The Role of CASC2 and miR-21 Interplay in Glioma Malignancy and Patient Outcome.

Daina Skiriute,Giedrius Steponaitis,Arimantas Tamasauskas,Paulina Vaitkiene,Rytis Stakaitis

doi:10.3390/ijms21217962

Abstract

Recently long non-coding RNAs (lncRNAs) were highlighted for their regulatory role in tumor biology. The novel human lncRNA cancer susceptibility candidate 2 (CASC2) has been characterized as a potential tumor suppressor in several tumor types. However, the roles of CASC2 and its interplay with miR-21 in different malignancy grade patient gliomas remain unexplored. Here we screened 99 different malignancy grade astrocytomas for CASC2, and miR-21 gene expression by real-time quantitative polymerase chain reaction (RT-qPCR) in isocitrate dehydrogenase 1 (IDH1) and O-6-methylguanine methyltransferase (MGMT) assessed gliomas. CASC2 expression was significantly downregulated in glioblastomas (p = 0.0003). Gliomas with low CASC2 expression exhibited a high level of miR-21, which was highly associated with the higher glioma grade (p = 0.0001), IDH1 wild type gliomas (p < 0.0001), and poor patient survival (p < 0.001). Taken together, these observations suggest that CASC2 acts as a tumor suppressor and potentially as a competing endogenous RNA (ceRNA) for miR-21, plays important role in IDH1 wild type glioma pathogenesis and patients’ outcomes.

Highlights

Malignant gliomas, especially glioblastomas, are highly infiltrative, rapidly growing, aggressive, heterogeneous, chemo-resistant, and lethal neoplasms [1]
Current knowledge on the involvement and function of Long non-coding RNAs (lncRNAs) cancer susceptibility candidate 2 (CASC2) in glioma evidences the availability of a small amount of data from clinical samples
In agreement with our data, CASC2 expression in both studies was shown to correlate with glioma malignancy grade inversely

Summary

Introduction

Especially glioblastomas, are highly infiltrative, rapidly growing, aggressive, heterogeneous, chemo-resistant, and lethal neoplasms [1]. Long non-coding RNAs (lncRNAs) were first recognized as being crucial regulators of gene expression in a wide range of biological context, including cancer [3]. Various lncRNAs, including homeobox (HOX) transcript antisense RNA (HOTAIR), metastasis associated lung adenocarcinoma transcript (MALAT), colorectal neoplasia differentially expressed (CRNDE), have been identified as novel players in glioma pathogenesis demonstrating associations with tumor subtype, histological stage, tumor isocitrate dehydrogenase (IDH) mutational status, chemosensitivity, and patient survival [4,5,6,7,8]. Growing evidence on the ability of lncRNAs to interact with DNA, RNA, and proteins acting as tethers, guides, decoys, and scaffolds, includes them in the posttranscriptional regulatory network in cancer biology [9]. A large number of lncRNAs act as a competing endogenous RNAs (ceRNA) or sponges for microRNAs, for example, phosphatase and tensin homolog pseudogene

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