Hsa_circ_0076931 suppresses malignant biological properties, down-regulates miR-6760-3p through direct binding, and up-regulates CCBE1 in glioma.

Abstract

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 reporter 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 correlated 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 deposited 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.

• Authors: Yanbin Ke, Shixing Su, Chuanzhi Duan, Yezhong Wang, Guobin Cao, Zelu Fang, Yonghua Tuo, Wei Li, Zhaotao Wang, Shizhen Zhang
• Journal: Bioscience reports (Biosci Rep) Vol. 42 Issue 1 (01 28 2022) ISSN: 1573-4935 [Electronic] England
• PMID: 34931668 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 The Author(s).

Chemical References

• CCBE1 protein, human
• Calcium-Binding Proteins
• MIRN6760 microRNA, human
• MicroRNAs
• RNA, Circular
• Tumor Suppressor Proteins

Topics

• Adult
• Animals
• Apoptosis
• Brain Neoplasms (genetics, metabolism, pathology)
• Calcium-Binding Proteins (genetics, metabolism)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Female
• Gene Expression Regulation, Neoplastic
• Glioma (genetics, metabolism, pathology)
• Humans
• Male
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• Middle Aged
• Neoplasm Invasiveness
• RNA, Circular (genetics, metabolism)
• Signal Transduction
• Transcriptome
• Tumor Burden
• Tumor Suppressor Proteins (genetics, metabolism)
• Up-Regulation