Hsa circ 0076931 suppresses malignant biological properties, down-regulates miR-6760-3p through direct binding, and up-regulates CCBE1 in glioma

摘要

The function of circular RNAs (circRNAs) in gliomas is as yet unknown. The present study explored role of hsa circ 0076931 in glioma. circRNA expression profiles were identified via RNA-seq followed by qRT-PCR validation in three pairs of glioma and normal brain tissues (NBT). The function of hsa circ 0076931 was investigated in vitro using cell lines as well as in vivo using a xenograft tumor. Hsa circ 0076931 was up-regulated by overexpression and an mRNA profile compared with wild-type was identified by RNA-seq. The relationship between miR-6760-3p and hsa circ 0076931 or CCBE1 was confirmed via luciferase re-porter or AGO2-RIP assays. A total of 507 circRNAs were identified in glioma tissues that were differentially expressed compared with that in NBT, and the sequencing data were deposited in BioProject (ID: PRJNA746438). Hsa circ 0007694 and hsa circ 0008016 were memorably increased whereas hsa circ 0076931 and hsa circ 0076948 decreased in glioma compared with those in NBT. Additionally, hsa circ 0076931 expression was negatively cor-related with histological grade. Overexpression of hsa circ 0076931 inhibited proliferation, migration, and invasion while promoting apoptosis of glioma cells. A total of 4383 and 537 aberrantly expressed genes were identified between the hsa circ 0076931-overexpressed and control groups in H4 and U118-MG cells, respectively; the sequencing data were de-posited in BioProject (ID: PRJNA746438). These differentially expressed genes were mainly enriched in cancer-related pathways. In addition, elevated hsa circ 0076931 levels induced the expression of CCBE1 while suppressing miR-6760-3p expression. miR-6760-3p can bind to hsa circ 0076931. The experimental evidence supports using hsa circ 0076931 as a marker for glioma and to help prevent malignant progression. The mechanism might be relevant to miR-6760-3p and CCBE1.

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