Abstract
Malignant glioma is the most common type of primary brain tumor in adults, characterized by rapid tumor growth and infiltration of tumor cells throughout the brain. Alterations in the activity of the 26S proteasome have been associated with malignant glioma cells, although the specific defects have not been identified. Recently, microRNA-326 (miR-326) was shown to play an important role in glioblastoma and breast cancer, but the underlying molecular mechanisms remain unclear. In the present study, the human Nin one binding protein (NOB1) was identified as a direct target of miR-326 and a potential oncogene in human glioma. Similar to NOB1 silencing by shRNA, overexpression of miR-326 in human glioma cell lines (A172 and U373) caused cell cycle arrest at the G1 phase, delayed cell proliferation and enhanced apoptosis. MiR-326 inhibited colony formation in soft agar and decreased growth of a xenograft tumor model, suggesting that miR-326 and NOB1 are required for tumorigenesis in vitro and in vivo. Furthermore, these processes were shown to involve the MAPK pathway. NOB1 overexpression in human glioma samples was detected by Affymetrix array analysis, and NOB1 mRNA and protein levels were shown to be increased in high-grade glioma compared to low-grade glioma and normal brain tissue. Furthermore, high levels of NOB1 were associated with unfavorable prognosis of glioma patients. Taken together, these results indicate that miR-326 and NOB1 may play an important role in the development of glioma.
Highlights
Gliomas are aggressive lethal solid brain tumors arising from support cells in the central nervous system
Cell Culture HEK293T cells and human glioma cells A172, U373 and U87 obtained from the American Type Culture Collection (ATCC) were cultured in DMEM supplemented with 10% fetal bovine serum, 100 U/mL of penicillin and 100 mg/mL of streptomycin
Pre-hsa-miR-326 RNAs or non-functional control miR-NC RNAs were co-transfected with the above-mentioned reporter vectors into the human glioma cell line U87
Summary
Gliomas are aggressive lethal solid brain tumors arising from support cells in the central nervous system. The major histological subtypes of gliomas are astrocytomas, oligodendrogliomas and oligoastrocytomas. Astrocytomas, which amount to 80–85% of all gliomas, are graded from low (grade I–II) to high (grade III–IV) based on histopathological characteristics [1]. Grade IV astrocytomas are known as glioblastoma multiforme (GBM), which is the most common and lethal type of adult gliomas and is associated with a poor prognosis. MicroRNAs (miRNAs) function as regulatory molecules by inhibiting protein translation, and they play important roles in development, differentiation, cell proliferation, and apoptosis [5]. Downregulation of miRNAs has been suggested to play a critical role in cancer progression [6,7,8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
