MicroRNA-524 inhibits the progress of glioma via the direct targeting of NCF2.
Tuoye XuWan YuQingquan LiXiaojian LiYan ShiBoqiang CaoYaxuan ZhangSeng WangYan ZhangTianlu WangBaosheng Huang
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Abstract:
In recent years, a large amount of research has reported that microRNA (miRNA) dysregulation is closely related to glioma progression. miR-524, a member of the miRNA family, has been confirmed to be involved in many human diseases, including glioma. However, the role and molecular mechanism of miR-524 in glioma have not been clarified. In our study, we showed that miR-524 expression was significantly decreased in glioma and was associated with glioma recurrence. Next, we performed a series of assays and confirmed that the upregulation of miR-524 suppressed glucose uptake, proliferation, migration and invasion in glioma cell lines. Then, through bioinformatics software and a dual luciferase assay, we demonstrated that NCF2 was a target gene of miR-524. In addition, we found that NCF2 reintroduction restored the inhibitor effect of miR-524 on glioma progression. These results elucidate the mechanism of miR-524 in glioma development and provide a potential therapeutic strategy for glioma patients.Cite
Glioma is the most common and lethal malignant intracranial tumor. Long noncoding RNAs (lncRNAs) have been identified as pivotal regulators in the tumorigenesis of glioma. However, the role of lncRNA urothelial carcinoma-associated 1 (UCA1) in glioma genesis is still unknown. The purpose of this study was to investigate the underlying function of UCA1 on glioma genesis. The results demonstrated that UCA1 was upregulated in glioma tissue and indicated a poor prognosis. UCA1 knockdown induced by si-UCA1 significantly suppressed the proliferative, migrative, and invasive activities of glioma cell lines (U87 and U251). Bioinformatics analysis and luciferase reporter assay verified the complementary binding within UCA1 and miR-122 at the 3′-UTR. Functional experiments revealed that UCA1 acted as an miR-122 “sponge” to modulate glioma cell proliferation, migration, and invasion via downregulation of miR-122. Overall, the present study demonstrated that lncRNA UCA1 acts as an endogenous sponge of miR-122 to promote glioma cell proliferation, migration, and invasion, which provides a novel insight and therapeutic target in the tumorigenesis of glioma. An erratum for this article has been published in Oncology Research, Volume 28, Number 6, pp.683-684 (https://www.ingentaconnect.com/contentone/cog/or/2021/00000028/00000006/art00011). Note that an updated article PDF will be delivered from this page further to the issuing of the erratum.
Competing Endogenous RNA
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U87
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Brain tumor
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Glioma is a highly heterogeneous and lethal tumor with an extremely poor prognosis. Through analysis of TCGA data, we identified that OLFML2A is a key promotor of gliomagenesis. However, the molecular function of OLFML2A and its underlying mechanism of action in glioma remain unclear. In this study, we found that OLFML2A expression was significantly upregulated in glioma specimens and positively correlated with pathological grades in glioma patients. Moreover, Kaplan-Meier survival analysis of TCGA data revealed that glioma patients with higher OLFML2A expression had shorter overall survival. Importantly, OLFML2A knockdown in glioma cells inhibited cell proliferation and promoted apoptosis. Mechanistically, OLFML2A downregulation inhibits Wnt/β-catenin signaling by upregulating amyloid precursor protein (APP) expression and reducing stabilized β-catenin levels, leading to the repression of MYC, CD44, and CSKN2A2 expression. Furthermore, OLFML2A downregulation suppressed the growth of transplanted glioma subcutaneously and intracranially by inhibiting Wnt/β-catenin pathway-dependent cell proliferation. By uncovering the oncogenic effects in human and rodent gliomas, our data support OLFML2A as a potential therapeutic target for glioma.
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Glioma is the common highly malignant primary brain tumor. However, the molecular pathways that result in the pathogenesis of glioma remain elusive. In this study, we found that microRNA-103 (miR-103), microRNA-195 (miR-195), or microRNA-15b (miR-15b), which all have the same 5' "seed" miRNA portion and share common binding sites in the SALL4 3'-untranslated region (UTR), were downregulated in glioma tissues and cell lines. These miRNAs suppressed glioma cell proliferation, migration, and invasion, induced cell apoptosis, and decreased the level of the SALL4 protein, but not that of SALL4 mRNA, which was identified as a direct target of all three miRNAs. The caspase-3/7 activity expression in U251 cells overexpressing these miRNAs was rescued during SALL4 upregulation. An obvious inverse correlation was observed between SALL4 and miR-103 or miR-195 expression levels in clinical glioma samples. Moreover, enforced expression of SALL4 stimulated cell proliferation, migration, and invasion. In conclusion, these data suggest that miR-103, miR-195, and miR-15b post-transcriptionally downregulated the expression of SALL4 and suppressed glioma cell growth, migration, and invasion, and increased cell apoptosis. These results provide a potential therapeutic target that may downregulate SALL4 in glioma.
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Malignant gliomas are the most common and deadly primary brain tumors in adults. Increasing evidence has indicated that microRNAs (miRNAs) have an influence on the regulation of apoptotic cell signaling. Downregulation of miRNA 218 (miR-218) has been indicated in human glioma specimens. Here, we investigate the function of miR-218 in apoptosis and tumor growth of glioma cells. The expression of miR-218 was detected by real-time quantitative reverse transcriptase PCR. The effects of miR-218 on glioma cell proliferation and tumorigenicity were investigated by in vitro clonogenicity and in vivo xenograft assay. Apoptosis was evaluated by flow cytometric analysis and assay by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling. The downstream targets of miR-218 were identified by bioinformatics analysis and further validated by Western blot and luciferase reporter assay. Overexpression of miR-218 induces glioma cell apoptosis and inhibits glioma cell viability, proliferation, and tumorigenicity. Epidermal growth factor receptor–coamplified and overexpressed protein (ECOP) was identified as a functional downstream target of miR-218, which can regulate transcriptional activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and associated with apoptotic response. Ectopic expression of ECOP rescued the glioma cells from miR-218–induced apoptosis and increased NF-κB activity. These results suggest that miR-218 sensitizes glioma cells to apoptosis by regulating ECOP-mediated suppression of NF-κB activity, which may provide novel opportunities for glioma therapy.
Ectopic expression
Viability assay
Terminal deoxynucleotidyl transferase
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Glioblastoma multiforme is the most deadly primary brain tumor and has no effective treatment. Therefore, it is important to identify novel and effective therapies that impede glioma tumorigenesis. MicroRNAs (miRNAs) are helpful analytical biomarkers and may be useful targets for treating multiple human cancers. Previous reports suggest that miRNA-485-5p is dysregulated and contributes to tumorigenesis in some cancer types. Nevertheless, the biological role of miRNA-485-5p in glioma is not well understood. In this study, we demonstrated that miRNA-485-5p expression was reduced in gliomat issues and cell lines. In addition, miRNA-485-5p overexpression inhibited cell proliferation, migration, and invasion in glioma cell lines. Additionally, we identified Tumor Protein D52 Like 2 (TPD52L2) as a direct target of miRNA-485-5p. Moreover, we showed that miRNA-485-5p regulated glioma tumorigenesis by down-regulating TPD52L2 expression in vitro and in vivo. Our results suggest that miRNA-485-5p is a suppressor of glioma tumorigenesis and could serve as a novel candidate for therapeutic applications in glioma treatment.
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Glioma is a common intracranial malignant tumor with high mortality and high recurrence rate. In recent years, increasing evidence has demonstrated that circular RNAs (circRNAs) are potential biomarkers and therapeutic targets for many tumors. However, the role of circRNAs in glioma remains unclear. In this study, we found that circRNA-0002109 was highly expressed in glioma tissues and cell lines. Downregulation of circRNA-0002109 expression inhibited the proliferation, migration, and invasion of glioma cells and inhibited the malignant progression of tumors in vivo. Investigations into the relevant mechanisms showed that circRNA-0002109 upregulated the expression of EMP2 through endogenous competitive binding of microRNA-129-5P (miR-129-5P), which partially alleviated the inhibitory effect of miR-129-5P on epithelial membrane protein-2 (EMP2) and ultimately promoted the malignant development of glioma. Our results indicate that circRNA-0002109 plays an important role in the proliferation, invasion, and migration of glioma cells by regulating the miR-129-5P/EMP2 axis, which provides a new potential therapeutic target for glioma.
Circular RNA
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Abstract Background Long noncoding RNAs (lncRNAs) play crucial roles in tumor progression and are dysregulated in glioma. However, the functional roles of lncRNAs in glioma remain largely unknown. Methods Using the TCGA and GEPIA2 databases, the overexpression of LINC01578 in glioma tissues was determined and further validated in glioma cell lines. The effects of LINC01578 on proliferation, migration, and invasion in glioma were detected by in vitro and in vivo experiments. RNA immunoprecipitation (RIP), dual luciferase reporter, RNA FISH, and RNA sequencing assays were carried out to elucidate the underlying molecular mechanisms regulated by LINC01578 in glioma. RIP and RT-qPCR was used to analyze the regulatory effect of N 6 -methyladenosine (m 6 A) on aberrantly expressed LINC01578. Results Highly expressed LINC01578 was identified in glioma tissues and was associated with poor prognosis in glioma patients. Functional assays showed that LINC01578 regulates glioma growth and metastasis in vitro and in vivo . Mechanistically, LINC01578 sponged miR-6893-3p to upregulate TRIM14 expression, thereby facilitating glioma progression. Furthermore, LINC01578 was upregulated in response to N 6 -methyladenosine modification, which was attributed to METTL3/YTHDF1-mediated RNA transcripts. Conclusion Our results reveal a novel m 6 A/LINC01578/miR-6893-3p/TRIM14 pathway for glioma progression and suggest LINC01578 as a novel prognostic indicator and therapeutic target for glioma.
Tumor progression
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