miRNA-660-3p inhibits malignancy in glioblastoma via negative regulation of APOC1-TGFß2 signaling pathway.

Glioblastoma as the most common and aggressive central nervous system tumor in adults. Its prognosis and therapeutic outcome are poor due to the limited understanding of its molecular mechanism. Apolipoprotein C-1 (APOC1) as a member of the apolipoprotein family that acts as a tumor promoter in various cancers. MicroRNA (miRNA) can silence gene expression and suppress tumor progression. However, the role of APOC1 and its upstream miRNA has not been explored in glioblastoma. Two glioblastoma cell lines (U87 and U251) were used to explore the role of APOC1 and its upstream miRNA-660-3p in glioblastoma tumorigenesis in vitro. Cells with APOC1/miRNA-660-3p overexpression or knockdown were assessed for their proliferation, migration, and invasion in vitro, and tumorigenesis in vivo. Gene and protein expression was assessed by qRT-PCR and western blot, respectively. Cell proliferation was assessed by the MTT assay and the EdU and Ki67 staining. Cell migration and invasion were assessed by the transwell assay. Tumorigenesis in vivo was assessed in U87 cells with a xenograft mouse model. APOC1 was overexpressed in glioblastoma compared with normal peritumoral tissue and was inversely related to patient prognosis. APOC1 overexpression promotes cell proliferation, migration, and invasion in vitro. APOC1 inhibition reduced tumor growth in vivo. miRNA-660-3p inhibits tumorigenesis by directly targeting APOC1. Mechanistically, APOC1 drives the malignancy of glioblastoma by activating the TGFß2 signaling pathway. miRNA-660-3p suppresses tumorigenesis by targeting APOC1. Therefore, miRNA-660-3p/APOC1 axis can serve as potential intervention targets in managing glioblastoma progression.

Noncoding RNAs in pediatric brain tumors: Molecular functions and pathological implications.

Brain tumors are common solid pediatric malignancies and the main reason for cancer-related death in the pediatric setting. Recently, evidence has revealed that noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs), play a critical role in brain tumor development and progression. Therefore, in this review article, we describe the functions and molecular mechanisms of ncRNAs in multiple types of cancer, including medulloblastoma, pilocytic astrocytoma, ependymoma, atypical teratoid/rhabdoid tumor, glioblastoma, diffuse intrinsic pontine glioma, and craniopharyngioma. We also mention the limitations of using ncRNAs as therapeutic targets because of the nonspecificity of ncRNA targets and the delivery methods of ncRNAs. Due to the critical role of ncRNAs in brain oncogenesis, targeting aberrantly expressed ncRNAs might be an effective strategy to improve the outcomes of pediatric patients with brain tumors.

Allicin Inhibits Proliferation by Decreasing IL-6 and IFN-ß in HCMV-Infected Glioma Cells.

PURPOSE: Allicin, an extract of garlic, has antitumor effects in multiple tumor types. However, the efficacy of allicin for treating glioblastoma has not yet been examined. This study examined the antitumor effect of allicin on human cytomegalovirus (HCMV)-infected glioblastoma multiforme (GBM) and its role in cytokine signaling. MATERIALS AND METHODS: HCMV-infected glioblastoma was modeled by transfection of U87MG glioblastoma cells with HMCV proteins. MTT assay was used to assess the effect of allicin on the proliferation of glioma cells. Western blot analysis was used to detect the effect of allicin on the expression of intermediate-early gene 2 (IE2) and p53. Reverse transcription-quantitative polymerase chain reaction was used to assess and the levels of interleukin (IL)-6 and interferon (IFN)-ß. Single cell gel electrophoresis was used to analyze changes in radiotherapy-induced DNA damage. RESULTS: Transfection of the IE2 protein led to decreased p53 expression and increased glioblastoma cell proliferation. Allicin inhibited this proliferation in a dose- and time-dependent manner. An inhibitory effect on cytokine release was observed in GBM cells treated with allicin. After treatment with allicin, p53 levels increased significantly, whereas expression of the inflammatory factors such as IL-6 and IFN-ß decreased. U87MG cells treated with allicin and 10 Gy irradiation had increased intracellular DNA damage compared to either treatment alone. CONCLUSION: Allicin inhibited proliferation of glioblastoma cells in vitro. Allicin also inhibited cytokine release, upregulated p53 activity, and increased the sensitivity of glioblastoma to radiotherapy. These results suggest that allicin is effective against HCMV-infected glioblastomas.