LncRNA BCYRN1 inhibits glioma tumorigenesis by competitively binding with miR-619-5p to regulate CUEDC2 expression and the PTEN/AKT/p21 pathway

Abstract

Glioma is the most common malignant tumor in the central nervous system. Altered long noncoding RNAs (lncRNAs) are playing regulatory roles in physiological and pathogenic processes in cancer. Here, we uncovered a differentially expressed lncRNA called brain cytoplasmic RNA 1 (BCYRN1), and elucidated its function and molecular mechanism in the progression and development of glioma. Three fresh tumor tissues from glioma patients and three normal brain tissues from craniocerebral trauma patients were prepared for high-throughput RNA sequencing. Differential RNA transcripts and BCYRN1 were identified by RT-qPCR in glioma samples and controls. CCK-8, colony formation assays, flow cytometry, TUNEL assays, cell migration assays, wound-healing assays, and xenograft model were established to investigate the biological function of BCYRN1 both in vitro and in vivo. Various bioinformatics analysis, dual-luciferase reporter assays, biotinylated RNA pulldown assays, and rescue experiments were conducted to reveal the underlying mechanisms of competitive endogenous RNAs (ceRNAs). 183 lncRNAs were identified with significant dysregulation in glioma and randomly selected differential RNAs were further confirmed by RT-qPCR. Among them, BCYRN1 was the most downregulated lncRNA, and its low expression positively correlated with glioma progression. Functionally, BCYRN1 overexpression inhibited cell proliferation, migration in glioma cell lines, whereas BCYRN1 depletion resulted in the opposite way. MiR-619-5p was further confirmed as the direct target of BCYRN1. Mechanistically, miR-619-5p specifically targeted the CUE domain containing protein 2 (CUEDC2), and BCYRN1/miR-619-5p suppressed glioma tumorigenesis by inactivating PTEN/AKT/p21 pathway in a CUEDC2-dependent manner. Overall, our data presented that the reduced expression of BCYRN1 was associated with poor patient outcome in glioma. BCYRN1 functioned as a ceRNA to inhibit glioma progression by sponging miR-619-5p to regulate CUEDC2 expression and PTEN/AKT/p21 pathway. Our results indicated that BCYRN1 exerted tumor suppressor potential and might be a candidate in the diagnosis and treatment of glioma.

TUC338 Promotes Diffuse Large B Cell Lymphoma Growth via Regulating EGFR/PI3K/AKT Signaling Pathway

“…The ceRNA network is frequently deregulated in human cancer, which is involved in cancer occurrence, development, and progression [ 10 ]. For example, lncRNA BCYRN1 functioned as a tumor suppressor in glioma by sponging miR-619-5p and elevating CUEDC2, thereby inactivating PTEN/AKT/ p 21 pathway [ 11 ]. LncRNA UCA1 was reported as a driver of Warburg effect and carcinogenesis that sponged and inhibited miR-203 activity, leading to increasing HK2 expression in esophageal cancer [ 12 ].…”

Competing Endogenous RNA Networks in Glioma

“… Mu et al (2020) identified 183 lncRNAs that were significantly differentially expressed in the glioma samples of patients compared with normal control and further investigated the function of lncRNA BCYRN1 (brain cytoplasmic RNA 1, also called BC200) which was the most downregulated one. Functionally, they showed that BCYRN1 overexpression can repress the proliferation and migration of glioma cells, while its knockdown has opposite effects.…”

Comprehensive analysis to identify DLEU2L/TAOK1 axis as a prognostic biomarker in hepatocellular carcinoma

“… 30 , 31 , 32 At the same time, some data have indicated that decreased PTEN expression is a common event in HCC and is associated with disease stage, tumor grade and size, and increased expression of tumor markers. 33 , 34 , 35 , 36 …”