Serine/arginine-rich splicing factor 7 (SRSF7), a known splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N⁶-methyladenosine (m⁶A) co-methylation network analysis across diverse cell lines, we find that the gene expression of SRSF7 is positively correlated with glioblastoma (GBM) cell-specific m⁶A methylation. We then indicate that SRSF7 is a novel m⁶A regulator, which specifically facilitates the m⁶A methylation near its binding sites on the mRNAs involved in cell proliferation and migration, through recruiting the methyltransferase complex. Moreover, SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m⁶A methyltransferase. The two m⁶A sites on the mRNA for PDZ-binding kinase (PBK) are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Together, our discovery reveals a novel role of SRSF7 in regulating m⁶A and validates the presence and functional importance of temporal- and spatial-specific regulation of m⁶A mediated by RNA-binding proteins (RBPs).
Humans ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glioblastoma/genetics* ; Methyltransferases/metabolism* ; RNA Splicing Factors/metabolism* ; RNA, Messenger/genetics* ; RNA-Binding Proteins/metabolism* ; Serine-Arginine Splicing Factors/metabolism* ; RNA Methylation/genetics*

Objective To investigate the indications of optic canal decompression in the patients with front-orbital fibrous dysplasia and the methods of intraoperative optic canal localization and decompression. Methods We collected 30 cases of fibrous dysplasia. All patients had sufficient images assessment. Patients with symptoms underwent surgery, including front-orbital cranioplasty and optic canal decompression. The frontotemporal epidural approaches were used. If there was a proptosis, the approach was extended with the removal of superior orbital ridge. Six patients undertook intraoperative CT and MRI fusion navigation, assisting in confirming the trunk, orbital and cranial orifice of optic nerve. During the operation, the optic canals were decompressed by three-bits method, to confirm the position of optic nerve. Results There were 30 cases of optic canal decompression and one case of vision loss. The visual acuity and vision field of the remaining patients improved to varying degrees. The proptosis disappeared or alleviated after the operation. Thirteen cases were reconstructed with normal internal plate, five cases with titanium plate, nine cases without reconstruction, and two cases were paved with proliferative broken bone on the orbital top; one case recurred with exophthalmos again after five years, but the visual acuity did not decline. Conclusion For the patients with front-orbital fibrous dysplasia, active surgical treatment should be taken, optic canal decompression should be chosen for diminution of vision, craniofacial anaplasty and orbital decompression should be performed in patients with facial deformity. The epidural approach is a good option to locate the optic nerve from the orbital orifice or cranial orifice. Combined with the three-bits method, we can achieve safe and meticulous optic nerve decompression.

[ ABSTRACT] AIM:To investigate the molecular mechanism and the immunosuppressive phenotype of macropha-ges under long-term exposure to lipopolysaccharide ( LPS) .METHODS:We used Ficoll-Hypaque density gradient centri-fugation combined with MicroBeads Separation Kits to separate peripheral blood mononuclear cells from human blood, and then induced the monocytes into macrophages.We observed the morphology of the macrophages by treating the cells with LPS for 48 h, in comparison with a negative control and IFN-γtreatment.ELISA was used to detect the levels of cytokines, such as IL-10, IL-12, IL-6 and TNF-α, and flow cytometry was used to detect the expression of the surface molecules (HLA-DR, CD14, CCR7, HLA-ABC and CD40).To observe the effect of macrophage on T cell proliferation, co-culture experiment was carried out for 6 d.Real-time PCR was used to validate the expression levels of molecules related to MyD88-independent pathway in Toll-like receptor 4 ( TLR4) signal pathway.RESULTS:The antigen-presenting ability of the macrophages was reduced and the IL-10 expression level was increased after the cells were treated with LPS for 48 h. We observed a poor proliferative capacity of CD8 +T cells after co-culturing of LPS-induced macrophages with CD3+T cells for 6 d.The results of real-time PCR indicated that TRIF, IRF3 and CIITA were down-regulated in LPS-induced macropha-ges.CONCLUSION:We successfully established a macrophage model in vitro and observed that LPS-induced macropha-ges into an immunosuppressive phenotype with poor CD8 +T cell proliferative capacity, in which MyD88-independent TLR4 signaling pathway was impaired.

AIM:To identify and analyze tyrosine-phosphorylated proteins regulated by protein tyrosine phos-phatase-like A domain containing protein 1 ( PTPLAD1) in colon cancer cells by phosphoproteomics.METHODS: The expression of PTPLAD1 in colon cancer cell line HCT-116 was knocked down by small interfering RNAs, and the differenti-al expression of tyrosine-phosphorylated proteins in response to the konckdown of PTPLAD1 in HCT-116 cells was identified by stable isotope labeling with amino acid in cell culture ( SILAC) , coupled with the tyrosine phosphorylation antibody im-munoprecipitation and LC-MS/MS analysis.The Ingenuity Pathway Analysis ( IPA) software was employed for bioinformat-ics analysis on the differentially-expressed proteins.RESULTS:A total of 20 differentially-expressed tyrosine-phosphoryla-ted proteins were identified by MS, including 8 markedly up-regulated and 10 evidently down-regulated proteins.IPA soft-ware suggested that these proteins were mainly associated with the disease of cancer, tissue development and function, and cell death and survival.CONCLUSION:We successfully identified PTPLAD1-regulated differentially-expressed tyrosine-phosphorylated proteins in colon cancer cell line HCT-116.Our analysis suggests that PTPLAD1-regulated proteins in colon cancer are closely correlated with colon cancer.

Humans ; Ki-67 Antigen ; metabolism ; Lymphoma, Extranodal NK-T-Cell ; diagnosis ; Predictive Value of Tests ; Prognosis

Objective To explore the value of Golgi protein 73 (GP73 )combined with phosphatidyl alcohol proteoglycans-3 (GPC3 )detection in early diagnosis of primary liver cancer (PLC).Methods The serum GP73 and GPC3 levels were detected in 40 PLC patients,48 patients with liver cirrhosis,45 hepatitis patients and 44 healthy people by ELISA.Results Serum GP73 was (812.37±81.59)pg/mL and GPC3 was(89.27±12.38)ng/mL in PLC group,and GPC3, GP73 positive expression rate were 82.5%,87.5% respectively,which were significantly higher than the other 3 groups.GPC3 and GP73 levels,positive expression rate in liver cirrhosis patients and hepatitis patients were significantly higher than healthy control group.Sensitivity,specific de-grees and accuracy of GPC3 combined with GP73 detection were 92.5%,100% and 93.81%, which were significantly higher than those of GP73 ,GPC3 single test (P<0 .05 ).Conclusion GP73 combined with GPC3 detection can significantly improve the accuracy of PHC,which shows a high value in early diagnosis of PLC.

Objective To explore the value of Golgi protein 73 (GP73 )combined with phosphatidyl alcohol proteoglycans-3 (GPC3 )detection in early diagnosis of primary liver cancer (PLC).Methods The serum GP73 and GPC3 levels were detected in 40 PLC patients,48 patients with liver cirrhosis,45 hepatitis patients and 44 healthy people by ELISA.Results Serum GP73 was (812.37±81.59)pg/mL and GPC3 was(89.27±12.38)ng/mL in PLC group,and GPC3, GP73 positive expression rate were 82.5%,87.5% respectively,which were significantly higher than the other 3 groups.GPC3 and GP73 levels,positive expression rate in liver cirrhosis patients and hepatitis patients were significantly higher than healthy control group.Sensitivity,specific de-grees and accuracy of GPC3 combined with GP73 detection were 92.5%,100% and 93.81%, which were significantly higher than those of GP73 ,GPC3 single test (P<0 .05 ).Conclusion GP73 combined with GPC3 detection can significantly improve the accuracy of PHC,which shows a high value in early diagnosis of PLC.

Objective To improve the operative outcome of parasagittal meningiomas in central area. Methods Twenty patients with parasagittal meningiomas were treated with microsurgery. Of them, 16 cases were taken DSA exzamination before operation to evaluate the blood supplies of the tumor, compensation of venus return around the tumor after obstruction of the sagittal sinus. During the operation, the parasagittal blood supplies were blocked first, the tumors were resected piece by piece. Rolandic veins, other compensative venous pathways and normal brains around the tumors were protected, and the involved sagittal sinuses were appropriately treated. Results Total removal of the tumor was reached in 17 cases, nearly total removal in 3 cases, no death. Postoperatively, 1 patient developed hemiparesis, 2 had paresis of both lower extremities. No tumor recurrence was found in 13 patients during the follow-up of 3～7 years. Conclusion Using microsurgical techniques in the resection of parasagittal meningioma in central area may improve the percentage of total tumor resection, decrease the injuries of important functional area of the brain, reduce complications and improve survival outcome.