MiR-101-3p inhibits EMT to attenuate proliferation and metastasis in glioblastoma by targeting TRIM44.

BACKGROUND: Glioblastoma (GBM) is the most common malignant tumor originating in the brain parenchyma. The invasive and infiltrative properties of glioblastoma result in poor clinical prognosis to conventional therapies. Emerging reports on microRNAs as important regulators during the process of EMT provide new insights into treating glioblastoma through new targets. However, underlying molecular mechanism of the regulation of miR-101-3p in glioblastoma remains unclear. METHODS: Level of miR-101-3p was determined in GBM cell lines by qRT-PCR. MTT, colony formation and transwell assays were utilized to evaluate functions of overexpression of miR-101-3p/knock down of TRIM44 on proliferation, migration and invasion in GBM cells. Direct interaction between miR-101-3p and TRIM44 was validated using dual luciferase reporter system and impacts of overexpression of miR-101-3p/knock down of TRIM44 on regulation of EMT markers were assessed by Western blotting. RESULTS: MiR-101-3p was validated to be repressed expressed in glioblastoma cancer cell lines. Both overexpression of miR-101-3p and knock down of TRIM44 attenuated proliferation, migration and invasion of glioblastoma cell lines in vitro. TRIM44 was shown to promote EMT in GBM progress and reverse inhibitory function of miR-101-3p. MiR-101-3p was found to suppress the expression of TRIM44 via directly targeting its 3'UTR. CONCLUSIONS: Our findings suggested miR-101-3p regulated proliferation and migration of glioblastoma cells through attenuating TRIM44 induced EMT via direct targeting 3'UTR of TRIM44, which provided preliminary study of potential therapeutic target in future GBM treatment.

Triosephosphate isomerase and peroxiredoxin 6, two novel serum markers for human lung squamous cell carcinoma.

There is currently substantial interest in the identification of human tumor antigens for the diagnosis and immunotherapy of cancer. In our previous study, secretion character and up-regulation of triosephosphate isomerase were observed in lung squamous cell carcinoma, and autoantibodies against triosephosphate isomerase and peroxiredoxin 6 were detected in the sera from over 25% of patients, but in none of the healthy controls. In this study, peroxiredoxin 6 was also found at higher levels in the sera of the patients. Up-regulated triosephosphate isomerase and peroxiredoxin 6 were further validated by enzyme-linked immunosorbent assay in an additional 61 lung squamous cell carcinoma patients, 23 lung adenocarcinoma patients, 56 other types of carcinoma patients, 12 benign lung disease patients, and 59 healthy controls. We found that both triosephosphate isomerase and peroxiredoxin 6 were specifically elevated in lung squamous cell carcinoma sera compared with other groups, with the exception of peroxiredoxin 6 in lung adenocarcinoma patients. Positive correlation between triosephosphate isomerase and distant metastasis was found. At the cut-off point 0.221 (optical density value) on the receiver operating characteristic curve, triosephosphate isomerase could comparatively discriminate lung squamous cell carcinoma from healthy controls with a sensitivity of 65.6%, specificity 84.7%, and total accuracy 75%. For peroxiredoxin 6, at the cut-off point 0.151, it could discriminate the two groups with a sensitivity of 70.5%, specificity 62.7%, and total accuracy 65.8%. With both triosephosphate isomerase and peroxiredoxin 6, discriminant analysis results showed that 68.9% of the lung squamous cell carcinoma and 83.1% of healthy controls were correctly classified. We concluded that triosephosphate isomerase and peroxiredoxin 6 could be markers for lung squamous cell carcinoma.