miR-34a is downregulated in human osteosarcoma stem-like cells and promotes invasion, tumorigenic ability and self-renewal capacity Retraction in /10.3892/mmr.2024.13196

Zou,Yonggen; Huang,Yuanshuai; Yang,Jiexiang; Wu,Jian; Luo,Cheng

doi:10.3892/mmr.2017.6187

miR-34a is downregulated in human osteosarcoma stem-like cells and promotes invasion, tumorigenic ability and self-renewal capacity

Retraction in 10.3892/mmr.2024.13196

Authors:
- Yonggen Zou
- Yuanshuai Huang
- Jiexiang Yang
- Jian Wu
- Cheng Luo
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Affiliations: Department of Orthopedics, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, Department of Transfusion, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
Published online on: February 9, 2017 https://doi.org/10.3892/mmr.2017.6187
Pages: 1631-1637
Copyright: © Zou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

MicroRNA-34 (miR-34), in particular miR-34a, has a negative regulatory effect on osteosarcoma cell proliferation, migration and invasion. Notably, it is also a post‑transcriptional regulatory factor of (sex determining region Y)‑box 2 (Sox-2), which is required for osteosarcoma cell self‑renewal and tumorigenesis. As a direct regulator of Sox‑2, miR‑34a has been hypothesized to be greatly associated with the regulation of malignancies in osteosarcoma. To investigate the role of miR-34a in the malignancies of osteosarcoma, reverse transcription‑quantitative polymerase chain reaction was performed to detect the expression level of miR‑34a in osteospheres. The results revealed that the miR‑34a, b and c were suppressed in osteosarcoma stem‑like cells (OSCs) and osteospheres. The introduction of miR‑34a mimics and short hairpin (sh)RNA targeting Sox‑2 mRNA (shSox‑2) in human OSCs markedly reduced their transformation properties in vitro and their capacity to form tumors in soft agar. Furthermore, the epigenetic expression of miR‑34a and shSox‑2 inhibited the expression of the stem cell marker, stem cell antigen‑1 and led to the failure of osteosphere formation, respectively. The data of the present study indicated that the inhibitory role of miR‑34a on tumor growth and metastasis of osteosarcoma may function by reducing the maintenance of osteosphere self‑renewal capacity, elimination of tumorigenic ability and invasion of osteosarcoma in vitro. These findings may provide the basis for a novel therapeutic target of osteosarcomas based on inducing the expression of miR-34a.

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1	Ek ET, Dass CR and Choong PF: Commonly used mouse models of osteosarcoma. Crit Rev Oncol Hematol. 60:1–8. 2006. View Article : Google Scholar : PubMed/NCBI
2	Meyers PA, Schwartz CL, Krailo MD, Healey JH, Bernstein ML, Betcher D, Ferquson WS, Gebhardt MC, Goorin AM, Harris M, et al: Osteosarcoma: The addition of muramyl tripeptide to chemotherapy improves overall survival-a report from the Children's oncology group. J Clin Oncol. 26:633–638. 2008. View Article : Google Scholar : PubMed/NCBI
3	Ma Y, Ren Y, Han EQ, Li H, Chen D, Jacobs JJ, Gitelis S, O'Keefe RJ, Konttinen YT, Yin G and Li TF: Inhibition of the Wnt-β-catenin and Notch signaling pathways sensitizes osteosarcoma cells to chemotherapy. Biochem Biophys Res Commun. 431:274–279. 2013. View Article : Google Scholar : PubMed/NCBI
4	Zhang Y, Duan G and Feng S: MicroRNA-301a modulates doxorubicin resistance in osteosarcoma cells by targeting AMP-activated protein kinase alpha 1. Biochem Biophys Res Commun. 459:367–373. 2015. View Article : Google Scholar : PubMed/NCBI
5	Clarke MF: Self-renewal and solid-tumor stem cells. Biol Blood Marrow Transplant. 11(2 Suppl 2): S14–S16. 2005. View Article : Google Scholar
6	Ambros V: microRNAs: Tiny regulators with great potential. Cell. 107:823–826. 2001. View Article : Google Scholar : PubMed/NCBI
7	Lewis BP, Burge CB and Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 120:15–20. 2005. View Article : Google Scholar : PubMed/NCBI
8	Krutovskikh VA and Herceg Z: Oncogenic miroRNAs (OncomiRs) as a new class of cancer biomarkers. Bioessays. 32:894–904. 2010. View Article : Google Scholar : PubMed/NCBI
9	Lee YS and Dutta A: MicroRNAs in cancer. Annu Rev Pathol. 4:199–227. 2009. View Article : Google Scholar : PubMed/NCBI
10	Baashah S and Soleimani M: The oncogenic and tumour suppressive roles of microRNAs in cancer and apoptosis. Eur J Cancer. 47:1127–1137. 2011. View Article : Google Scholar : PubMed/NCBI
11	He L, He X, Lim LP, De Stanchina E, Xuan Z, Liang Y, Xue W, Zender L, Magnus J, Ridzon D, et al: A microRNA component of the p53 tumour suppressor network. Nature. 447:1130–1134. 2007. View Article : Google Scholar : PubMed/NCBI
12	Hermeking H: p53 enters the microRNA world. Cancer Cell. 12:414–418. 2007. View Article : Google Scholar : PubMed/NCBI
13	Yan K, Gao J, Yang T, Ma Q, Qiu X, Fan Q and Ma B: MicroRNA-34a inhibits the proliferation and metastasis of osteosarcoma cells both in vitro and in vivo. PLoS One. 7:e337782012. View Article : Google Scholar : PubMed/NCBI
14	Avilion AA, Nicolis SK, Pevny LH, Perez L, Vivian N and Lovell-Badge R: Multipotent cell lineages in early mouse development depend on SOX2 function. Genes Dev. 17:126–140. 2003. View Article : Google Scholar : PubMed/NCBI
15	Lefebvre V, Dumitriu B, Penzo-Méndez A, Han Y and Pallavi B: Control of cell fate and differentiation by Sry-related high-mobility-group box (Sox) transcription factors. Int J Biochem Cell Biol. 39:2195–2214. 2007. View Article : Google Scholar : PubMed/NCBI
16	Basu-Roy U, Seo E, Ramanathapuram L, Rapp TB, Perry JA, Orkin SH, Mansukhani A and Basilico C: Sox2 maintains self-renewal of tumor-initiating cells in osteosarcomas. Oncogene. 31:2270–2282. 2012. View Article : Google Scholar : PubMed/NCBI
17	Gritti A, Frölichsthal-Schoeller P, Galli R, Parati EA, Cova L, Pagano SF, Bjornson CR and Vescovi AL: Epidermal and fibroblast growth factors behave as mitogenic regulators for a single multipotent stem cell-like population from the subventricular region of the adult mouse forebrain. J Neurosci. 19:3287–3297. 1999.PubMed/NCBI
18	Vanderluit JL, Ferguson KL, Nikoletopoulou V, Parker M, Ruzhynsky V, Alexson T, McNamara SM, Park DS, Rudnicki M and Slack RS: p107 regulates neural precursor cells in the mammalian brain. J Cell Biol. 166:853–863. 2004. View Article : Google Scholar : PubMed/NCBI
19	Deng S, Calin GA, Croce CM, Coukos G and Zhang L: Mechanisms of microRNA deregulation in human cancer. Cell Cycle. 7:2643–2646. 2008. View Article : Google Scholar : PubMed/NCBI
20	Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, Labourier E, Reinert KL, Brown D and Slack FJ: RAS is regulated by the let-7 microRNA family. Cell. 120:635–647. 2005. View Article : Google Scholar : PubMed/NCBI
21	Saito Y, Liang G, Egger G, Friedman JM, Chuang JC, Coetzee GA and Jones PA: Specific activation of microRNA-127 with downregulation of the proto-oncogen BCL6 by chromatin-modifying drugs in human cancer cells. Cancer Cell. 9:435–443. 2006. View Article : Google Scholar : PubMed/NCBI
22	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 over expressed in and has an oncogenic effect on renal cell carcinoma. J Urol. 183:743–751. 2010. View Article : Google Scholar : PubMed/NCBI
23	Basu-Roy U, Ambrosetti D, Favaro R, Nicolis SK, Mansukhani A and Basilico C: The transcription factor Sox2 is required for osteoblast self-renewal. Cell Death Differ. 17:1345–1353. 2010. View Article : Google Scholar : PubMed/NCBI