Long intergenic non-protein coding RNA 00475 silencing acts as a tumor suppressor in glioma under hypoxic condition by impairing microRNA-449b-5p-dependent AGAP2 up-regulation

Abstract

Objective: Long non-coding RNAs have been demonstrated to be involved in the progression of a variety of cancers, including glioma. Through microarray analyses, long intergenic non-protein coding RNA 00475 (LINC00475) was identified in the glioma development. However, its potential role remains incompletely understood. This study aimed to elucidate the effect of LINC00475 on the development of glioma under hypoxic conditions. Methods: Glioma cells underwent hypoxic treatment and were collected. The functional role of LINC00475 and AGAP2 in glioma was determined using ectopic expression, depletion, and reporter assay experiments. Then, the expression of LINC00475, microRNA (miR)-449b-5p, AGAP2, FAK, and HIF-1α was determined. In addition, cell migration and invasion were examined. Finally, a tumor xenograft was carried out in nude mice to explore the role of LINC00475 on oxidation in vivo. Results: LINC00475 was identified to be overexpressed in hypoxic glioma samples, which was further observed to bind to and down-regulate miR-449b-5p, and negatively targeted AGAP2. Moreover, we also revealed a positive correlation between LINC00475 and AGAP2 expression in glioma. In addition, silencing of LINC00475 decreased the extent of FAK phosphorylation and reduced the expression of HIF-1α and AGAP2. It was also observed that LINC00475 silencing suppressed glioma cell proliferation, migration, and invasion, and promoted cell apoptosis. Moreover, oxidation of nude mice was promoted by LINC00475 silencing. Conclusion: Taken together, LINC00475 silencing exerted an inhibitory effect on glioma under hypoxic conditions by down-regulating AGAP2 via up-regulation of miR-449b-5p.

Prediction of a Potential Mechanism of Intervertebral Disc Degeneration Based on a Novel Competitive Endogenous RNA Network

“…Wang et al verified the contribution of miR-5100 to osteoblast differentiation and mineralization through functional gain and loss experiments, but there is still a lack of studies on miR-5100 in hypertrophic chondrocytes, type X collagen, or IDD. For lncRNA that may negatively regulate miR-5100, the current studies of LINC00475, Sox2-OT, SNHG12, AGAP2-AS1, and TARID are focused on various types of tumours, such as glioma, lymphoma, ovarian cancer, and renal clear cell sarcoma [52][53][54][55], while Wang et al sug-gested that the overexpression of lncRNA GAS5 might promote the apoptosis of NPC through downregulation of Bcl-2 and upregulation of caspase-3 [56]. It is worth noting that NEAT1 may be the ceRNA-regulating COL10A1.…”

Roles of Long Noncoding RNAs in Conferring Glioma Progression and Treatment

“…SNHG1 regulated the miRNA154-5p/miR-376b-3p-FOXP2-KDM5B positive feedback loop to promote the malignant phenotype of glioma cells (43). LINC00475 silencing acted as a tumor suppressor in glioma under hypoxic conditions by impairing miRNA-449b-5p-dependent upregulation of AGAP2 expression (44). TRPM2-AS inhibited the growth, migration, and invasion of gliomas through JNK, c-Jun, and RGS4 (45).…”

The Hypoxia–Long Noncoding RNA Interaction in Solid Cancers

“…In glioblastoma, it was identified that miR-449b-5p targets phosphatidylinositol 3-kinase enhancer ( PIKE , also known as ArfGAP with GTPase domain, ankyrin repeat and PH domain 2 ( AGAP2 )) [ 63 ], which possesses an anti-apoptotic activity [ 78 , 79 ]. LINC00475 can upregulate PIKE by impeding miR-449b-5p activities.…”

“…LINC00475 can upregulate PIKE by impeding miR-449b-5p activities. The knockdown of LINC00475 induces apoptotic cell death in vitro and restricts the growth of glioblastoma in vivo [ 63 ] ( Figure 1 and Table 1 ). Accumulating evidence reveals that miR-449b-5p serves as a tumor suppressor by suppressing various cellular factors, such as yin and yang 1 ( YY1 ), cell-cycle related and expression-elevated protein in tumor ( CREPT ), and Wnt family member 2B ( WNT2B ) [ 80 , 81 , 82 ].…”