MicroRNA-493 inhibits the proliferation and invasion of osteosarcoma cells through directly targeting specificity protein 1 Retraction in /10.3892/ol.2023.14160

Qian,Ming; Gong,Haiyi; Yang,Xinghai; Zhao,Jian; Yan,Wangjun; Lou,Yan; Peng,Dongyu; Li ,Zhenxi; Xiao,Jianru

doi:10.3892/ol.2018.8268

MicroRNA-493 inhibits the proliferation and invasion of osteosarcoma cells through directly targeting specificity protein 1

Retraction in: /10.3892/ol.2023.14160

Authors:
- Ming Qian
- Haiyi Gong
- Xinghai Yang
- Jian Zhao
- Wangjun Yan
- Yan Lou
- Dongyu Peng
- Zhenxi Li
- Jianru Xiao
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Affiliations: Bone Tumor Center, Changzheng Hospital, Second Military Medical University, Huangpu, Shanghai 200003, P.R. China
Published online on: March 15, 2018 https://doi.org/10.3892/ol.2018.8268
Pages: 8149-8156

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Abstract

Osteosarcoma (OS) is the most common type of primary bone tumor and accounts for ~60% of all malignant bone tumors in children and adolescents. A large number of studies have proposed that the dysregulated and dysfunctional microRNAs may serve important roles in the occurrence, progression and metastasis of various types of human cancer, including OS. MicroRNA‑493 (miR‑493) has been identified to act as a tumor suppressor in several types of human cancer. However, little is known regarding the expression pattern and clinical significance of miR‑493 in OS. In the present study, reverse transcription‑quantitative polymerase chain reaction analysis revealed that miR‑493 was markedly downregulated in OS tissues and cell lines and a low miR‑493 level were associated with distant metastasis and clinical stage. Furthermore, functional experiments demonstrated that enforced expression of miR‑493 led to a significant decrease in OS cell proliferation and invasion in vitro. Furthermore, through bioinformatics analysis, specificity protein 1 (SP1) was identified as a direct target gene of miR‑493 in OS. Its expression was upregulated in OS tissues and was negatively associated with miR‑493 expression levels. Inhibition of SP1 expression also suppressed the proliferation and invasion of OS, exerting a similar effect to that induced by miR‑493 overexpression. These results suggested that miR‑493 inhibited OS cell proliferation and invasion through negative regulation of SP1. Therefore, miR‑493/SP1 may represent a potential therapeutic target for the treatment of OS.

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1	Ta HT, Dass CR, Choong PF and Dunstan DE: Osteosarcoma treatment: State of the art. Cancer Metastasis Rev. 28:247–263. 2009. View Article : Google Scholar : PubMed/NCBI
2	Tang J, Shen L, Yang Q and Zhang C: Overexpression of metadherin mediates metastasis of osteosarcoma by regulating epithelial-mesenchymal transition. Cell Prolif. 47:427–434. 2014. View Article : Google Scholar : PubMed/NCBI
3	Tang N, Song WX, Luo J, Haydon RC and He TC: Osteosarcoma development and stem cell differentiation. Clin Orthop Relat Res. 466:2114–2130. 2008. View Article : Google Scholar : PubMed/NCBI
4	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
5	Qureshi A, Ahmad Z, Azam M and Idrees R: Epidemiological data for common bone sarcomas. Asian Pac J Cancer Prev. 11:393–395. 2010.PubMed/NCBI
6	Laschi M, Bernardini G, Geminiani M, Ghezzi L, Amato L, Braconi D, Millucci L, Frediani B, Spreafico A, Franchi A, et al: Establishment of four new human primary cell cultures from chemo-naive italian osteosarcoma patients. J Cell Physiol. 230:2718–2727. 2015. View Article : Google Scholar : PubMed/NCBI
7	Allison DC, Carney SC, Ahlmann ER, Hendifar A, Chawla S, Fedenko A, Angeles C and Menendez LR: A meta-analysis of osteosarcoma outcomes in the modern medical era. Sarcoma. 2012:7048722012. View Article : Google Scholar : PubMed/NCBI
8	Dong J, Liu Y, Liao W, Liu R, Shi P and Wang L: miRNA-223 is a potential diagnostic and prognostic marker for osteosarcoma. J Bone Oncol. 5:74–79. 2016. View Article : Google Scholar : PubMed/NCBI
9	Sun K and Lai EC: Adult-specific functions of animal microRNAs. Nat Rev Genet. 14:535–548. 2013. View Article : Google Scholar : PubMed/NCBI
10	Chen K and Rajewsky N: The evolution of gene regulation by transcription factors and microRNAs. Nat Rev Genet. 8:93–103. 2007. View Article : Google Scholar : PubMed/NCBI
11	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
12	Wang W and Luo YP: MicroRNAs in breast cancer: Oncogene and tumor suppressors with clinical potential. J Zhejiang Univ Sci B. 16:18–31. 2015. View Article : Google Scholar : PubMed/NCBI
13	Yu X and Li Z: The role of miRNAs in cutaneous squamous cell carcinoma. J Cell Mol Med. 20:3–9. 2016. View Article : Google Scholar : PubMed/NCBI
14	Li Z, Lei H, Luo M, Wang Y, Dong L, Ma Y, Liu C, Song W, Wang F, Zhang J, et al: DNA methylation downregulated mir-10b acts as a tumor suppressor in gastric cancer. Gastric Cancer. 18:43–54. 2015. View Article : Google Scholar : PubMed/NCBI
15	Li Z, Yu X, Wang Y, Shen J, Wu WK, Liang J and Feng F: By downregulating TIAM1 expression, microRNA-329 suppresses gastric cancer invasion and growth. Oncotarget. 6:17559–17569. 2015.PubMed/NCBI
16	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
17	Dong W, Li B, Wang J, Song Y, Zhang Z and Fu C: MicroRNA-337 inhibits cell proliferation and invasion of cervical cancer through directly targeting specificity protein 1. Tumour Biol. 39:10104283177113232017. View Article : Google Scholar : PubMed/NCBI
18	Ueno K, Hirata H, Majid S, Yamamura S, Shahryari V, Tabatabai ZL, Hinoda Y and Dahiya R: Tumor suppressor microRNA-493 decreases cell motility and migration ability in human bladder cancer cells by downregulating RhoC and FZD4. Mol Cancer Ther. 11:244–253. 2012. View Article : Google Scholar : PubMed/NCBI
19	Gu Y, Cheng Y, Song Y, Zhang Z, Deng M, Wang C, Zheng G and He Z: MicroRNA-493 suppresses tumor growth, invasion and metastasis of lung cancer by regulating E2F1. PLoS One. 9:e1026022014. View Article : Google Scholar : PubMed/NCBI
20	Zhou W, Zhang C, Jiang H, Zhang Z, Xie L and He X: miR-493 suppresses the proliferation and invasion of gastric cancer cells by targeting RhoC. Iran J Basic Med Sci. 18:1027–1033. 2015.PubMed/NCBI
21	Okamoto K, Ishiguro T, Midorikawa Y, Ohata H, Izumiya M, Tsuchiya N, Sato A, Sakai H and Nakagama H: miR-493 induction during carcinogenesis blocks metastatic settlement of colon cancer cells in liver. EMBO J. 31:1752–1763. 2012. View Article : Google Scholar : PubMed/NCBI
22	Tambe M, Pruikkonen S, Maki-Jouppila J, Chen P, Elgaaen BV, Straume AH, Huhtinen K, Cárpen O, Lønning PE, Davidson B, et al: Novel Mad2-targeting miR-493-3p controls mitotic fidelity and cancer cells' sensitivity to paclitaxel. Oncotarget. 7:12267–12285. 2016. View Article : Google Scholar : PubMed/NCBI
23	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
24	Black AR, Black JD and Azizkhan-Clifford J: Sp1 and kruppel-like factor family of transcription factors in cell growth regulation and cancer. J Cell Physiol. 188:143–160. 2001. View Article : Google Scholar : PubMed/NCBI
25	Li L, He S, Sun JM and Davie JR: Gene regulation by Sp1 and Sp3. Biochem Cell Biol. 82:460–471. 2004. View Article : Google Scholar : PubMed/NCBI
26	Mukhopadhyay D and Datta K: Multiple regulatory pathways of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) expression in tumors. Semin Cancer Biol. 14:123–130. 2004. View Article : Google Scholar : PubMed/NCBI
27	Sampson VB, Yoo S, Kumar A, Vetter NS and Kolb EA: MicroRNAs and potential targets in osteosarcoma: Review. Front Pediatr. 3:692015. View Article : Google Scholar : PubMed/NCBI
28	Sun HB, Chen X, Ji H, Wu T, Lu HW, Zhang Y, Li H and Li YM: miR494 is an independent prognostic factor and promotes cell migration and invasion in colorectal cancer by directly targeting PTEN. Int J Oncol. 45:2486–2494. 2014. View Article : Google Scholar : PubMed/NCBI
29	Li Y, Zeng C, Tu M, Jiang W, Dai Z, Hu Y, Deng Z and Xiao W: MicroRNA-200b acts as a tumor suppressor in osteosarcoma via targeting ZEB1. Onco Targets Ther. 9:3101–3111. 2016.PubMed/NCBI
30	Yin Z, Ding H, He E, Chen J and Li M: Up-regulation of microRNA-491-5p suppresses cell proliferation and promotes apoptosis by targeting FOXP4 in human osteosarcoma. Cell Prolif. 2016.
31	Song L, Yang J, Duan P, Xu J, Luo X, Luo F, Zhang Z, Hou T, Liu B and Zhou Q: MicroRNA-24 inhibits osteosarcoma cell proliferation both in vitro and in vivo by targeting LPAATbeta. Arch Biochem Biophys. 535:128–135. 2013. View Article : Google Scholar
32	Wu X, Zhong D, Gao Q, Zhai W, Ding Z and Wu J: MicroRNA-34a inhibits human osteosarcoma proliferation by downregulating ether a go-go 1 expression. Int J Med Sci. 10:676–682. 2013. View Article : Google Scholar : PubMed/NCBI
33	Dynan WS and Tjian R: The promoter-specific transcription factor Sp1 binds to upstream sequences in the SV40 early promoter. Cell. 35:79–87. 1983. View Article : Google Scholar : PubMed/NCBI
34	Chang WC and Hung JJ: Functional role of post-translational modifications of Sp1 in tumorigenesis. J Biomed Sci. 19:942012. View Article : Google Scholar : PubMed/NCBI
35	Davie JR, He S, Li L, Sekhavat A, Espino P, Drobic B, Dunn KL, Sun JM, Chen HY, Yu J, et al: Nuclear organization and chromatin dynamics-Sp1, Sp3 and histone deacetylases. Adv Enzyme Regul. 48:189–208. 2008. View Article : Google Scholar : PubMed/NCBI
36	Pathi S, Jutooru I, Chadalapaka G, Nair V, Lee SO and Safe S: Aspirin inhibits colon cancer cell and tumor growth and downregulates specificity protein (Sp) transcription factors. PLoS One. 7:e482082012. View Article : Google Scholar : PubMed/NCBI
37	Chintharlapalli S, Papineni S, Ramaiah SK and Safe S: Betulinic acid inhibits prostate cancer growth through inhibition of specificity protein transcription factors. Cancer Res. 67:2816–2823. 2007. View Article : Google Scholar : PubMed/NCBI
38	Mao Y, Chen H, Lin Y, Xu X, Hu Z, Zhu Y, Wu J, Xu X, Zheng X and Xie L: microRNA-330 inhibits cell motility by downregulating Sp1 in prostate cancer cells. Oncol Rep. 30:327–333. 2013. View Article : Google Scholar : PubMed/NCBI
39	Deacon K, Onion D, Kumari R, Watson SA and Knox AJ: Elevated SP-1 transcription factor expression and activity drives basal and hypoxia-induced vascular endothelial growth factor (VEGF) expression in non-small cell lung cancer. J Biol Chem. 287:39967–39981. 2012. View Article : Google Scholar : PubMed/NCBI
40	Wang L, Wei D, Huang S, Peng Z, Le X, Wu TT, Yao J, Ajani J and Xie K: Transcription factor Sp1 expression is a significant predictor of survival in human gastric cancer. Clin Cancer Res. 9:6371–6380. 2003.PubMed/NCBI