Background:
Glioblastoma (GB) is one of the most common (~30%) and lethal
cancers of the central nervous system. Although new
therapies are emerging, chemoresistance to treatment is one of the major challenges in
cancer treatment. Brain cytoplasmic 200 (BC200)
RNA, also known as BCYRN1, is a
long noncoding RNA (
lncRNA) that has recently emerged as one of the crucial members of the
lncRNA family. BC200 atypical expression is observed in many human
cancers. BC200 expression is higher in invasive
cancers than in benign
tumors. However, the clinical significance of BC200 and its effect on GB multiforme is still unexplored and remains unclear. Methods: BC200 expression in GB patients and cell lines were investigated through RT-qPCR, immunoblotting, and immunohistochemistry analysis. The biological importance of BC200 was investigated in vitro and in vivo through knockdown and overexpression. Bioinformatic analysis was performed to determine
miRNAs associated with BC200
RNA. Results: Our findings revealed that in GB patients, BC200
RNA expression was higher in blood and
tumor tissues than in normal tissues. BC200
RNA expression have a statistically significant difference between the IDH1 and P53 status. Moreover, the BC200
RNA expression was higher than both p53, a prognostic marker of
glioma, and Ki-67, a reliable
indicator of
tumor cell proliferation activity. Overexpression and silencing of BC200
RNA both in vitro and in vivo significantly modulated the proliferation, self-renewal, pluripotency, and
temozolomide (TMZ) chemo-resistance of GB cells. It was found that the expressions of BC200 were up-regulated and that of miR-218-5p were down-regulated in GB tissues and cells. miR-218-5p inhibited the expression of BC200. Conclusions: This study is the first to show that the molecular mechanism of BC200 promotes GB oncogenicity and TMZ resistance through miR-218-5p expression modulation. Thus, the
noncoding RNA BC200/miR-218-5p signaling circuit is a potential clinical
biomarker or therapeutic target for GB.