LINC00467 facilitates the proliferation, migration and invasion of glioma via promoting the expression of inositol hexakisphosphate kinase 2 by binding to miR-339-3p.

Our previous studies indicate that long noncoding RNA (lncRNA) LINC00467 can act as an oncogene to participate in the malignant progression of glioma, but the underlying molecular mechanism remains to be studied further. This study aimed to explore the biological role of the LINC00467/miR-339-3p/ inositol hexakisphosphate kinase 2 (IP6K2) regulatory axis in glioma. The Cancer Genome Atlas (TCGA), Oncomine databases and reverse transcription­quantitative PCR (RT­qPCR) were used to analyze IP6K2 expression in glioma. RT-PCR, EdU and transwell assays were conducted to observe the effect of IP6K2 on glioma cell proliferation, migration and invasion. Using bioinformatics analysis, RT-PCR, and dual luciferase reporter gene assay, the potential role of the LINC00467/miR-339-3p/IP6K2 regulatory axis in glioma was verified. The results showed that IP6K2 was up-regulated in glioma tissues and cell lines. Moreover, the expression level of IP6K2 was correlated with the clinical features of glioma patients. In vitro and in vivo experiments indicated that IP6K2 overexpression could promote the proliferation, migration, and invasion of glioma cells. Further bioinformatics analysis and in vitro assays revealed that LINC00467 could promote IP6K2 expression by binding to miR-339-3p and promote the malignant progression of glioma. Overall, LINC00467 could upregulate IP6K2 by binding to miR-339-3p and promote the proliferation, migration, and invasion of glioma cells. The LINC00467/miR-339-3p/IP6K2 regulatory axis might be a potential therapeutic target for glioma.

Long Noncoding RNA LINC00467 Promotes Glioma Progression through Inhibiting P53 Expression via Binding to DNMT1.

Purpose: This study aimed to investigate whether long noncoding RNA (lncRNA) LINC00467 could regulate proliferative and invasive abilities of glioma cells via p53 and DNA methyltransferase 1 (DNMT1), so as to participate in the occurrence and progression of glioma. Methods: LINC00467 expression in glioma was analyzed by GEPIA database and LINC00467 expression in glioma cell lines was detected by qRT-PCR. The regulatory effects of LINC00467 and p53 on proliferative, invasive capacities and cell cycle were conducted by CCK-8 and EdU assays, transwell assay and flow cytometry, respectively. The binding conditions between LINC00467, DNMT1 and p53 were determined by RNA immunoprecipitation (RIP) and Chromatin immunoprecipitation (ChIP) assays. Western blot was conducted to determine whether LINC00467 could regulate p53 in glioma cells. Finally, rescue experiments were carried out to evaluate whether LINC00467 regulates proliferative and invasive abilities of glioma cells through p53. Results: The expression of LINC00467 was significantly up-regulated in tumor samples than that in normal samples, which was not correlated with patient survival time. Besides, expression of LINC00467 was higher in glioma cells than that of negative control cells. Upregulation of LINC00467 promoted proliferative and invasive abilities, and accelerated cell cycle in G0/G1 phase of U87 and LN229 cells. The results of RIP and ChIP assays demonstrated that LINC00467 could bind to DNMT1 and inhibit p53 expression. Overexpression of p53 partially reversed the enhancement of LINC00467 on proliferative and invasive abilities of glioma cells. Conclusion: These results indicated that high expression of LINC00467 could promote proliferative and invasive abilities of glioma cells through targeting inhibition of p53 expression by binding to DNMT1.

Circular RNA HIPK3 promotes glioma progression by binding to miR-124-3p.

This study aims to investigate whether circ-HIPK3 could promote the proliferation and invasion of glioma cells by upregulating STAT3 after binding to miR-124-3p, thus participating in the development of glioma. Expression levels of circ-HIPK3, miR-124-3p and STAT3 in glioma cell lines were determined using qRT-PCR. The regulatory effects of circ-HIPK3, miR-124-3p and STAT3 on proliferative and invasive capacities of glioma cells were accessed using EdU assay, CCK-8 assay and invasion assay, respectively. Cell cycle assay and cell apoptosis assay were performed by flow cytometry. Dual-luciferase reporter gene assay was conducted to determine the binding condition among circ-HIPK3, miR-124-3p and STAT3. Rescue experiments were performed in co-transfected glioma cells. QRT-PCR data showed that circ-HIPK3 and STAT3 are highly expressed, whereas miR-124-3p is lowly expressed in glioma cells than those of negative control cell. Knockdown of circ-HIPK3 in U87 and U251 cells inhibited their proliferative and invasive capacities. On the contrary, miR-124-3p knockdown improved proliferative and migratory capacities. Dual-luciferase reporter gene assay exerted that circ-HIPK3 could bind to miR-124-3p and STAT3 is the target gene of miR-124-3p. Western blot results elucidated that circ-HIPK3 stabilizes STAT3 expression, whereas miR-124-3p degrades STAT3 expression. Rescue experiments demonstrated that overexpression of circ-HIPK3 could partially reverse the inhibited proliferative and migratory capacities induced by miR-124-3p in U87 and U251 cells. In summary, we found that overexpression of circ-HIPK3 promotes proliferative and invasive capacities of glioma cells by sponging miR-124-3p to upregulate STAT3 expression.