[目的]探讨乏氧条件下长链非编码RNA LINC00488通过miR-376a-3p/AGO2调控甲状腺乳头状癌细胞凋亡的潜在机制.[方法]乏氧处理后,高通量测序和过表达筛选影响乏氧条件下甲状腺乳头状癌细胞B-CPAP凋亡水平的长链非编码RNA.过表达或敲低LINC00488、miR-376a-3p、AG02后检测B-CPAP的凋亡水平.[结果]乏氧条件下,LINC00488的表达水平显著上升.敲低LINC0488后乏氧条件下B-CPAP细胞的凋亡水平显著上升[(24.59±3.55 vs 65.69±8.99)％,P＜0.05].过表达miR-376a-3p后乏氧条件下B-CPAP细胞的凋亡水平显著上升[(25.56±3.86 vs 69.04±9.52)％,P＜0.05].此外,LINC00488和miR-376a-3p存在碱基间的相互作用.敲低AG02后乏氧条件下B-CPAP细胞的凋亡水平显著上升[(26.91±3.77 vs 60.72±8.45)％,P＜0.05].同时,miR-376a-3p靶向结合AGO2 mRNA的3'端非翻译区.过表达miR-376a-3p后乏氧条件下B-CPAP细胞中AG02的mRNA和蛋白水平均下降(0.84±0.18 vs0.11±0.01,P＜0.05);敲低 miR-376a-3p 后乏氧条件下 B-CPAP 细胞中 AG02 的 mR-NA和蛋白水平均上升(0.84±0.18vs 1.43±0.23,P＜0.05).[结论]乏氧条件下,长链非编码RNA LINC00488结合miR-376a-3p后抑制了 miR-376a-3p调节下游基因AG02表达的能力,从而抑制了甲状腺乳头状癌细胞的凋亡.
LINC00488/miR-376a-3p/AGO2 regulates apoptosis of thyroid papillary cancer cells
[Objective]To investigate the potential mechanism of long-stranded non-coding RNA LINC00488 regulating ap-optosis through miR-376a-3p/AGO2 in papillary thyroid carcinoma cells under hypoxic conditions.[Method]High-throughput sequencing and overexpression screening of long-stranded non-coding RNAs affecting the apoptosis level of B-CPAP in papillary thyroid cells under hypoxic treatment.[Result]The expression level of LINC00488 increased significantly under hypoxic conditions.After LINC00488 was knocked down,the apoptosis level of B-CPAP cells was significantly increased under hypoxic conditions[(24.59±3.55 vs 65.69±8.99)％,P＜0.05].After overexpression of miR-376a-3p,the apop-tosis level of B-CPAP cells was significantly increased under hypoxic conditions[(25.56±3.86 vs 69.04±9.52)％,P＜0.05].In addition,there was a base-to-base interaction between LINC00488 and miR-376a-3p.The apoptosis level of B-CPAP cells was significantly increased under hypoxic conditions after AGO2 was knocked down[(26.91±3.77 vs 60.72±8.45)％,P＜0.05].Meanwhile,miR-376a-3p targets the untranslated region of the 3'end of AGO2 mRNA.After overex-pression of miR-376a-3p,mRNA and protein levels of AGO2 in B-CPAP cells were decreased under hypoxic conditions(0.84±0.18 vs 0.11±0.01,P＜0.05).After miR-376a-3p knockdown,the mRNA and protein levels of AGO2 in B-CPAP cells were increased under hypoxic conditions(0.84±0.18 vs 1.43±0.23,P＜0.05).[Conclusion]Under hypoxic conditions,the binding of long non-coding RNA LINC00488 to miR-376a-3p inhibited the ability of miR-376a-3p to regulate the expression of downstream gene AGO2.The apoptosis of thyroid papillary carcinoma cells was inhibited.
LINC00488miR-376a-3pAGO2papillary thyroid carcinomaapoptosishypoxianon-coding RNAthy-roid cancer
万方数据
维普
