LINK‑A lncRNA is upregulated in osteosarcoma and regulates migration, invasion and stemness of osteosarcoma cells

Kong,Yao; Nie,Zhikui; Guo,Hongmin; Ma,Cao

doi:10.3892/ol.2020.11367

LINK‑A lncRNA is upregulated in osteosarcoma and regulates migration, invasion and stemness of osteosarcoma cells

Authors:
- Yao Kong
- Zhikui Nie
- Hongmin Guo
- Cao Ma
View Affiliations

Affiliations: Department of Osteoarthrosurgery, Jining First People's Hospital, Jining, Shandong 272100, P.R. China
Published online on: February 5, 2020 https://doi.org/10.3892/ol.2020.11367
Pages: 2832-2838
Copyright: © Kong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The present study aimed to investigate the involvement of long intergenic non‑coding RNA for kinase activation (LINK‑A) long non‑coding RNA (lncRNA) in osteosarcoma. Plasma levels of LINK‑A lncRNA and transforming growth factor β1 (TGF‑β1) were measured by reverse transcription‑quantitative polymerase chain reaction and ELISA, respectively. Correlation between LINK‑A lncRNA and TGF‑β1 was analyzed by Pearson correlation coefficient. LINK‑A lncRNA and TGF‑β1 were upregulated in patients with osteosarcoma compared with healthy controls. LINK‑A lncRNA and TGF‑β1 were positively correlated in the two groups. LINK‑A lncRNA short hairpin RNAs (shRNAs) were transfected into osteosarcoma cell lines and Transwell migration assay, Matrigel invasion assay and flow cytometry were used to evaluate cell migration, invasion and stemness, respectively. Effects of LINK‑A lncRNA silencing and overexpression on TGF‑β1 expression were analyzed by western blotting. LINK‑A lncRNA shRNA silencing inhibited, whereas TGF‑β1 treatment promoted cell migration, invasion and stemness. LINK‑A lncRNA silencing inhibited TGF‑β1 expression, whereas TGF‑β1 treatment had no effects on LINK‑A lncRNA expression. TGF‑β1 reduced the inhibitory effects of LINK‑A lncRNA knockdown on cancer cell migration, invasion and stemness. These data indicated that LINK‑A lncRNA is upregulated in osteosarcoma and may regulate migration, invasion and stemness of osteosarcoma cells through TGF‑β1.

View Figures

View References

1	Moreno F, Cacciavillano W, Cipolla M, Coirini M, Streitenberger P, López Martí J, Palladino M, Morici M, Onoratelli M, Drago G, et al: Childhood osteosarcoma: Incidence and survival in Argentina. Report from the national pediatric cancer registry, ROHA network 2000–2013. Pediatr Blood Cancer. 64:2017. View Article : Google Scholar
2	Durfee RA, Mohammed M and Luu HH: Review of osteosarcoma and current management. Rheumatol Ther. 3:221–243. 2016. View Article : Google Scholar : PubMed/NCBI
3	Anderson ME: Update on survival in osteosarcoma. Orthop Clin North Am. 47:283–292. 2016. View Article : Google Scholar : PubMed/NCBI
4	Berner K, Johannesen TB, Berner A, Haugland HK, Bjerkehagen B, Bøhler PJ and Bruland ØS: Time-trends on incidence and survival in a nationwide and unselected cohort of patients with skeletal osteosarcoma. Acta Oncol. 54:25–33. 2015. View Article : Google Scholar : PubMed/NCBI
5	Slade AD, Warneke CL, Hughes DP, Lally PA, Lally KP, Hayes-Jordan AA and Austin MT: Effect of concurrent metastatic disease on survival in children and adolescents undergoing lung resection for metastatic osteosarcoma. J Pediatr Surg. 50:157–160. 2015. View Article : Google Scholar : PubMed/NCBI
6	Nakao A, Afrakhte M, Morén A, Nakayama T, Christian JL, Heuchel R, Itoh S, Kawabata M, Heldin NE, Heldin CH and ten Dijke P: Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling. Nature. 389:631–635. 1997. View Article : Google Scholar : PubMed/NCBI
7	Soderberg SS, Karlsson G and Karlsson S: Complex and context dependent regulation of hematopoiesis by TGF-beta superfamily signaling. Ann N Y Acad Sci. 1176:55–69. 2009. View Article : Google Scholar : PubMed/NCBI
8	Akhurst RJ and Derynck R: TGF-beta signaling in cancer-a double-edged sword. Trends Cell Biol. 11:S44–S51. 2001. View Article : Google Scholar : PubMed/NCBI
9	Willis BC and Borok Z: TGF-beta-induced EMT: Mechanisms and implications for fibrotic lung disease. Am J Physiol Lung Cell Mol Physiol. 293:L525–L534. 2007. View Article : Google Scholar : PubMed/NCBI
10	Mondal T, Subhash S, Vaid R, Enroth S, Uday S, Reinius B, Mitra S, Mohammed A, James AR, Hoberg E, et al: MEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA-DNA triplex structures. Nat Commun. 6:77432015. View Article : Google Scholar : PubMed/NCBI
11	Li Z, Dong M, Fan D, Hou P, Li H, Liu L, Lin C, Liu J, Su L, Wu L, et al: lncRNA ANCR down-regulation promotes TGF-β-induced EMT and metastasis in breast cancer. Oncotarget. 8:67329–67343. 2017.PubMed/NCBI
12	Lin A, Li C, Xing Z, Hu Q, Liang K, Han L, Wang C, Hawke DH, Wang S, Zhang Y, et al: The LINK-A lncRNA activates normoxic HIF1α signalling in triple-negative breast cancer. Nat Cell Biol. 18:213–224. 2016. View Article : Google Scholar : PubMed/NCBI
13	Ma J and Xue M: LINK-A lncRNA promotes migration and invasion of ovarian carcinoma cells by activating TGF-β pathway. Biosci Rep. 38(pii): BSR201809362018. View Article : Google Scholar : PubMed/NCBI
14	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
15	Atiye J, Wolf M, Kaur S, Monni O, Böhling T, Kivioja A, Tas E, Serra M, Tarkkanen M and Knuutila S: Gene amplifications in osteosarcoma-CGH microarray analysis. Genes Chromosomes Cancer. 42:158–163. 2005. View Article : Google Scholar : PubMed/NCBI
16	Li JP, Liu LH, Li J, Chen Y, Jiang XW, Ouyang YR, Liu YQ, Zhong H, Li H and Xiao T: Microarray expression profile of long noncoding RNAs in human osteosarcoma. Biochem Biophys Res Commun. 433:200–206. 2013. View Article : Google Scholar : PubMed/NCBI
17	Solar M and Paul W: Chain relaxation in thin polymer films: Turning a dielectric type-B polymer into a type-A' one. Soft Matter. 13:1646–1653. 2017. View Article : Google Scholar : PubMed/NCBI
18	Hawinkels LJ, Paauwe M, Verspaget HW, Wiercinska E, van der Zon JM, van der Ploeg K, Koelink PJ, Lindeman JH, Mesker W, ten Dijke P and Sier CF: Interaction with colon cancer cells hyperactivates TGF-β signaling in cancer-associated fibroblasts. Oncogene. 33:97–107. 2014. View Article : Google Scholar : PubMed/NCBI
19	Colak S and Ten Dijke P: Targeting TGF-β signaling in cancer. Trends Cancer. 3:56–71. 2017. View Article : Google Scholar : PubMed/NCBI