Overexpression of miR‑20a promotes the progression of osteosarcoma by directly targeting QKI2

Yang,Hongbo; Li,Yongli; Peng,Zhibin; Wang,Yansong

doi:10.3892/ol.2019.10313

Overexpression of miR‑20a promotes the progression of osteosarcoma by directly targeting QKI2

Authors:
- Hongbo Yang
- Yongli Li
- Zhibin Peng
- Yansong Wang
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Affiliations: Department of Orthopedic Surgery, Affiliated Hospital of Chifeng University, Chifeng, Inner Mongolia 024000, P.R. China, Department of Tumor Radiotherapy, Heilongjiang Provincial Hospital, Harbin, Heilongjiang 150000, P.R. China, Department of Orthopedic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
Published online on: May 3, 2019 https://doi.org/10.3892/ol.2019.10313
Pages: 87-94
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteosarcoma (OS) is the most common type of malignant primary bone neoplasm. Although the application of neoadjuvant chemotherapy has improved the 5‑year survival rate of patients suffering from OS, prognosis remains poor. Therefore, it is important to elucidate the molecular mechanisms underlying the occurrence, progression and metastasis of OS. The RNA‑binding protein Quaking (QKI) is a member of the STAR family of proteins, and can function as a tumor suppressor gene to suppress the occurrence and progression of a variety of tumors; however, the role of QKI in OS remains to be fully elucidated. In the present study, it was identified that the expression of QKI2 was downregulated in OS using western blot analysis. In addition, subsequent functional investigations, including MTT, Transwell invasion and migration assays, revealed that QKI2 inhibited the proliferation, invasion and migration of an OS cell line in vitro. By implementing a series of experimental techniques in molecular biology, including reverse transcription‑quantitative polymerase chain reaction and a double fluorescence reporter assay, it was demonstrated that the expression of miR‑20a was high and inhibited the expression of QKI2 in OS. In conclusion, it was revealed that aberrantly upregulated miR‑20a inhibited the expression of QKI2 in OS by targeting QKI2 mRNA, subsequently promoting the proliferation, migration and invasion of OS cells.

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1	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
2	Longhi A, Errani C, De Paolis M, Mercuri M and Bacci G: Primary bone osteosarcoma in the pediatric age: State of the art. Cancer Treat Rev. 32:423–436. 2006. View Article : Google Scholar : PubMed/NCBI
3	Friebele JC, Peck J, Pan X, Abdel-Rasoul M and Mayerson JL: Osteosarcoma: A meta-analysis and review of the literature. Am J Orthop (Belle Mead NJ). 44:547–553. 2015.PubMed/NCBI
4	Kondo T, Furuta T, Mitsunaga K, Ebersole TA, Shichiri M, Wu J, Artzt K, Yamamura K and Abe K: Genomic organization and expression analysis of the mouse qkI locus. Mamm Genome. 10:662–669. 1999.PubMed/NCBI
5	Galarneau A and Richard S: Target RNA motif and target mRNAs of the Quaking STAR protein. Nat Struct Mol Biol. 12:691–698. 2005. View Article : Google Scholar : PubMed/NCBI
6	Zhang Y, Lu Z, Ku L, Chen Y, Wang H and Feng Y: Tyrosine phosphorylation of QKI mediates developmental signals to regulate mRNA metabolism. EMBO J. 22:1801–1810. 2003. View Article : Google Scholar : PubMed/NCBI
7	Yu F, Jin L, Yang G, Ji L, Wang F and Lu Z: Post-transcriptional repression of FOXO1 by QKI results in low levels of FOXO1 expression in breast cancer cells. Oncol Rep. 31:1459–1465. 2014. View Article : Google Scholar : PubMed/NCBI
8	Ichimura K, Mungall AJ, Fiegler H, Pearson DM, Dunham I, Carter NP and Collins VP: Small regions of overlapping deletions on 6q26 in human astrocytic tumours identified using chromosome 6 tile path array-CGH. Oncogene. 25:1261–1271. 2006. View Article : Google Scholar : PubMed/NCBI
9	Li ZZ, Kondo T, Murata T, Ebersole TA, Nishi T, Tada K, Ushio Y, Yamamura K and Abe K: Expression of Hqk encoding a KH RNA binding protein is altered in human glioma. Jpn J Cancer Res. 93:167–177. 2002. View Article : Google Scholar : PubMed/NCBI
10	Mulholland PJ, Fiegler H, Mazzanti C, Gorman P, Sasieni P, Adams J, Jones TA, Babbage JW, Vatcheva R, Ichimura K, et al: Genomic profiling identifies discrete deletions associated with translocations in glioblastoma multiforme. Cell Cycle. 5:783–791. 2006. View Article : Google Scholar : PubMed/NCBI
11	Yin D, Ogawa S, Kawamata N, Tunici P, Finocchiaro G, Eoli M, Ruckert C, Huynh T, Liu G, Kato M, et al: High-resolution genomic copy number profiling of glioblastoma multiforme by single nucleotide polymorphism DNA microarray. Mol Cancer Res. 7:665–677. 2009. View Article : Google Scholar : PubMed/NCBI
12	Fu X and Feng Y: QKI-5 suppresses cyclin D1 expression and proliferation of oral squamous cell carcinoma cells via MAPK signalling pathway. Int J Oral Maxillofac Surg. 44:562–567. 2015. View Article : Google Scholar : PubMed/NCBI
13	Bian Y, Wang L, Lu H, Yang G, Zhang Z, Fu H, Lu X, Wei M, Sun J, Zhao Q, et al: Downregulation of tumor suppressor QKI in gastric cancer and its implication in cancer prognosis. Biochem Biophys Res Commun. 422:187–193. 2012. View Article : Google Scholar : PubMed/NCBI
14	Yang G, Fu H, Zhang J, Lu X, Yu F, Jin L, Bai L, Huang B, Shen L, Feng Y, et al: RNA-binding protein quaking, a critical regulator of colon epithelial differentiation and a suppressor of colon cancer. Gastroenterology. 138:231–240.e1-5. 2010. View Article : Google Scholar : PubMed/NCBI
15	Chen AJ, Paik JH, Zhang H, Shukla SA, Mortensen R, Hu J, Ying H, Hu B, Hurt J, Farny N, et al: STAR RNA-binding protein Quaking suppresses cancer via stabilization of specific miRNA. Genes Dev. 26:1459–1472. 2012. View Article : Google Scholar : PubMed/NCBI
16	Mendell JT: miRiad roles for the miR-17-92 cluster in development and disease. Cell. 133:217–222. 2008. View Article : Google Scholar : PubMed/NCBI
17	Jafarzadeh-Samani Z, Sohrabi S, Shirmohammadi K, Effatpanah H, Yadegarazari R and Saidijam M: Evaluation of miR-22 and miR-20a as diagnostic biomarkers for gastric cancer. Chin Clin Oncol. 6:162017. View Article : Google Scholar : PubMed/NCBI
18	Zhang H, Mao F, Shen T, Luo Q, Ding Z, Qian L and Huang J: Plasma miR-145, miR-20a, miR-21 and miR-223 as novel biomarkers for screening early-stage non-small cell lung cancer. Oncol Lett. 13:669–676. 2017. View Article : Google Scholar : PubMed/NCBI
19	Babu KR and Muckenthaler MU: miR-20a regulates expression of the iron exporter ferroportin in lung cancer. J Mol Med (Berl). 94:347–359. 2016. View Article : Google Scholar : PubMed/NCBI
20	Peng J, Thakur A, Zhang S, Dong Y, Wang X, Yuan R, Zhang K and Guo X: Expressions of miR-181a and miR-20a in RPMI8226 cell line and their potential as biomarkers for multiple myeloma. Tumour Biol. 36:8545–8552. 2015. View Article : Google Scholar : PubMed/NCBI
21	Sokolova V, Fiorino A, Zoni E, Crippa E, Reid JF, Gariboldi M and Pierotti MA: The effects of miR-20a on p21: Two mechanisms blocking growth arrest in TGF-β-responsive colon carcinoma. J Cell Physiol. 230:3105–3114. 2015. View Article : Google Scholar : PubMed/NCBI
22	Pesta M, Klecka J, Kulda V, Topolcan O, Hora M, Eret V, Ludvikova M, Babjuk M, Novak K, Stolz J and Holubec L: Importance of miR-20a expression in prostate cancer tissue. Anticancer Res. 30:3579–3583. 2010.PubMed/NCBI
23	Chang Y, Liu C, Yang J, Liu G, Feng F, Tang J, Hu L, Li L, Jiang F, Chen C, et al: MiR-20a triggers metastasis of gallbladder carcinoma. J Hepatol. 59:518–527. 2013. View Article : Google Scholar : PubMed/NCBI
24	Namløs HM, Meza-Zepeda LA, Barøy T, Østensen IH, Kresse SH, Kuijjer ML, Serra M, Bürger H, Cleton-Jansen AM and Myklebost O: Modulation of the osteosarcoma expression phenotype by microRNAs. PLoS One. 7:e480862012. View Article : Google Scholar : PubMed/NCBI
25	Arabi L, Gsponer JR, Smida J, Nathrath M, Perrina V, Jundt G, Ruiz C, Quagliata L and Baumhoer D: Upregulation of the miR-17-92 cluster and its two paraloga in osteosarcoma - reasons and consequences. Genes Cancer. 5:56–63. 2014.PubMed/NCBI
26	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
27	Wu PK, Chen WM, Chen CF, Lee OK, Haung CK and Chen TH: Primary osteogenic sarcoma with pulmonary metastasis: Clinical results and prognostic factors in 91 patients. Jpn J Clin Oncol. 39:514–522. 2009. View Article : Google Scholar : PubMed/NCBI
28	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
29	Costa FF: Non-coding RNAs, epigenetics and complexity. Gene. 410:9–17. 2008. View Article : Google Scholar : PubMed/NCBI
30	Bartel DP: MicroRNAs: Target recognition and regulatory functions. Cell. 136:215–233. 2009. View Article : Google Scholar : PubMed/NCBI
31	Sun J, Liu HP, Deng JE and Zhou M: Systematic analysis of genomic organization and heterogeneities of miRNA cluster in vertebrates. Mol Biol Rep. 39:5143–5149. 2012. View Article : Google Scholar : PubMed/NCBI
32	Wang QH, Zhou M, Sun J, Ning SW, Li Y, Chen L, Zheng Y and Li X, Lv SL and Li X: Systematic analysis of human microRNA divergence based on evolutionary emergence. FEBS Lett. 585:240–248. 2011. View Article : Google Scholar : PubMed/NCBI
33	Zhou M, Wang Q, Sun J, Li X, Xu L, Yang H, Shi H, Ning S, Chen L, Li Y, et al: In silico detection and characteristics of novel microRNA genes in the Equus caballus genome using an integrated ab initio and comparative genomic approach. Genomics. 94:125–131. 2009. View Article : Google Scholar : PubMed/NCBI
34	Hwang HW and Mendell JT: MicroRNAs in cell proliferation, cell death, and tumorigenesis. Br J Cancer. 94:776–780. 2006. View Article : Google Scholar : PubMed/NCBI
35	Passetti F, Ferreira CG and Costa FF: The impact of microRNAs and alternative splicing in pharmacogenomics. Pharmacogenomics J. 9:1–13. 2009. View Article : Google Scholar : PubMed/NCBI
36	Chen CZ: MicroRNAs as oncogenes and tumor suppressors. N Engl J Med. 353:1768–1771. 2005. View Article : Google Scholar : PubMed/NCBI
37	Wang Z, Wang B, Shi Y, Xu C, Xiao HL, Ma LN, Xu SL, Yang L, Wang QL, Dang WQ, et al: Oncogenic miR-20a and miR-106a enhance the invasiveness of human glioma stem cells by directly targeting TIMP-2. Oncogene. 34:1407–1419. 2015. View Article : Google Scholar : PubMed/NCBI
38	Zhang RL, Yang JP, Peng LX, Zheng LS, Xie P, Wang MY, Cao Y, Zhang ZL, Zhou FJ, Qian CN and Bao YX: RNA-binding protein QKI-5 inhibits the proliferation of clear cell renal cell carcinoma via post-transcriptional stabilization of RASA1 mRNA. Cell Cycle. 15:3094–3104. 2016. View Article : Google Scholar : PubMed/NCBI
39	de Miguel FJ, Pajares MJ, Martínez-Terroba E, Ajona D, Morales X, Sharma RD, Pardo FJ, Rouzaut A, Rubio A, Montuenga LM and Pio R: A large-scale analysis of alternative splicing reveals a key role of QKI in lung cancer. Mol Oncol. 10:1437–1449. 2016. View Article : Google Scholar : PubMed/NCBI