MicroRNA-351 Promotes the Proliferation and Invasion of Glioma Cells through Downregulation of NAIF1.

Despite the well-characterized expression profile of miR-351 in the neural system, its molecular mechanisms in glioma still remain elusive. Here we intended to assess the regulatory function of miR-351 on nuclear apoptosis-inducing factor 1 (NAIF1) and, thereby, modulation of cancerous behaviors of human glioma cell lines. Two human glioma cell lines (U87 and U251) and normal human astroglia (NHA) cell line were cultured. The cell lines were prepared and transfected with mimic, inhibitor, and negative controls (NCs) of miR-351, then MTT and wound healing assays were performed. We extracted the total protein for western blotting assay and isolated the total RNA for real-time PCR. The miR-351 expression was significantly decreased in U87 and U251 cell lines compared with the NHA cell line (P < 0.05). NAIF1 expression was significantly higher in glioma cell lines compared with the NHA cell line (P < 0.05). Moreover, the NAIF1 expression showed a negative correlation with miR-351 (P = 0.005, r = -0.522). Apoptosis was significantly decreased in both cell lines transfected with miR-351 mimics compared with the NC group at 72 and 96 h after transfection (P < 0.05) and significantly increased in the transfected group with miR-351 inhibitors compared with the NC group at 72 and 96 h after transfection (P < 0.05). According to our results, after 24 and 48 h, migration was increased in the mimic group compared with the miR-351 NC group and decreased in the inhibitory group compared with the miR-351 NC group in the U251 cell line. Our findings provide theoretical evidence that miR-351, which targets NAIF1, could be considered an important marker in the pathogenesis of glioma. Furthermore, miR-351 has valuable potential to serve as a new prognostic and diagnostic biomarker and could be considered a potential target for the treatment of this cancer in the near future.

Correction to: MicroRNA-351 Promotes the Proliferation and Invasion of Glioma Cells through Downregulation of NAIF1.

The original version of this article unfortunately contained mistakes in the Affiliation section.

Ubiquitin-specific protease 4 promotes glioblastoma multiforme via activating ERK pathway.

BACKGROUND: Glioblastoma multiforme (GBM) is one of the most common brain tumors in adults. Current treatments cannot increase survival to a large extent, as the glioblastoma development mechanisms remain unknown. It has been well documented that ubiquitination contributes to tumor initiation and/or progression in many kinds of cancer. Ubiquitin-specific protease 4 (USP4), a member of deubiquitinating enzymes (DUBs) family, can remove ubiquitin residues and play a role in cancer development. METHODS: In the current study, lentiviruses were used to manipulate the expression of USP4. Real-time PCR and Western blot were used to measure the expression level of USP4. Then, CCK-8 and annexin-V staining were used to detect cell proliferation and cell apoptosis, respectively. RESULTS: First, we found that USP4 was highly upregulated in GBM tissues in comparison with that in normal tissues and high level of USP4 correlated with poor prognosis. Moreover, knockdown of USP4 could significantly inhibit cell proliferation and increase cell apoptosis in U87 and T98G cells. Cells with stable USP4 reduction exhibited slower tumor growth rate and smaller tumor size than the control group cells in a xenograft mouse model. Inhibition of USP4 downregulated the expression of PCNA, Bcl-2 and p-ERK1/2, but upregulated the expression of Bax both in vitro and in vivo. Inversely, USP4 overexpression could attenuate the effects contributed by ERK inhibitor. TGF-ßR inhibition reduced level of TGF-ßR1, p-smad2 and p-ERK1/2 which can partially be rescued by USP4 overexpression. CONCLUSION: USP4, as a potential novel oncogene, promotes GBM by activation of ERK pathway through regulating TGF-ß.