Expression of long non-coding RNA MTHFD2 and its biological role in human glioblastoma / 医学研究生学报

ABSTRACT

Objective The long non-coding RNA (lncRNA) MTHFD2 gene is expressed differentially in glioblastoma (GBM) and normal brain tissues, but its biological role in tumors, and particularly in GBM, remains unclear. This study aims to investigate the expression of lncRNA MTHFD2 in the GBM tissue and four GBM cell lines, and explore the effect of its down-regulated expression on the biological function of GBM cells. Methods Specimens of GBM and the paracancerous tissue (as normal control) were collected from 9 patients treated by surgical resection in our Department of Neurosurgery between September and December 2017 LV-MTHFD2-shRNA (U251 shRNA and U-87MG shRNA groups) and empty LV-control solution (U251 shRNA and U-87MG control groups) were transfected into the U251 and U-87MG cell lines. The expressions of lncRNA MTHFD2 in the GBM tissue and the GBM cell lines were detected by qRT-PCR, the chemosensitivity and proliferation of the cells after transfection measured by CCK-8 assay, and the changes in the cell migration ability determined by Transwell assay. Results The relative expression of lncRNA MTHFD2 was significantly higher in the GBM than in the normal tissue (5.13 ± 3.96 vs 1.27 ± 0.58, P < 0.05), while that of MTHFD2 was remarkably lower in the U251 shRNA than in the U251 control group (0.05 ± 0.01 vs 1.00 ± 0.00, P < 0.01), and so was that in the U-87MG shRNA than in the U-87MG control (P < 0.05). The number of cells penetrating the Transwell membrane was markedly lower in the U251 shRNA group than in the U251 control (41.4 ± 6.99 vs 125.8 ± 25.27 per field of view, P < 0.01), and so was that in the U-87MG shRNA than in the U-87MG control (P < 0.05). CCK-8 assay showed that, at 4 days after transfection, the A value was significantly decreased in the U251 shRNA and U-87MG shRNA groups as compared with the U251 control and U-87MG control groups (P < 0.05). Cellular drug resistance test manifested remarkably reduced fifty percent inhibitory concentrations (IC50) in the U251 shRNA and U-87MG shRNA groups as compared with the U251 control and U-87MG control groups (P < 0.05). Conclusion DDown-regulation of the expression of lncRNA MTHFD2 can inhibit the proliferation and migration of U251 and U-87MG cells and enhance the chemosensitivity of the cells to temozolomide, which suggests that lncRNA MTHFD2 could be a potential therapeutic target against GBM.