Restoration of microRNA‑130b expression suppresses osteosarcoma cell malignant behavior in vitro

Wu,Yi; Sun,Wei; Kong,Ying; Liu,Bo; Zeng,Ming; Wang,Wanchun

doi:10.3892/ol.2018.8643

July-2018 Volume 16 Issue 1

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July-2018 Volume 16 Issue 1

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Article Open Access

Restoration of microRNA‑130b expression suppresses osteosarcoma cell malignant behavior in vitro

Authors:
- Yi Wu
- Wei Sun
- Ying Kong
- Bo Liu
- Ming Zeng
- Wanchun Wang
View Affiliations / Copyright

Affiliations: Department of Orthopedics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China

Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Pages: 97-104
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Published online on: May 7, 2018

https://doi.org/10.3892/ol.2018.8643
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Abstract

The alteration of microRNA (miR)‑130b expression has been associated with promoting or suppressing numerous types of human cancer. A previous study evaluated the expression level of miR‑130b in osteosarcoma tissues, and subsequently investigated the effects of miR‑130b on the regulation of osteosarcoma cells malignant behavior in vitro. The study revealed that miR‑130b expression levels were significantly reduced in osteosarcoma tissues and cell lines, compared with in adjacent tissues or normal cell lines. The expression of miR‑130b inhibited the proliferation of osteosarcoma U‑2OS and Saos‑2 cells and impaired their ability to migrate, invade and form colonies. Furthermore, analysis using TargetScan and a dual‑luciferase reporter assay demonstrated that miR‑130b directly interacted with the 3'‑untranslated region of transforming growth factor α (TGFA) and suppressed TGFA expression. TGFA and miR‑130b were also inversely expressed in osteosarcoma tissues. In addition, expression of TGFA was able to alter miR‑130‑regulated osteosarcoma cell proliferation, migration and invasion. Thus, the present study demonstrated that miR‑130b was downregulated in osteosarcoma tissues and cell lines, whereas the expression of miR‑130b suppressed osteosarcoma cell malignant behavior. At the gene level, miR‑130 directly targets and inhibits TGFA expression, in addition to phosphorylated protein kinase B and epidermal growth factor receptor expression levels. Further study is required to evaluate miR‑130b antitumor activity in osteosarcoma.

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1	Biazzo A and De Paolis M: Multidisciplinary approach to osteosarcoma. Acta Orthop Belg. 82:690–698. 2016.PubMed/NCBI
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	Picci P: Osteosarcoma (osteogenic sarcoma). Orphanet J Rare Dis. 2:62007. View Article : Google Scholar : PubMed/NCBI
4	Logue JP and Cairnduff F: Radiation induced extraskeletal osteosarcoma. Br J Radiol. 64:171–172. 1991. View Article : Google Scholar : PubMed/NCBI
5	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
6	Meyers PA, Healey JH, Chou AJ, Wexler LH, Merola PR, Morris CD, Laquaglia MP, Kellick MG, Abramson SJ and Gorlick R: Addition of pamidronate to chemotherapy for the treatment of osteosarcoma. Cancer. 117:1736–1744. 2011. View Article : Google Scholar : PubMed/NCBI
7	Ambros V: microRNAs: Tiny regulators with great potential. Cell. 107:823–826. 2001. View Article : Google Scholar : PubMed/NCBI
8	Friedman RC, Farh KK, Burge CB and Bartel DP: Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 19:92–105. 2009. View Article : Google Scholar : PubMed/NCBI
9	Lin S and Gregory RI: MicroRNA biogenesis pathways in cancer. Nat Rev Cancer. 15:321–333. 2015. View Article : Google Scholar : PubMed/NCBI
10	Nana-Sinkam SP and Croce CM: Clinical applications for microRNAs in cancer. Clin Pharmacol Ther. 93:98–104. 2013. View Article : Google Scholar : PubMed/NCBI
11	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
12	Burmistrova OA, Goltsov AY, Abramova LI, Kaleda VG, Orlova VA and Rogaev EI: MicroRNA in schizophrenia: Genetic and expression analysis of miR-130b (22q11). Biochemistry (Mosc). 72:578–582. 2007. View Article : Google Scholar : PubMed/NCBI
13	Yip L, Kelly L, Shuai Y, Armstrong MJ, Nikiforov YE, Carty SE and Nikiforova MN: MicroRNA signature distinguishes the degree of aggressiveness of papillary thyroid carcinoma. Ann Surg Oncol. 18:2035–2041. 2011. View Article : Google Scholar : PubMed/NCBI
14	Dong P, Karaayvaz M, Jia N, Kaneuchi M, Hamada J, Watari H, Sudo S, Ju J and Sakuragi N: Mutant p53 gain-of-function induces epithelial-mesenchymal transition through modulation of the miR-130b-ZEB1 axis. Oncogene. 32:3286–3295. 2013. View Article : Google Scholar : PubMed/NCBI
15	Leone V, Langella C, D'Angelo D, Mussnich P, Wierinckx A, Terracciano L, Raverot G, Lachuer J, Rotondi S, Jaffrain-Rea ML, et al: Mir-23b and miR-130b expression is downregulated in pituitary adenomas. Mol Cell Endocrinol. 390:1–7. 2014. View Article : Google Scholar : PubMed/NCBI
16	Sand M, Skrygan M, Sand D, Georgas D, Gambichler T, Hahn SA, Altmeyer P and Bechara FG: Comparative microarray analysis of microRNA expression profiles in primary cutaneous malignant melanoma, cutaneous malignant melanoma metastases, and benign melanocytic nevi. Cell Tissue Res. 351:85–98. 2013. View Article : Google Scholar : PubMed/NCBI
17	Scheffer AR, Holdenrieder S, Kristiansen G, von Ruecker A, Muller SC and Ellinger J: Circulating microRNAs in serum: Novel biomarkers for patients with bladder cancer? World J Urol. 32:353–358. 2014. View Article : Google Scholar : PubMed/NCBI
18	Wu X, Weng L, Li X, Guo C, Pal SK, Jin JM, Li Y, Nelson RA, Mu B, Onami SH, et al: Identification of a 4-microRNA signature for clear cell renal cell carcinoma metastasis and prognosis. PLoS One. 7:e356612012. View Article : Google Scholar : PubMed/NCBI
19	Namlos HM, Meza-Zepeda LA, Baroy 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
20	Kansara M, Teng MW, Smyth MJ and Thomas DM: Translational biology of osteosarcoma. Nat Rev Cancer. 14:722–735. 2014. View Article : Google Scholar : PubMed/NCBI
21	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
22	Iorio MV and Croce CM: MicroRNA dysregulation in cancer: Diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Mol Med. 4:143–159. 2012. View Article : Google Scholar : PubMed/NCBI
23	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
24	Yang C, Cai J, Wang Q, Tang H, Cao J, Wu L and Wang Z: Epigenetic silencing of miR-130b in ovarian cancer promotes the development of multidrug resistance by targeting colony-stimulating factor 1. Gynecol Oncol. 124:325–334. 2012. View Article : Google Scholar : PubMed/NCBI
25	Yu T, Cao R, Li S, Fu M, Ren L, Chen W, Zhu H, Zhan Q and Shi R: MiR-130b plays an oncogenic role by repressing PTEN expression in esophageal squamous cell carcinoma cells. BMC Cancer. 15:292015. View Article : Google Scholar : PubMed/NCBI
26	Lin YH, Wu MH, Liao CJ, Huang YH, Chi HC, Wu SM, Chen CY, Tseng YH, Tsai CY, Chung IH, et al: Repression of microRNA-130b by thyroid hormone enhances cell motility. J Hepatol. 62:1328–1340. 2015. View Article : Google Scholar : PubMed/NCBI
27	Singh B, Carpenter G and Coffey RJ: EGF receptor ligands: Recent advances. F1000Res. 5:pii: F1000. 2016. View Article : Google Scholar
28	Ferguson KM, Berger MB, Mendrola JM, Cho HS, Leahy DJ and Lemmon MA: EGF activates its receptor by removing interactions that autoinhibit ectodomain dimerization. Mol Cell. 11:507–517. 2003. View Article : Google Scholar : PubMed/NCBI
29	Traish AM and Morgentaler A: Epidermal growth factor receptor expression escapes androgen regulation in prostate cancer: A potential molecular switch for tumour growth. Br J Cancer. 101:1949–1956. 2009. View Article : Google Scholar : PubMed/NCBI
30	Gan Y, Shi C, Inge L, Hibner M, Balducci J and Huang Y: Differential roles of ERK and Akt pathways in regulation of EGFR-mediated signaling and motility in prostate cancer cells. Oncogene. 29:4947–4958. 2010. View Article : Google Scholar : PubMed/NCBI
31	Costa RLB, Han HS and Gradishar WJ: Targeting the PI3K/AKT/mTOR pathway in triple-negative breast cancer: A review. Breast Cancer Res Treat. Feb 18–2018.(Epub Ahead of Print). View Article : Google Scholar : PubMed/NCBI
32	Engelman JA: Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer. 9:550–562. 2009. View Article : Google Scholar : PubMed/NCBI
33	Liu P, Cheng H, Roberts TM and Zhao JJ: Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 8:627–644. 2009. View Article : Google Scholar : PubMed/NCBI