Upregulated miRNA-622 inhibited cell proliferation, motility, and invasion via repressing Kirsten rat sarcoma in glioblastoma.

Glioblastoma has been reported as one of the leading causes of cancer-related death, and some factors including oncogenic genes and environments are involved in tumorigenesis. MicroRNAs (miRNAs) act as a kind of small and noncoding RNA, which can target the downstream molecules. Emerging reports demonstrate that microRNAs regulate the initiation and progression of different cancers. In the present study, we conducted in vitro experiment as well as clinical studies in a cohort of 20 glioblastoma samples. We demonstrated that miR-622 expression was lower in tumor tissues and cells, when compared to normal brain tissues and normal human astrocyte (NHA) cells, while K-Ras messenger RNA (mRNA) and protein showed the opposite expression profile. Overexpression of miR-622 suppressed tumor cell proliferation, migration, and invasion of A172, U87, and U251 cells. Accordingly, the proliferating cell nuclear antigen (PCNA), matrix metallopeptidase 2 (MMP2), and MMP9 expressions were also decreased due to miR-622 overexpression. Importantly, we discovered that wild Kirsten rat sarcoma (K-Ras) was a direct target of miR-622, which decreased the expression of K-Ras protein in A172, U87, and U251 cells. In conclusion, upregulated miRNA-622 inhibited cell proliferation, migration, and invasion via repressing K-Ras in the progression of glioblastoma, and miR-622-K-Ras pathway can be recommended as a potential target for treatment of glioblastoma.

Geranylgeranyltransferase I regulates HIF-1α promoting glioblastoma cell migration and invasion.

Glioblastoma multiforme is a highly migratory and invasive brain tumor in which hypoxia inducible factor-1α (HIF-1α) plays important roles. However, the underlying mechanisms regulating the action of HIF-1α in glioma cell migration and invasion ability remain unclear. We reported here that HIF-1α was regulated by geranylgeranyltransferase I (GGTI), a protein prenylation transferase, and then promoted glioma cell migration and invasion. The migratory and invasive ability of glioma cells were enhanced by hypoxia treatment but inhibited by down-regulation of HIF-1α. GGTI activity inhibition or GGTI specific ß subunit (GGTI ß) knocking-down decreased HIF-1α protein level. In addition, down-regulation of GGTI ß inhibited migration and invasion of glioma cells under hypoxia, while GGTI ß over-expression promoted it. Furthermore, the effect of GGTI ß over-expression on cell migration and invasion was abolished by HIF-1α down-regulation. In summary, our study showed, for the first time, that HIF-1α was regulated by protein prenylation transferase GGTI and mediated the effect of GGTI on glioma cell migration and invasion.

Challenges in Using the Posterior Inferior Cerebellar Artery for Revascularization of the Anterior Inferior Cerebellar Artery: A Microsurgical Anatomic Study.

BACKGROUND: A bypass is usually required to prevent ischemia during the treatment of anterior inferior cerebellar artery (AICA) aneurysms. The intracranial (IC)-to-IC bypass provides several advantages over the extracranial-to-IC bypass in the posterior fossa. However, there are only 2 case reports about AICA revascularization with the posterior inferior cerebellar artery (PICA). We aimed to investigate the microsurgical anatomical challenges for PICA to AICA anastomosis. METHODS: Ten cadaveric heads injected with colored silicone were inspected on both sides using a lateral transcondylar approach. After the donor and recipient arteries were examined from the posterior side, neurovascular contents of the posterior fossa were excised and the origin, course, and variations of both arteries were investigated from the anterior view. The diameters of the AICA and PICA segments and the intersegment distance were measured. RESULTS: PICA variations and posteromedial origins from the vertebral artery were identified in 8 of the 20 right and 6 of the 20 left sides, and the first segment of the PICA was not present in 7 sides. Furthermore, in 18 sides, the PICA was trapped between the lower cranial nerves and dentate ligaments. Therefore the donor artery could not be brought closer than 1 cm to the recipient artery in 19 sides. Moreover, AICA variations were identified in 6 sides, and in 12 sides, the diameter of the recipient artery was <1 mm. CONCLUSIONS: The mostly PICA-related issues made PICA-to-AICA anastomosis unfeasible in all cadaveric heads included in the study.

Geranylgeranyltransferase I promotes human glioma cell growth through Rac1 membrane association and activation.

Geranylgeranyltransferase I (GGTase-I) is responsible for the posttranslational lipidation of several signaling proteins such as RhoA, Rac1, and Cdc42, which contribute to tumor development and metastasis. However, the role of GGTase-I in the progression of human glioma is largely unknown. Here, we provide the evidence that Rac1 mediates the effects of GGTase-I on the proliferation and apoptosis in human glioma cells. We found that GGTase-I was abundantly expressed in human primary glioma tissues. Inhibition or downregulation of GGTase-I markedly decreased the proliferation of glioma cells and induced their apoptosis, while overexpression of GGTase-I promoted cell growth in vitro. Inactivation of GGTase-I eliminated geranylgeranylation of RhoA and Rac1, prevented them from targeting to the plasma membrane, and inhibited Rac1 activity. Furthermore, overexpressing wild type or constitutively active Rac1 stimulated glioma cell growth, similar to the effect of GGTase-I overexpression. Importantly, overexpressing dominant-negative Rac1 or Rac1 with the prenylation site deleted or mutated abrogated GGTase-I-induced proliferation in glioma cells. These results confirm the view that geranylgeranylation is essential to the activity and localization of Rho family proteins and suggest that Rac1 is required for GGTase-I-mediated glioma growth.