Nohata N, Hanazawa T, Kikkawa N, Sakurai D, Fujimura L, Chiyomaru T, Kawakami K, Yoshino H, Enokida H, Nakagawa M, et al: Tumour suppressive microRNA-874 regulates novel cancer networks in maxillary sinus squamous cell carcinoma. Br J Cancer. 105:833–841. 2011. View Article : Google Scholar : PubMed/NCBI
11	Kesanakurti D, Maddirela DR, Chittivelu S, Rao JS and Chetty C: Suppression of tumor cell invasiveness and in vivo tumor growth by microRNA-874 in non-small cell lung cancer. Biochem Biophys Res Commun. 434:627–633. 2013. View Article : Google Scholar : PubMed/NCBI
12	Nohata N, Hanazawa T, Kinoshita T, Inamine A, Kikkawa N, Itesako T, Yoshino H, Enokida H, Nakagawa M, Okamoto Y and Seki N: Tumour-suppressive microRNA-874 contributes to cell proliferation through targeting of histone deacetylase 1 in head and neck squamous cell carcinoma. Br J Cancer. 108:1648–1658. 2013. View Article : Google Scholar : PubMed/NCBI
13	Jiang B, Li Z, Zhang W, Wang H, Zhi X, Feng J, Chen Z, Zhu Y, Yang L, Xu H and Xu Z: miR-874 inhibits cell proliferation, migration and invasion through targeting aquaporin-3 in gastric cancer. J Gastroenterol. 49:1011–1025. 2014. View Article : Google Scholar : PubMed/NCBI
14	Zhang LQ, Sun SL, Li WY, Feng Z, Xu XY, Zhuang QS and Fang J: Decreased expression of tumor suppressive miR-874 and its clinical significance in human osteosarcoma. Genet Mol Res. 14:18315–18324. 2015. View Article : Google Scholar : PubMed/NCBI
15	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
16	Garriga J, Bhattacharya S, Calbó J, Marshall RM, Truongcao M, Haines DS and Graña X: CDK9 is constitutively expressed throughout the cell cycle, and its steady-state expression is independent of SKP2. Mol Cell Biol. 23:5165–5173. 2003. View Article : Google Scholar : PubMed/NCBI
17	Gordon V, Bhadel S, Wunderlich W, Zhang J, Ficarro SB, Mollah SA, Shabanowitz J, Hunt DF, Xenarios I, Hahn WC, et al: CDK9 regulates AR promoter selectivity and cell growth through serine 81 phosphorylation. Mol Endocrinol. 24:2267–2280. 2010. View Article : Google Scholar : PubMed/NCBI
18	Krystof V, Baumli S and Fürst R: Perspective of cyclin-dependent kinase 9 (CDK9) as a drug target. Curr Pharm Des. 18:2883–2890. 2012. View Article : Google Scholar : PubMed/NCBI
19	Mitra P, Yang RM, Sutton J, Ramsay RG and Gonda TJ: CDK9 inhibitors selectively target estrogen receptor-positive breast cancer cells through combined inhibition of MYB and MCL-1 expression. Oncotarget. 23:9069–9083. 2016.
20	Morales F and Giordano A: Overview of CDK9 as a target in cancer research. Cell Cycle. 15:519–527. 2016. View Article : Google Scholar : PubMed/NCBI
21	Yin T, Lallena MJ, Kreklau EL, Fales KR, Carballares S, Torrres R, Wishart GN, Ajamie RT, Cronier DM, Iversen PW, et al: A novel CDK9 inhibitor shows potent antitumor efficacy in preclinical hematologic tumor models. Mol Cancer Ther. 13:1442–1456. 2014. View Article : Google Scholar : PubMed/NCBI
22	Liu X, Shi S, Lam F, Pepper C, Fischer PM and Wang S: CDKI-71, a novel CDK9 inhibitor, is preferentially cytotoxic to cancer cells compared to flavopiridol. Int J Cancer. 130:1216–1226. 2012. View Article : Google Scholar : PubMed/NCBI