Jun Guo

Reactive oxygen species (ROS) modulator 1 (Romo1) is a mitochondrial membrane protein that is essential for the regulation of mitochondrial ROS production and redox sensing. Although the physiological functions of Romo1 have been studied for the past few years, the role of Romo1 in cancer remained unclear. In this study, we found that the high expression of Romo1 is associated with the poor prognosis of glioblastoma patients. Further study revealed that Romo1 is highly expressed in macrophages, indicating that the overexpression of Romo1 may participate in the function of macrophages and contribute to the progression of glioblastoma. Through the glioblastoma mouse model, we found that the overexpression of Romo1 in bone marrow cells significantly inhibited the immune response within tumor microenvironment, and that the overexpression of Romo1 resulted in the M2 polarization of bone marrow derived macrophages (BMDMs) through mTORC1 signaling pathway. In addition, the inhibition of Romo1 combining with anti-PD-1 immunotherapy significantly improved the survival outcome of glioblastoma in mouse model. Collectively, our study highlights the important role of Romo1 in immune response especially the function of macrophages, and implicates it as a potential target of immunotherapy for glioblastoma.

Heat shock cognate protein 70 (Hsc70) is a key mediator for the maintenance of intracellular proteins and regulates cellular activities. And it is elevated in various tumor tissues including glioma, which is closely related to the malignancy and poor prognosis of the tumors. However, the effects of Hsc70 on gliomas and its regulatory mechanism have not yet been elucidated. In the present study, we found that Hsc70 was overexpressed in glioma tissues and cultured glioma cells. Furthermore, Hsc70 expression exhibited positive correlation with the grades of gliomas. Knockdown of Hsc70 could effectively inhibit cell proliferation and increase cell apoptosis. Furthermore, we identified that β4GalT5 was a critical target for Hsc70-mediated anti-glioma effects. Blocking β4GalT5 activity could effectively reverse the anti-tumor effect of Hsc70. Taken together, these data indicate that Hsc70 regulates β4GalT5 levels, and possibly plays a role in cell proliferation and apoptosis of glioma.

MiR-29b inhibits the growth of glioma via MYCN dependent way MiR-29b inhibits the growth of glioma via MYCN dependent way

Gliomas are the most common type of malignant brain tumor. Studies have identified that miR‑15b is negatively correlated with cripto-1 expression in glioma cells, and these molecules serve an important role in cancer development and progression. The current study was undertaken to further examine the association between these two molecules. Fluorescent quantitative PCR confirmed that miR‑15b expression was significantly downregulated in glioma tissue while cripto‑1 expression was significantly increased. Subsequent to transfection with miR‑15b mimics, cripto‑1 expression was significantly suppressed, and dual luciferase reporter assays further demonstrated that miR‑15b regulates cripto‑1 in a targeted manner. Furthermore, miR‑15b inhibited proliferation and invasion, and promoted apoptosis of glioma cells while downregulating the expression of MMP‑2 and MMP‑9. In contrast, cripto‑1 expression had the opposite effects. Co‑transfection with miR‑15b mimics and the cripto‑1 overexpression vector overcame the inhibitory action of miR‑15b on cripto‑1. Therefore, it is suggested that miR‑15b modulates cell growth and invasion through targeted regulation of cripto‑1 expression in glioma cells. This observation may provide novel targets for the prevention and treatment of gliomas.

MicroRNA-15b (miR-15b) has been demonstrated to suppress proliferation by arresting cell cycle progression and inducing apoptosis in glioma cells. However, the prognostic value of miR-15b expression in human gliomas remains unclear. In the present study, the authors examined the expression profile in glioma specimens and the prognostic value of miR-15b in patients with gliomas. Real-time polymerase chain reaction assay was employed to detect the expression levels of miR-15b in 92 glioma tissues categorized by World Health Organization (WHO) histopathological grades. However, the prognostic value of miR-15b in human glioma has not been evaluated yet. MiR-15b expression in human glioma tissues was distinctly lower than in normal brain tissues. Furthermore, the expression of miR-15b notably decreased with the ascending histopathological grade of gliomas. Additionally, Kaplan–Meier survival analysis showed that low miR-15b expression was associated with poor overall survival in patients with gliomas. Similarly, miR-15b reduction occurred with increasing frequency in glioma patients with lower Karnofsky performance scale (KPS) scores than in those with higher KPS scores. No significant difference was observed between miR-15b expression and gender, age, and tumor location. These findings revealed that a lower expression level of miR-15b was closely related to a shorter overall survival, suggesting that miR-15b could be an intrinsic factor that plays an important role in the malignant progression of gliomas.

Aim. To investigate the role and mechanism of miR-15b in the proliferation and apoptosis of glioma.Methods. The miR-15b mimics were transfected into human glioma cells to upregulate the miR-15b expression. Cyclin D1 was determined by both western blotting analysis and luciferase reporter assay. Methylthiazol tetrazolium (MTT) and flow cytometry were employed to detect the cell proliferation, cell cycle, and apoptosis.Results. Overexpression of miR-15b inhibits proliferation by arrested cell cycle progression and induces apoptosis, possibly by directly targeting Cyclin D1. Both luciferase assay and bioinformatics search revealed a putative target site of miR-15b binding to the 3′-UTR of Cyclin D1. Moreover, expression of miR-15b in glioma tissues was found to be inversely correlated with Cyclin D1 expression. Enforced Cyclin D1 could abrogate the miR-15b-mediated cell cycle arrest and apoptosis.Conclusions. Our findings identified that miR-15b may function as a glioma suppressor by targeting the Cyclin D1, which may provide a novel therapeutic strategy for treatment of glioma.