目的：探讨长链非编码RNA（lncRNA）LINC01410对胶质瘤A172细胞增殖、凋亡和替莫唑胺（temozolomide, TMZ）敏 感性的影响及其机制。方法: 用qPCR法检测胶质瘤细胞系H4、SHG-44、A172和正常星形胶质细胞HA1800中LINC01410表达 水平。将LINC01410 shRNA、shRNA control和miR-205-5p 抑制剂（inhibitor）、inhibitor control转染至A172细胞，MTT法、流式细 胞术分别检测400 μmol/L TMZ处理后，转染细胞的增殖活性和凋亡水平，WB法检测细胞中Bax、Bcl-2、cyclin D1、p27的表达。 在线生物信息学软件LncBase分析LINC01410的靶基因，双荧光素酶报告基因实验验证LINC01410与miR-205-5p的靶向关系。 结果: LINC01410在3种胶质瘤细胞中的表达水平均显著高于正常星形胶质细胞HA1800（均P<0.01），以在A172细胞中的表达 水平最高（P<0.01）。转染LINC01410 shRNA和TMZ 处理后 ，A172 细胞的增殖能力下降、G1 期细胞比例和凋亡率均升高 （均 P<0.01），细胞中 Bax、p27 表达水平升高而 Bcl-2、cyclin D1 表达水平下降（均P<0.01）。双荧光素酶报告基因实验证实 LINC01410 靶向结合 miR-205-5p，下调 LINC01410 促进 miR-205-5p 表达。转染 miR-205-5p 抑制剂可逆转下调 LINC01410 和 TMZ处理对A172细胞增殖、周期和凋亡的影响。结论: 下调lncRNA LINC01410可抑制胶质瘤A172细胞增殖、阻滞细胞周期、 诱导细胞凋亡且提高对TMZ敏感性，其发生机制似与LINC01410对miR-205-5p的靶向作用有关。

Objective: To investigate the effect of lncRNA LINC01410 on the proliferation, apoptosis and temozolomide (TMZ) sensitivity of glioma A172 cells and the underlying mechanism. Methods: qPCR method was used to determine the expression of LINC01410 in glioma cell lines (H4, SHG-44, A172) and normal astrocytes (HA1800). LINC01410 shRNA, shRNA control and miR-205-5p inhibitor and inhibitor control were respectively transfected into A172 cells, which were then treated with 400 μmol/L TMZ. Then, MTT assay and Flow cytometry were used to detect proliferation and apoptosis, and WB was used to detect protein expression of Bax, Bcl-2, cyclin D1 and p27 in transfected A172 cells. The target gene of LINC01410 was predicted by the online bioinformatic software LncBase, and the Dual-luciferase reporter gene system was used to verify the targeting relationship between LINC01410 and miR-205-5p. Results: The expression level of LINC01410 in three glioma cells was higher than that in normal astrocytes HA1800 cells (all P <0.01) with the highest expression level in A172 cells (P<0.01). After LINC01410 shRNA transfection and TMZ treatment, the proliferation decreased while the apoptosis rate increased in A172 cells, and the proportion of cells at G1 phase increased (all P<0.01); moreover, the protein expression level of Bax and p27 increased (all P<0.01), and the expression level of Bcl-2 and cyclin D1 decreased in A172 cells (all P<0.01). Dual-luciferase reporter gene assay verified that LINC01410 could targetedly bind with miR-205-5p, and down-regulation of LINC01410 promoted miR-205-5p expression. Transfection of miR-205-5p inhibitor could reverse the effects of down-regulation of LINC01410 and TMZ treatment on the proliferation, cell cycle and apoptosis of A172 cells. Conclusion: Down-regulation of lncRNA LINC01410 can inhibit proliferation, block cell cycle, induce cell apoptosis, and improve TMZ sensitivity of glioma A172 cells, the mechanism of which may be related with its targeted regulation of miR-205-5p.

河北省卫生厅科研基金资助项目（No.20201493）