microRNA-17-92对人套细胞淋巴瘤细胞放射敏感性的影响

Radiosensitization of microRNA-17-92 on human mantle cell lymphoma cells in vitro

目的 探讨microRNA-17-92对人套细胞淋巴瘤细胞放射敏感性的影响.方法 通过细胞转染获得Z138c-TMP2细胞株和稳定高表达miR-17-92的Z138c-TMP2-miR-17-92细胞株.采用锥虫蓝染色活细胞计数和3H-TdR掺入方法,观察两组细胞外照射后生长情况.采用流式细胞仪检测两组细胞照射后周期时相分布和细胞晚期死亡率.结果 随着照射剂量的增加,miR-17-92组较TMP2组有更多存活细胞（t=-3.12和-3.28,P＜0.05）;TMP2组细胞出现G2/M期阻滞,miR-17-92组未出现明显周期阻滞（t=2.885,P＜0.05）.2和4 Gy照射后培养96 h以上,TMP2组细胞PI单染阳性细胞百分比（24.02%和36.16%）明显高于miR-17-92组（6.49%和11.39%）,差异有统计学意义（t=-17.59、-4.972,P＜0.05）.结论 miR-17-92高表达可明显降低人套细胞淋巴瘤细胞株Z138c细胞的放射敏感性.改变细胞周期和抵抗照射诱导的凋亡是miR-17-92发挥作用途径之一.

Objective To investigate the effects of microRNA-17-92 on radiosensitivity of human mantle cell lymphoma cells. Methods Tetracycline-regulated pRevTet-On expression system was established to generate cell line Z138c-miR-17-92 with over-expressed miR-17-92 and cell line Z138c-TMP2. Cell proliferation was measured by 3 H-TdR incorporation and viable cell counting stained with typan blue. Cell cycle distribution was analysed by flow cytometry（FCM）. Results More viable and proliferous cells were counted in group miR-17-92,when exposure dose was greater than 2 Gy and incubation time was longer than 48 h under the same condition （t = -3. 12 and -3.28,P ＜0. 05）. The percentage of G2/M cells in group TMP2 was increased while no obvious cell cycle arrests were found in group miR-17-92 at 2 and 4 Gy （t = 2. 885, P ＜ 0.05 ）. When cells were incubated for 96 h, higher percentage of propidium iodide （PI） positively stained cells were found in group TMP2 （24. 02% vs. 36. 16% ）compared with group miR-17-92 （6.49% vs. 11.39% ） at 2 and 4 Gy, respectively（ t = - 17.59, - 4. 972, P ＜ 0.05 ）.Conclusions Overexpression of microRNA-17-92 decreased the radiosensitivity of human mantle cell lymphoma cells by inhibition of cell cycle changes and cell apoptosis.