CircularLRRC7 is a Potential Tumor Suppressor Associated With miR-1281 and PDXP Expression in Glioblastoma

Xue Kong; Ruiting Xu; Wei Wang; Minghui Zeng; Yuan Li; Mengyu Lin; Wenchao Zhou; Xianming Fu; Haibo Wu

doi:10.3389/fmolb.2021.743417

CircularLRRC7 is a Potential Tumor Suppressor Associated With miR-1281 and PDXP Expression in Glioblastoma

Front Mol Biosci. 2021 Nov 29:8:743417. doi: 10.3389/fmolb.2021.743417. eCollection 2021.

Authors

Xue Kong^{1

2

3

4}, Ruiting Xu⁴, Wei Wang^{3

4}, Minghui Zeng⁵, Yuan Li⁴, Mengyu Lin⁴, Wenchao Zhou⁴, Xianming Fu^{1

2

5}, Haibo Wu^{3

4}

Affiliations

¹ School of Medicine, Shandong University, Jinan, China.
² Department of Neurosurgery, Anhui Provincial Hospital, Shandong University, Hefei, China.
³ Department of Pathology, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China.
⁴ Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, Intelligent Pathology Institute, University of Science and Technology of China, Hefei, China.
⁵ Department of Neurosurgery, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China.

Abstract

Circular RNAs (circRNAs) are usually enriched in neural tissues, yet about 80% circRNAs have lower expression in gliomas relative to normal brains, highlighting the importance of circRNAs as tumor suppressors. However, the clinical impact as well as the pathways regulated by the tumor-suppressive circRNAs remain largely unknown in glioblastoma (GBM). Through bioinformatic analysis followed by experimental validation, we found that hsa_circ_0114014 (circLRRC7) was dramatically down-regulated in GBM when compared with normal brain tissues (p < 0.0001). GBM patients with a lower circLRRC7 expression had poorer progression-free survival (PFS, p < 0.05) and overall survival (OS, p < 0.05). Analyses of the predicted target miRNAs of circLRRC7 in CSCD and CRI databases, in combination with the miRNA expression data in GBMs and normal brains from GSE database, revealed miR-1281 as a potential downstream target of circLRRC7. Subsequently, the target genes of hsa-mir-1281 were predicted by TargetScan, miRDB and miRNATAR databases. Intersection analysis and correlation test indicated that PDXP was a potential target of miR-1281. In summary, circLRRC7 may be a tumor suppressor that associated with miR-1281 and PDXP expression in GBM, which may provide novel therapeutic targets for GBM treatment.

Keywords: GBM; PDXP; circRNA; hsa_circ-0114014; miR-1281; miRNA; tumor suppressor.