Integrative transcriptome analysis identified a BMP signaling pathway-regulated lncRNA AC068643.1 in IDH mutant and wild-type glioblastomas

Abstract

Glioblastomas (GBMs) are classified into isocitrate dehydrogenase (IDH) mutant (IDHMT) and wild-type (IDHWT) subtypes, and each is associated with distinct tumor behavior and prognosis. The present study aimed to investigate differentially expressed long non-coding (lnc)RNAs and mRNAs between IDHMT and IDHWT GBMs, as well as to explore the interaction and potential functions of these RNAs. A total of 132 GBM samples with RNA profiling data (10 IDHMT and 122 IDHWT cases) were obtained from The Cancer Genome Atlas, and 62/78 and 142/219 up/downregulated lncRNAs and mRNAs between IDHMT and IDHWT GBMs were identified, respectively. Multivariate Cox analysis of the dysregulated lncRNAs/mRNAs identified three-lncRNA and fifteen-mRNA signatures with independent prognostic value, indicating that these RNAs may serve roles in determining distinct tumor behaviors and prognosis of patients with IDHMT/WT GBMs. Functional analysis of the three lncRNAs revealed that they were primarily associated with cell stemness or differentiation. Pearson's correlation analysis revealed that the protective lncRNA AC068643.1 was significantly positively correlated with two key bone morphogenetic protein (BMP) signaling-associated mRNAs, Bone morphogenetic protein 2 (BMP2) and Myostatin (MSTN), from the 15 mRNAs. Further in vitro studies demonstrated that BMP2 and MSTN directly stimulated AC068643.1 expression. In conclusion, the present study identified a BMP signaling pathway-regulated lncRNA AC068643.1, which may contribute to the different tumor behaviors observed between IDHMT and IDHWTGBMs.