LncRNA HSP90AA1-IT1 promotes gliomas by targeting miR-885-5p-CDK2 pathway

Oncotarget. 2017 Sep 8;8(43):75284-75297. doi: 10.18632/oncotarget.20777. eCollection 2017 Sep 26.

Abstract

It is well established that ncRNAs are emerging as important regulators in various types of cancers, however, their functions and contributions in cancers remain insufficiently defined. In this study, we reported the expression levels of a long noncoding RNA (lncRNA), named HSP90AA1-IT1 (HSP90AA1 intronic transcript 1), appeared to correlate with the pathological grades of gliomas and high level of HSP90AA1-IT1 indicated poor prognosis. Downregulation of HSP90AA1-IT1 in the glioma cell lines significantly suppressed cell viability, proliferation, EMT, invasion and migration in addition to an increase in apoptosis and aberrant cell cycle progression. The tumorigenic capacity of these cells in vivo were also inhibited. We further demonstrated that the oncogenic effects of HSP90AA1-IT1 could be mediated by a direct binding to miR-885-5p. Sharing the same binding sites with CDK2, a key regulator in gliomagenesis, HSP90AA1-IT1 competitively bound to miR-885-5p, thereby prevented CDK2 from miR-885-5p mediated post-transcriptional repression. Taken together, it is concluded that HSP90AA1-IT1, performs its function via regulating the development of gliomas through miR-885-5p-CDK2 signaling axis, and this has added new perspective to its role in tumorigenesis, thus providing potential therapeutic targets for glioma treatment.

Keywords: CDK2; HSP90AA1-IT1; glioma; lncRNA; miR-885-5p.