Details

Autor(en) / Beteiligte

• Li, Changhui
• Zhang, Shouyun
• Qiu, Tongguo
• Wang, Yuanji
• Ricketts, David M.
• Qi, Chao

Titel

Upregulation of long non-coding RNA NNT-AS1 promotes osteosarcoma progression by inhibiting the tumor suppressive miR-320a

Ist Teil von

• Cancer biology & therapy, 2019-04, Vol.20 (4), p.413-422

Ort / Verlag

United States: Taylor & Francis

Erscheinungsjahr

2019

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• Objective: To investigate the role and mechanism of action of nicotinamide nucleotide transhydrogenase antisense RNA 1 (NNT-AS1) in osteosarcoma (OS). Methods: Bioinformatic analysis suggested miR-320a as potential target of NNT-AS1. Influence of NNT-AS1 overexpression or knockdown on OS cell proliferation, colony-formation, apoptosis, migration and invasion capacity was first investigated. Expression levels of NNT-AS1, miR-320a, beta-catenin, RUNX2, IGF-1R, c-Myc, Cyclin D1 and MMP13 were also evaluated by RT-qPCR and western blotting accordingly. Xenograft models using U2OS and OS-732 cells with different NNT-AS1 gene modifications were constructed for tumor formation assay as well as evaluation of miR-320a, beta-catenin and RUNX2 expression in primary lesion. NNT-AS1-overexpressing U2OS cells and NNT-AS1-knockdown OS-732 cells were subject to miR-320a mimic and inhibitor transfection, respectively, to investigate the miR-320a dependency of the osteosarcoma-promoting role of NNT-AS1. Results: NNT-AS1 overexpression significantly increased proliferation, survival and mobility of U2OS cells in vitro as well as its tumor formation ability in vivo, while NNT-AS1 knockdown showed opposite effect on OS-732 cells. In both in vitro and in vivo model, NNT-AS1 expression level significantly correlated with that of beta-catenin, RUNX2, IGF-1R, c-Myc, Cyclin D1 and MMP13 as well as Akt phosphorylation level, and inversely correlated with miR-320a expression. Transfection of miR-320a mimic significantly inhibiter the promoting effect of NNT-AS1 on cell proliferation, survival and mobility of U2OS cells, while miR-320 inhibitor partially rescued that of OS-732 cells. Conclusion: NNT-As1 functions as a cancer-promoting lncRNA by downregulating miR-320a, thus increasing the protein expression level of beta-catenin, RUNX2 and IGF-1R as well as activation of Akt in osteosarcoma.