Abstract. Glioblastoma is the most common primary malignancy of the adult central nervous system (CNS) and is associated with an exceptionally poor prognosis. Elucidation of the pathogenesis and molecular changes will help us to further understand the pathogenesis and progression of the disease and offer new therapeutic targets. FUS1 (TUSC2, tumor suppressor candidate 2) is a tumor-suppressor gene located on human chromosome 3p21. Restoration of FUS1 function in human non-small cell lung cancer (NSCLC) cells was found to significantly inhibit tumor cell growth and modulate the chemosensitivity of lung cancer cells. Yet, its role in human glioblastoma has rarely been addressed. In the present study, we demonstrated that low expression of FUS1 was detected in high-grade human glioma, implying that FUS1 expression is negatively associated with progression of the disease. Subsequent studies confirmed that FUS1 overexpression inhibited the proliferation, migration and invasion of human glioblastoma cells. In addition, we found that FUS1 overexpression significantly upregulated miR-197 expression in the glioblastoma cells. We also revealed that miR-197 suppressed the proliferation, migration and invasion of the cells as well as the silencing of miR-197 attenuated the biological functions of FUS1. Using human glioblastoma tissue samples, we demonstrated that miR-197 is negatively associated with metastasis. All the results demonstrated that FUS1 acts as a tumor-suppressor gene by upregulating miR-197 in human glioblastoma and implied that restoration of FUS1 and miR-197 could be new therapeutic strategies for glioblastoma.

Gliomas are the most common type of malignant primary brain tumors in adults and exhibit a spectrum of aberrantly aggressive phenotypes. Despite advances in treatments during past decades, prognosis of the disease remains poor, with a median survival time of 12–14 months. Future studies on the molecular mechanism of the disease may provide the theoretical basis to identify new targets for effective therapies. The present study revealed that in glioblastoma cells, the overexpression of cytochrome P450, family 27, subfamily A, polypeptide 1 (CYP27A1) promoted proliferation, while silencing of CYP27A1 inhibited proliferation, without affecting migration and invasion. CYP27A1 protein was upregulated in glioblastoma tissues, indicating that CYP27A1 is an oncogene. The downregulation of specific microRNAs (miRNA) may contribute to the upregulation of oncogenes in glioblastoma. A common strategy was used to predict target miRNAs of CPY27A1 using the miRanda algorithm. miR-211 and miR-204 could target the 3′untranslated region of CPY27A1 mRNA. Additional studies confirmed that the overexpression of miR-204 inhibited CPY27A1 expression in glioblastoma cells. Finally, it was identified that miR-204 was downregulated in glioblastoma and that its overexpression inhibited proliferation, migration and invasion in glioblastoma cells. Thus, it was concluded that miR-204 functions as a tumor suppressor gene, at least partly by suppressing CYP27A1 in glioblastoma.

Glioblastoma is a type of glioma with a relatively higher degree of malignancy that may result in severe intracranial hypertension and focal symptoms. Surgery is the preferred treatment modality. Combination therapy including radiotherapy, chemotherapy, gene therapy, immunotherapy and targeted therapy have also been employed. However, due to the invasiveness and pathogenesis of the disease, such treatments do not yield satisfactory outcomes. The aim of the present study was to examine the expression of microRNA (miR)-184 in Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in the mechanism of glioblastoma formation, thus providing a new basis for the mechanism of glioblastoma induction. The LN18 cell line was employed in the present study. After undergoing thawing, culturing and passaging processes, the cells were divided into the set control group, miR-184 mimic group (transfer miR-184 simulator) and miR-184 group. The expression of miR-184 was detected using quantitative polymerase chain reaction. An MTT assay was used to detect the proliferation ability of glioma cells, and clone formation ability was also detected. The cell scratch and invasion assays were used to identify the cell invasion ability. Western blotting was performed to detect the expression level of p-JAK2 and p-STAT3 proteins. The results showed that compared to the control group, the expression of miR-184 in the miR-184 mimic group increased. Cell proliferation, as well as clone formation and invasion ability were enhanced. The number of cells penetrating septum, as well as the expression of p-JAK2 and p-STAT3 proteins were increased. Differences were statistically significant (P<0.05). By contrast, compared to the control group, the expression of miR-184 in the miR-184 inhibitory group decreased. Cell proliferation, as well as clone formation and invasion ability were reduced. The number of cells penetrating septum, as well as the expression of p-JAK2 and p-STAT3 proteins were reduced. Differences were statistically significant (P<0.05). In conclusion, the results of the present study have shown that miR-184 may be involved in the formation of glioblastoma and influence the expression of JAK2/STAT3 signaling pathway.

The aim of the study was to investigate the anti-tumoral activity of morelloflavone substances with different structures. We also studied the possible link between morelloflavone structure and its function. Various types of chromatographic techniques were used to isolate and screen morelloflavone substances from the extracts of gambogic tree trunk and the morelloflavone structures were identified by analytical techniques such as high resolution mass spectrometry and nuclear magnetism. Anti-tumoral activities of different compounds were investigated and the link between the antitumor activity and the structure of compound was exaimed. Our results showed that the isolated morelloflavone substances demonstrated a certain level of antitumor activity. The compound no. 1 had the strongest effect to inhibit glioma U87 and C6 cells followed by compound no. 2 while compound no. 5 was the weakest among them. We conducted a preliminary analysis on the structure-function relationship through the structure comparison and we concluded that the antitumor effects of morelloflavone substances with different structures were significantly different from each other. Thus, the glucose chain in C4 position of biflavone structure can enhance the antitumor activity of the compound in glioma cells. Additionally, the formation of intramolecular hydrogen bonds in biflavone compounds may also play a role in enhancing the antitumor activity and inhibition rate.