Long non-coding RNA ANRIL is associated with a poor prognosis of osteosarcoma and promotes tumorigenesis via PI3K/Akt pathway

J Bone Oncol. 2018 Feb 13:11:51-55. doi: 10.1016/j.jbo.2018.02.002. eCollection 2018 Jun.

Abstract

Aim: Increasing evidence has shown that long noncoding RNAs (lncRNAs) ANRIL may function as oncogenes in various types of malignancies. However, there is still a lack of knowledge concerning its role in osteosarcoma (OS). In this study, we aimed to investigate the influence of ANRIL on cell proliferation and invasion of OS and to determine its association with clinicopathological features of the patients.

Methods: The tumor specimens and the adjacent normal tissues were collected from 57 OS patients and the expression level of ANRIL was quantified by RT-qPCR. High expression of ANRIL was defined as a relative mRNA expression of > 1.5 fold (tumor/normal). Knockdown of ANRIL was performed in human OS cell lines to investigate its influence on cell proliferation, apoptosis and invasion. In addition, expression of downstream genes in the transfected cells were determined by Western blot.

Results: The expression level of ANRIL was significantly increased in OS tissues than in the adjacent normal tissues. 33 patients were included in the high expression group and the other 24 patients were included in the normal expression group. ANRIL expression was significantly associated with tumor size (5.7 cm ± 2.4 cm vs. 4.3 cm ± 1.7 cm, p = 0.02) and the 5-year survival rate (51.5% vs. 79.1%, p = 0.03). Knockdown of ANRIL could significantly induce cell apoptosis and inhibit cell proliferation and invasion. Moreover, knockdown of ANRIL could significantly decrease the expression level of phosphorylated PI3K and AKT in OS cells.

Conclusions: Upregulated expression of ANRIL is associated with the tumor development and prognosis of OS. ANRIL may regulate the function of OS cells through the AKT pathway.

Keywords: AKT; ANRIL; Long noncoding RNA; Osteosarcoma.