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

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.

Identification of circRNA-miRNA-mRNA network in luminal breast cancers by integrated analysis of microarray datasets

“…Growing evidence has validated the ceRNA function of circRNAs in cancers (Becatti et al, 2023). For instance, circularLRRC7 can exert as a potential glioblastoma suppressor by functioning as ceRNA for miR-1281 (Kong et al, 2021). In the current study, microarray datasets from the GEO database were downloaded and analyzed to identify robust differentially expressed circRNAs, miRNAs, and mRNAs that are specific to luminalsubtype breast cancer.…”

Underlying mechanisms and clinical potential of circRNAs in glioblastoma

“…Hsa_circ_0114014 (circLRRC7) is an ecRNA produced from the LRRC7 gene [ 113 ]. Low circLRRC7 expression in GBM tissues was revealed to indicate poor prognosis.…”

“…CircLRRC7 could repress GBM development. Analysis showed that miR-1281 might be a downstream target of circLRRC7 and that PDXP, a protein that participates in tumor metabolism [ 114 ], was the direct target of miR-1281 [ 113 ]. A high level of PDXP suggested a long overall survival time in GBM patients [ 113 ].…”

“…Analysis showed that miR-1281 might be a downstream target of circLRRC7 and that PDXP, a protein that participates in tumor metabolism [ 114 ], was the direct target of miR-1281 [ 113 ]. A high level of PDXP suggested a long overall survival time in GBM patients [ 113 ]. In summary, circLRRC7 might act as a tumor suppressor in GBM by regulating the miR-1282-PDXP pathway.…”

Advantages of Noncoding RNAs in Molecular Diagnosis

“…Although there are differences in miRNA expression profiles between normal and tumor tissues, many of these miRNAs are only indirectly altered by genetic changes that occur during carcinogenesis, epigenomic dynamics, and physiological changes in cell biology and do not directly trigger tumor development. Differentially expressed miRNAs between tumor and normal tissues have been identified in lymphomas, breast cancer, lung cancer, papillary thyroid cancer, glioblastoma, hepatocellular carcinoma, pancreatic tumor, pituitary adenoma, cervical cancer, brain tumors, prostate cancer (PCa), kidney and bladder cancer, and colon cancer [63][64][65][66][67][68][69][70][71][72][73][74][75][76]. The involvement of miRNAs in the carcinogenic process may involve changes in the components of Predicted binding sites for miRNAs in genes.…”