摘要:目的探究microRNA-203-5p(miR-203-5p)靶向調(diào)控H編碼人表皮生長因子受體4的癌基因(oncogene encoding human epidermal growth factor receptor 4,ERBB4)對(duì)子宮內(nèi)膜癌小鼠細(xì)胞凋亡的影響和作用機(jī)制。方法隨機(jī)選取18只SPF級(jí)雄性C57/BL6小鼠,依據(jù)隨機(jī)數(shù)字表法將其分為常規(guī)組和模型組,構(gòu)建子宮內(nèi)膜癌小鼠模型;TargetScan預(yù)測miR-203-5p靶基因;構(gòu)建ERBB4的siRNA表達(dá)載體;免疫組化檢測ERBB4表達(dá)情況;將傳代培養(yǎng)后取對(duì)數(shù)期細(xì)胞用于實(shí)驗(yàn),將細(xì)胞分為Blank組、Negative control (NC)組、miR-203-5p mimic組、miR-203-5p inhibitor組、si-ERBB4組、miR-203-5p mimic+si-ERBB4組;采用MTT法測定各組細(xì)胞的增殖情況;采用流式細(xì)胞術(shù)檢測各組細(xì)胞凋亡情況;采用RT-PCR法和western blot法測定相關(guān)mRNA和蛋白表達(dá)量。結(jié)果 miR-203-5p靶向ERBB4;miR-203-5p在子宮內(nèi)膜癌小鼠子宮內(nèi)膜組織中為低表達(dá),ERBB4為高表達(dá);與Blank組相比,miR-203-5p mimic+si-ERBB4組細(xì)胞凋亡率上升且增殖明顯抑制,miR-203-5p inhibitor組結(jié)果相反;與Blank組相比,miR-203-5p表達(dá)在miR-203-5p mimic組和miR-203-5p mimic+si-ERBB4組中上升,在miR-203-5p inhibitor組中結(jié)果相反;與Blank組相比,在miR-203-5p inhibitor組中bcl-2表達(dá)上升而bax、Caspase-3下降,在miR-203-5p mimic組、si-ERBB4組和miR-203-5p mimic+si-ERBB4組中結(jié)果相反;與Blank組相比,ERBB4 mRNA及蛋白表達(dá)在miR-203-5p mimic組、si-ERBB4組和miR-203-5p mimic+si-ERBB4組下降。結(jié)論 miR-203-5p在子宮內(nèi)膜癌小鼠子宮內(nèi)膜組織中低表達(dá),ERBB4高表達(dá)。誘導(dǎo)miR-203-5p表達(dá),可以通過靶向下調(diào)ERBB4基因,上調(diào)bax、Caspase-3表達(dá)并下調(diào)bcl-2表達(dá),從而抑制其細(xì)胞侵襲,誘導(dǎo)其發(fā)生凋亡。
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