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Objective: We hypothesized that microRNAs (miRNAs) may be involved in tumor development by critically regulating cancer stem cell (CSC) markers in early stages of colon cancer (eCC). The aim of this study was to determine the expression profiles of miRNAs in CSC-positive eCC patients and to examine their associations with recurrence. Materials and Methods: We analyzed CD133, LGR5 and SOX2 expression profiles to determine CSC status in 30 eCC specimens. Then, using the results of RT2 miRNA PCR custom arrays, we evaluated the expression profiles of 38 miRNAs in CSC-positive eCC patients. Results: Recurrence occurred in 5 patients within 10 years after surgery. We determined down-regulation of miR-125b and up-regulation of miR-135b were significant in CSC-positive eCC patients (P= 0.021, P= 0.001, respectively). We found that low expression of miR-125b was associated with recurrence in eCC (P= 0.0022). Conclusion: We suggest that recurrence might be prevented by increasing expression of miR-125b in eCC.

ObjectiveThe appropriate treatments for the different molecular subgroups of medulloblastomas are challenging to determine. Hence, this study aimed to examine the expression profiles of long non-coding RNAs (LncRNAs) to determine a marker that may be important for treatment selection in these subgroups.MethodsChanges in the expression of LncRNAs in the tissues of patients with medulloblastoma, which are classified into four subgroups according to their clinical characteristics and gene expression profiles, were examined via reverse transcription polymerase chain reaction. Moreover, there association with patient prognosis was evaluated.ResultsThe expression levels of MALAT1 and SNGH16 were significantly higher in patients with group 3 medulloblastoma than in those with other subtypes. Patients with high expression levels of MALAT1 and SNGH16 had a relatively shorter overall survival than those with low expression levels.ConclusionsPatients with group 3 medulloblastoma have a high MALAT1 level, which is associated with poor prognosis. Therefore, MALAT1 can be a new therapeutic target in medulloblastoma.

Objective: This study was designed to conduct molecular classification based on IDH1/2, TERT, ATRX, and DAXX changes in pediatric and adult primary glioblastoma (GB) and to analyze the potential interaction of LncRNA MALAT1 in the determined homogeneous subgroups. Methods: We analyzed the expression profiles of ATRX/DAXX and MALAT1 using the qRT-PCR method and IDH and TERT mutation status using DNA sequencing analysis in 85 primary pediatric and adult GB patients. Results: IDH1 mutation was observed in 5 (5.88%) and TERT mutation in 65 (76.47%) primary pediatric and adult GB patients. ATRX and DAXX were detected in 18 (21.18%) and 7 (8.24%) patients. TERT mutation and loss of ATRX/DAXX were associated with short overall survival (p < 0.001, p < 0.001, respectively). Patients carrying especially TERT C228T mutation had worse prognosis (p < 0.001). Six subgroups were obtained from the genetic analysis. Among the subgroups, MALAT1 was highly expressed in group A that had a single TERT mutation as compared to that in groups D and E (p = 0.001 and p < 0.001, respectively); further, high MALAT1 expression was associated with worse prognosis in patients with C228T mutation (p < 0.001). Conclusions: Our findings highlight that the presence of TERT C228T mutation and expression of MALAT1 can be used as primary targets during the follow-up of primary GB patients and in the development of new treatment strategies.

Background: Glioblastoma (GB) is the most aggressive form of brain tumor. Despite the current treatment methods, the survival rate of patients is very low. Therefore, there is a need to develop new therapeutic agents. The migration and invasion capacity of GB cells is related to mesenchymal transition (MT) mechanism. Materials and Methods: The effect of OLE on MT was determined by analysis of the Twist, Snail, Zeb1, N-cadherin and E-cadherin genes in the EMT mechanism. The effect of OLE on cell migration was determined by wound healing test. Results: 2 mg/ml OLE reduced Twist, Snail, Zeb1 and N-cadherin expression and the combination of OLE + TMZ (2 mg/ml OLE + 350 mM TMZ) increased E-cadherin and reduced Twist, Zeb1 and N-cadherin. In addition, co-treatment with OLE increased TMZ-induced anti-invasion properties thought suppressing transcription factors of MT mechanism. Conclusion: OLE can enhance the anti-MT activities of TMZ against GB and provide strong evidence that combined treatment with OLE and TMZ has the potential to be an effective alternative approach in GB therapy.

Glioblastoma (GBM) is the most prevalent and deadliest subtype of glioma. Despite current innovations in existing therapeutic modalities, GBM remains incurable, and alternative therapies are required. Previously, we demonstrated that Olea europaea leaf extract (OLE) kills GBM cells by modulating miR-181b, miR-137, miR-153 and Let-7d expression. However, although oleuropein (OL) is the main compound in OLE, its role in the antitumour effect of OLE remains unknown. This study determined the effect of OL on GBM cell line T98G and compared the results with our previous findings regarding the effect of OLE on the same cell line. The antiproliferative activity of OL and its effect on temozolomide (TMZ) response were tested inT98G cells using WST-1 assay. OL inhibition was evaluated using one-way analysis of variance with Tukey’s post hoc test. The effect of OL on miR-181b, miR-137, miR-153 and Let-7d expression was assessed using quantitative reverse transcription polymerase chain reaction. Fold differences in expression between untreated, OL or OL + TMZ-treated samples were calculated using 2−ΔCt method. Significance was evaluated using an independent sample t-test. Treatment with 277.5 and 555 µM OL resulted in 39.51% and 75.40% reductions in T98G cells within 24 h. Coadministration of 325 µM TMZ and 277.5 or 555 µM, OL caused 2.08- and 2.83-fold increases, respectively, in the therapeutic effect of TMZ. OL + TMZ significantly increased microRNA expression, particularly Let-7d, than OLE. In conclusion, OL has an antitumour effect on GBM cells mainly via regulation of Let-7d expression. The present results also indicate other minor compounds in OLE play important anticancer roles.

Introduction: The noncoding RNAs (ncRNAs) play a role in biological processes of various cancers including gliomas. The majority of these transcripts are uniquely expressed in differentiated tissues or specific glioma types. Pediatric oligodendroglioma (POG) is a rare subtype of diffuse glioma and accounts for Methods: We investigated the levels of 13 known miRNAs and 6 LncRNAs in tumor samples from 9 patients with primary POG by using RT-PCR and analyzed their association with outcomes. Results: The expression levels of miR-21, miR-106a, miR-10b, and LncRNA NEAT1 were higher, and the expression level of miR-143 was lower in POG tissues compared with normal brain tissues (p = 0.006, p = 0.032, p = 0.034, p = 0.002, and p = 0.001, respectively). High levels of NEAT1 and low expression of miR-143 were associated with decreased probability of short disease-free survival (p = 0.018 and p = 0.022, respectively). Discussion: NEAT1 and miR-143 levels could serve as reciprocal prognostic predictors of disease progression in patients with POG. New treatment models to regulate the expression levels of NEAT1 and miR-143 will bring a new approach to the therapy of POG.

Glioblastoma (GB) is the most aggressive form of brain tumor. Despite the current treatment methods, the survival rate of patients is very low. Therefore, there is a need to develop new therapeutic agents. The migration and invasion capacity of GB cells is related to mesenchymal transition (MT) mechanism.The effect of OLE on MT was determined by analysis of the Twist, Snail, Zeb1, N-cadherin and E-cadherin genes in the EMT mechanism. The effect of OLE on cell migration was determined by wound healing test.2 mg/ml OLE reduced Twist, Snail, Zeb1 and N-cadherin expression and the combination of OLE + TMZ (2 mg/ml OLE + 350 mM TMZ) increased E-cadherin and reduced Twist, Zeb1 and N-cadherin. In addition, co-treatment with OLE increased TMZ-induced anti-invasion properties thought suppressing transcription factors of MT mechanism.OLE can enhance the anti-MT activities of TMZ against GB and provide strong evidence that combined treatment with OLE and TMZ has the potential to be an effective alternative approach in GB therapy.

Introduction: Glioblastoma (GB) is the most aggressive primary brain tumour. Temozolomide (TMZ) is a chemotherapy drug used in the treatment of GB. Despite treatment with TMZ, the prognosis of GB is poor. This study aimed to demonstrate the ability of Olea europaea leaf extract (OLE) alone and in combination with TMZ to suppress tumour aggressiveness by evaluating long non-coding RNA (LncRNA) and cancer stem cell (CSC) markers in GB cells using a three-dimensional (3D) model. Methods: The Real-time PCR (RT-PCR) method was used to determine the effects of OLE on LncRNA and CSC markers associated with tumour aggressiveness. To explore the effect of OLE on tumour size, a 3D model was developed. Results: It was found that OLE suppressed tumour aggressiveness with inhibited the MALAT1, SOX2 and NANOG ( p < 0.05). OLE + TMZ also inhibited MALAT1, LOXL1-AS1, PVT1 and H19 ( p < 0.05) and OCT4, NANOG, SOX2 and CD133 ( p < 0.05). In addition, to reduce tumour aggressiveness in a 3D cell culture, the use of OLE and OLE + TMZ has been supported (47.11-fold, p < 0.0001 and 18.04-fold, p < 0.0001, respectively). Conclusion: OLE may be a potential therapeutic agent that can be used in the treatment of GB, as it has been shown to reduce tumour size and increase the effect of TMZ.

The red-orange pigment producer strain Penicillium mallochii (TACB-16) used in this study was isolated from beech tree bark in Balikesir, Turkey, and was identified by molecular methods (P. mallochii Genbank accession number: MG591446). P. mallochii Rivera, Urb & Seifert was first isolated from the caterpillars Rothschildia lebeau and Citheronia lobesis on Costa Rica and is a new record for Turkey. Little is known of this fungus. In this study, the pigment production of P. mallochii on different media was characterised, and the factors affecting the pigment production and efficacy against the human GB cell line T98G cell viability/cytotoxicity were inspected. The results showed that the pigment was resistant to different temperatures and pH values. The -250 base pair of the ITS region was sequenced and submitted to the Genbank. The blast result of the sequence showed that our isolate displayed maximum similarity (100%) to P. mallochii. Glioblastoma (grade-IV astrocytoma, WHO) is the most lethal subtype of glioma and the survival rate of GB patients is still low. Our results suggest that the pigment exhibits anti-proliferative effects on the T98G cell line. The present study is the first to assess the cytotoxic effect of the pigment on the survival of GB cells. Further studies and validations are needed, but we suggest that the pigment might be used for in vitro and in vivo studies, food industry and for future medical drug studies. Research Foundation of Balikesir University (2017/075) Firat University Scientific Research Projects Management Unit