MicroRNAs (miRNAs) have been demonstrated to be important in the development and progression of various types of cancer. However, the exact roles of certain anti‑oncogenic miRNAs in human malignant gliomas remain to be elucidated. The present study aimed to reveal the expression of microRNA‑203 (miR-203) in normal brain tissues and gliomas, and to investigate the role of miR-203 in cell proliferation and migration in human glioblastoma U251 cells. Real-time reverse transcription polymerase chain reaction (RT-PCR) showed that the expression of miR-203 in high WHO grade glioma tissues was significantly decreased compared with low WHO grade glioma tissues and normal brain tissues, and its expression demonstrated a decreasing tendency with ascending WHO grades. The transfection of the miR-203 mimic into U251 cells markedly downregulated the expression of phospholipase D2 (PLD2), which was identified as a direct target of miR-203. Furthermore, miR-203 overexpression significantly suppressed the proliferation and invasion of U251 cells, while the overexpression of PLD2 abrogated these effects induced by the miR-203 mimic. In conclusion, the present study demonstrated the clinical significance of miR-203 in gliomas and suggested that miR-203 was able to inhibit the proliferation and invasion of glioma cells, partially at least via suppressing the protein expression of PLD2. Thus, miR-203 may be a novel candidate for the development of therapeutic strategies for gliomas.

Malignant glioma is the most common type of cancer in the central nervous system, with highly invasive characteristics. The Rho-associated protein kinase (ROCK1) has been found to act as key regulator of actin cytoskeleton reorganization, a process closely associated with cancer cell invasion. microRNA-145 (miRNA-145) has been recently shown to act as a suppressor in several types of tumor, including glioma. However, the exact regulatory mechanism by which miR-145 inhibits glioma still remains to be uncovered. In this study, we report that the miR-145 level was significantly reduced in glioma tissues and in the human glioma cell lines U87 and U251, as compared to matched adjacent and normal brain tissues. We then identified the ROCK1 gene as a novel target of miR-145. The expression of ROCK1 was markedly upregulated in glioma tissues, as well as in U87 and U251 cells. Moreover, miR-145 significantly inhibited ROCK1 protein expression in U87 cells. We further show that miR-145 transfection considerably reduced the invasive ability of U87 cells, and was accompanied by the downregulation of matrix metalloproteinase 2 and 9, an effect which could be attenuated by overexpression of ROCK1. In conclusion, the present study suggests that miR-145 can inhibit U87 glioma cell invasion, at least partially via downregulation of the RhoA/ROCK1 pathway. In conclusion, this is the first study to report that ROCK1, as a novel target of miR-145, acts as a positive regulator of glioma cell invasion. Therefore, ROCK1 may constitute a promising target for glioma treatment.

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Objectives Temozolomide (TMZ) resistance is a key factor that restricts the therapeutic effect of glioblastoma (GBM). YTH‐domain family member 2 (YTHDF2) is highly expressed in GBM tissues, while the mechanism of YTHDF2 in TMZ resistance in GBM remains not fully elucidated. Methods The YTHDF2 expression in TMZ‐resistant tissues and cells was detected. Kaplan–Meier analysis was employed to evaluate the prognostic value of YTHDF2 in GBM. Effect of YTHDF2 in TMZ resistance in GBM was explored via corresponding experiments. RNA sequence, FISH in conjugation with fluorescent immunostaining, RNA immunoprecipitation, dual‐luciferase reporter gene and immunofluorescence were applied to investigate the mechanism of YTHDF2 that boosted TMZ resistance in GBM. Results YTHDF2 was up‐regulated in TMZ‐resistant tissues and cells, and patients with high expression of YTHDF2 showed lower survival rate than the patients with low expression of YTHDF2. The elevated YTHDF2 expression boosted TMZ resistance in GBM cells, and the decreased YTHDF2 expression enhanced TMZ sensitivity in TMZ‐resistant GBM cells. Mechanically, YTHDF2 bound to the N6‐methyladenosine (m 6 A) sites in the 3′UTR of EPHB3 and TNFAIP3 to decrease the mRNA stability. YTHDF2 activated the PI3K/Akt and NF‐κB signals through inhibiting expression of EPHB3 and TNFAIP3, and the inhibition of the two pathways attenuated YTHDF2‐mediated TMZ resistance. Conclusion YTHDF2 enhanced TMZ resistance in GBM by activation of the PI3K/Akt and NF‐κB signalling pathways via inhibition of EPHB3 and TNFAIP3.

Trauma is the main cause of death for people aged 1-45, and among them, traumatic brain injury (TBI) is the major condition, which causes over 50,000 deaths each year and costs over 80 billion per year. Tetrahydroxystilbene glucoside (TSG) is the active ingredient of polygonum multiflorum, a traditional Chinese herbal medicine, which presented multiple pharmacological effects, including antioxidative, anti-inflammatory, reducing blood fat and neuroprotection effects. However, the effect of TSG in promoting the recovery of the nerve system after TBI is not fully understood. PARP1 is a key enzyme in repair of the damage in DNA, which is activated by binding to DNA breaks, initiating both single-strand and double-strand DNA break repair. And we thought that overexpression of TSG might enhance the effect of TSG in TBI treatment. In this study, we firstly detected the oxidative stress response related molecules in serum samples of TBI patients and a TBI mice model, and found that oxidative stress response was activated after TBI, and TSG would reduce this effect. We further noticed that inflammation related molecules presented a similar trend with oxidative stress response related molecules. These results indicated that inflammatory response and oxidative stress processes were both activated after TBI, and reduced after TSG treatment. We further detected that the apoptosis related proteins and anti-oxidative proteins were increased after TSG treatment, and these effects were enlarged after overexpression of PARP1. We further noticed that these effects might be mediated by inhibition of the Ras/JNK signalling pathway. Thus, we thought overexpression of PARP1 might enhance the therapeutic effect of TSG in TBI treatment.