【摘要】 目的：研究LINC00617对肺癌细胞增殖、凋亡及吉西他滨耐药性的影响及机制。方法：采用不同浓度（2、4、6、8μmol/L）吉西他滨处理肺癌A549和吉西他滨耐药细胞A549-Gem细胞，CCK8法和克隆形成实验检测吉西他滨对A549细胞存活率和克隆形成数，qRT-PCR检测细胞中LINC00617和miR-218的水平，Western blot检测细胞中Ki67和Caspase3表达水平，流式细胞术检测细胞凋亡率，双荧光素酶报告系统验证LINC00617和miR-218的靶向关系。结果：随着吉西他滨（2、4、6、8μmol/L）浓度升高，A549细胞存活率逐渐降低，A549-Gem细胞存活率无显著变化，最高浓度（8μmol/L）吉西他滨时A549-Gem细胞存活率（97.01±7.26）%显著高于A549（43.21±5.35）%;LINC00617在A549-Gem细胞中含量（3.19±0.14）显著高于A549细胞（1.00±0.08）（P<0.05）；抑制LINC00617或过表达miR-218后细胞存活率和克隆形成数均降低，凋亡率升高，增殖蛋白Ki67含量降低，凋亡蛋白Caspase3含量升高，差异均具有统计学意义（P<0.05）;LINC00617靶向负调控miR-218的表达；过表达miR-218增强了抑制LINC00617对A549-Gem细胞增殖、凋亡和吉西他滨耐药性的作用。结论：LINC00617可靶向miR-218调控A549-Gem细胞的增殖、凋亡及吉西他滨耐药性，也是肺癌潜在的分子靶点。更多还原

【Abstract】 Objective:To investigate the effects of LINC00617 on the proliferation, apoptosis and gemcitabine resistance of lung cancer cells and the potential molecular mechanism. Methods:Lung cancer A549 cells and gemcitabine resistant A549-Gem cells were treated with gemcitabine of different concentrations(2, 4, 6, 8 μmol/L). The survival rate and clone formation number of gemcitabine on A549 and A549-Gem cells were detected by CCK8 method and clone formation experiment. The levels of LINC00617and miR-218 in cells were detected by qRT-PCR. Western blot was used to detect the expression levels of Ki67 and Caspase3 in cells, flow cytometry was used to detect the apoptosis rate, and dual luciferase reporting system was performed to examine the targeted relationship between LINC00617 and miR-218. Results:With the increase of gemcitabine(2, 4, 6, 8 μmol/L), the survival rate of A549cells was gradually decreased, but the survival rate of A549-Gem cells was not changed significantly. The survival rate of A549-Gem cells at the highest concentration of 8 μmol/L gemcitabine(97.01±7.26)% was significantly higher than that of A549(43.21±5.35)%.The level of LINC00617 in A549-Gem cells(3.19±0.14) was significantly higher than that in A549 cells(1.00±0.08)(P<0.05). After inhibiting LINC00617 or over-expressing miR-218, the cell survival rate and the number of clones were both decreased, the apoptosis rate was increased, the level of proliferation protein Ki67 was decreased, and the content of apoptosis protein Caspase3 was increased, with statistical significance(P<0.05). LINC00617 targets and negative regulates the expression of miR-218. Over-expression of miR-218 enhanced the effect of LINC00617 inhibition on proliferation, apoptosis and gemcitabine resistance of A549-Gem cells.Conclusion:LINC00617 regulates the proliferation, apoptosis and gemcitabine resistance of A549-Gem cells by targeting miR-218.LINC00617 is a potential molecular target for lung cancer.更多还原