MicroRNA-134 modulates glioma cell U251 proliferation and invasion by targeting KRAS and suppressing the ERK pathway

Abstract

Dysregulated microRNA-134 (miR-134) has been observed in glioma carcinogenesis, and studies suggested that the ERK pathway plays vital roles in glioma cell growth and proliferation. However, the fundamental relationship between miR-134 and the ERK pathway in glioma has not been fully explained. As a result, this study was aimed to explore the underlying functions of miR-134 in human glioma. Intentionally overexpressed or inhibited miR-134 expression resulted from the transfection of miR-134 mimics, or miR-134 inhibitor within glioma cell line U251 was detected using RT-PCR. Both cell counting kit-8 (CCK-8) assays and Transwell assays were carried out to clarify the proliferation and invasion of U251 cells transfected with miR-134 mimics or miR-134 inhibitors. Our findings showed that miR-134 was significantly downexpressed in glioma tissues, and low miR-134 expression was significantly related to high histopathological grades. However, upregulated miR-134 expression restrained the proliferation and invasion of U251 cells in vitro. Kirsten rat sarcoma viral oncogene (KRAS), a vital factor for the ERK pathway, was directly targeted by miR-134 through its binding with the 3'-UTR of KRAS in glioma. Furthermore, KRAS expression exhibited a positive correlation with the activity of the ERK pathway. Overexpression of KRAS without 3'-UTR partly offsets the suppressive effect of miR-134 on glioma progression. Our data also indicated that miR-134 negatively modulated glioma progression and upregulated miR-134 triggered aberrant activation of the ERK pathway by targeting KRAS. Therefore, miR-134 might be considered as a benign therapeutic target of glioma.

CLIC1 Promotes the Progression of Gastric Cancer by Regulating the MAPK/AKT Pathways

“…We observed that relatively more Bax–Bax homodimers induced apoptosis. The phosphorylation of ERK is crucial for the activation of the MAPK/ERK pathway ,and it was associated with apoptosis, metastasis of tumors [38, 39]. On the other hand, the phosphorylation of AKT is also crucial for the activation of the PI3K/AKT pathway, and it was associated with apoptosis, angiogenesis of tumors [40, 41].…”

miR-134: A Human Cancer Suppressor?

“…In addition, miR-134 was also demonstrated to downregulate in glioma tumor and overexpressed miR-134 inhibited glioma cell growth through targeting KRAS and activating the ERK pathway 39 . Overexpression of miR-134 significantly repressed cell proliferation and xenograft development in another investigation of glioblastoma tumor 40 .…”

“…In glioma, after miR-134 was infected into U251 cells, cell invasion was noticeably reduced through targeting KRAS 39 . In another investigation of glioblastoma, overexpression of miR-134 significantly inhibited U87 cell invasion and metastasis through targeting Nanog mRNA in glioblastoma 41 .…”

Differential transcription profiles of long non-coding RNAs in primary human brain microvascular endothelial cells in response to meningitic Escherichia coli

“…Meningitic E. coli strain infection of primary hBMECs, as well as U251 cells and HUVECs, was performed in accordance with previously described methods6162. Briefly, E. coli overnight culture was resuspended and diluted in serum-free medium and added to the starved confluent primary hBMEC monolayer grown in 10-cm dishes at a multiplicity of infection of 10 (approximately 10 8 colony-forming units per dish) to allow invasion at 37 °C for 3 h. For cytokine stimulation, recombinant human IL-8, MIP-2, GRO-α, IL-1β, IL-6 and TNF-α were purchased from Novoprotein Scientific (Shanghai, China) and used at a final concentration of 10 ng/mL to stimulate the primary hBMECs for 24 h. Finally, cells were washed three times with chilled PBS and subjected to RNA extraction by using TRIzol reagent (Invitrogen, Carlsbad, CA, USA), in accordance with the manufacturer’s instructions.…”