A novel antitumor peptide inhibits proliferation and migration and promotes apoptosis in glioma cells by regulating the MKK6/p38 signaling pathway.

Protein- or peptide-based therapeutics have emerged as an innovative strategy for the treatment of cancer. Our previous research demonstrated that tripartite motif 9 short isoform (TRIM9s) is a tumor suppressor in glioma. In this report, we investigated whether a new peptide derived from TRIM9s, named T9sP, inhibits glioma progression and determined the possible molecular mechanism. The CCK-8 proliferation assay was performed in LN229 and U251 glioma cells. The scratch-wound assay was used to determine the migration of the cells. Apoptosis was assessed by flow cytometry using Annexin V-FITC/PI double staining method. The relative protein expression levels were detected by immunoblot analysis. The cell-penetrating peptide TAT was fused with T9sP to form TAT-T9sP. TAT-T9sP efficiently penetrated through the cell membrane of both LN229 and U251 cells. TAT-T9sP inhibited proliferation and migration and promoted apoptosis of glioma cells. TAT-T9sP activated p38 signaling by upregulating MKK6, and a p38 inhibitor, SB203580, reversed the inhibitory effects of TAT-T9sP on glioma cells. These results indicated the potential of TAT-T9sP for the development of a new anti-glioma medicine.

MicroRNA-29a-3p Downregulation Causes Gab1 Upregulation to Promote Glioma Cell Proliferation.

BACKGROUND/AIMS: Glioma causes significant human mortalities annually. Molecularly-targeted therapy is a focus of glioma research. METHODS: Grb2-associated binding 1 (Gab1) expression and microRNA-29a-3p ("miR-29a-3p") expression in human glioma cells and tissues were tested by Western blotting assay and qRT-PCR assay. shRNA/siRNA strategy was applied to silence Gab1 in human glioma cells. miR-29a or anti-sense miR-29a construct was transfected to human glioma cells. Cell proliferation was tested by BrdU ELISA assay and cell counting assay. RESULTS: We show that expression of Gab1 was significantly elevated in human glioma tissues and cells, which correlated with downregulation of its putative microRNA: miR-29a-3p. In A172 glioma cells and primary human glioma cells, Gab1 shRNA/siRNA inhibited Akt-Erk activation and cell proliferation. Forced-expression of miR-29a-3p downregulated Gab1, inhibiting glioma cell proliferation, whereas miR-29a-3p was in-effective on cell proliferation in Gab1-silenced A172 cells. Furthermore, introduction of a 3'-untranslated region (3'-UTR) mutant Gab1 (UTR-G160A) blocked miR-29a-3p-induced inhibition on Akt signaling and A172 cell proliferation. CONCLUSIONS: miR-29a-3p downregulation leads to Gab1 upregulation to promote glioma cell proliferation.

[Establishment of malignant progression associated gene expression profiles in human brain glioma].

OBJECTIVE: To establish malignant progression associated gene expression profiles in human brain glioma. METHODS: The primary (WHO grade II), recurrent (WHO grade III) and re-recurrent (WHO grade IV) glioma specimens were sequentially collected from one single patient. Gene expression of different tumor specimens and normal brain tissue of the same patient was compared by microarrary techniques. RESULTS: 197 differentially expressed genes with differential ratio > or = 3 were observed when compared with normal brain tissue. When the specimens (3 tumor, 1 normal brain) were paired with each other, 7 groups containing 489 genes (upregulated 193, downregulated 296) were observed. According to the descending frequency of the 109 genes with known function, they were the genes associated with development, metabolism, differentiation, signal transduction, DNA binding transcription, cellular receptor, immunity, ion-channel transportation, protein translation, cell backbone motion, stress, protooncogene and anti-oncogene and cell apoptosis, respectively. CONCLUSION: From the 197 differentially expressed genes found in one glioma patient experiencing tumor malignant progression, 17 genes screened out by bioinformatics assay, may offer valuable information on molecular mechanisms on genesis and malignant progression of glioma.

[Bioinformatic analysis of glioma development relative genes].

BACKGROUND & OBJECTIVE: Exploiting the transcriptional regulation mechanism by microarray and bioinformatics is an important method at genomic research field, and it is better than previous methods, by which we can easily analyze the gene expression regulative networks at genomic level. This study was designed to analyze the glioma gene expression profiles by clustering and bioinformatic retrieving to seek some tumor development relative genes that can be cloned for the purpose of function research in the future. METHODS: Firstly, we analyzed the glioma gene expression profiles of 16,363 genes by clustering, and chose 368 genes which expression differences were greater than 2 folds and the variances of 2 dots were smaller than 0.33. We selected 2 groups of genes that were expressed similarly. One group (11 cases) was upregulated with the glioma development and another (6 cases) was downregulated with the glioma development. Secondly, we determined the genomic information about those 17 genes and exploited their association with the development of gliomas. RESULTS: Two groups of genes were expressed similarly during the glioma development, one group was upregulated with the development of gliomas, and another was downregulated. Bioinformatic analysis showed that 3 of those genes (X55987, M85085, and AB011097) might be important tumor relative genes. CONCLUSION: By bioinformatics and microarray technologies, we found 3 genes, X55987(EDN, eosinophil-derived neurotoxin), AB011097 (ARTS-1, TNF receptor shedding regulator),and M85085(CStF, cleavage stimulation factor), which might be potential key tumor development relative genes that can be developed for therapy targets in the future.