SNHG9, a Papillary Thyroid Cancer Cell Exosome-Enriched lncRNA, Inhibits Cell Autophagy and Promotes Cell Apoptosis of Normal Thyroid Epithelial Cell Nthy-ori-3 Through YBOX3/P21 Pathway.

SNHG9, a Papillary Thyroid Cancer Cell Exosome-Enriched lncRNA, Inhibits Cell Autophagy and Promotes Cell Apoptosis of Normal Thyroid Epithelial Cell Nthy-ori-3 Through YBOX3/P21 Pathway.
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SNHG9,一个乳头状甲状腺癌细胞外泌体富集lncRNA,通过YBOX3/P21通路抑制正常甲状腺上皮细胞Nthy-ori-3细胞自噬并促进细胞凋亡

DOI:
10.3389/fonc.2021.647034
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发表时间:
2021
影响因子:
4.7
通讯作者:
Wei WJ
Wei WJ
中科院分区:
医学3区
文献类型:
--
作者:
Wen D;Liu WL;Lu ZW;Cao YM;Ji QH;Wei WJ

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甲状腺癌是最常见的内分泌恶性肿瘤。虽然总体预后良好,但晚期疾病的治疗仍具有挑战性。胞外体是囊泡单位,含有在细胞之间传递信息的特定成分。为了探讨其在甲状腺乳头状癌(PTC)中的作用,本研究利用lncRNA芯片筛选了富含外体的lncRNA SNHG9,并对其生物学功能进行了初步探讨。我们利用lncRNA芯片结合生物信息学分析来筛选富含外切体的lncRNA SNHG9。GO分析提示其与自噬和细胞凋亡有关。定量聚合酶链式反应显示SNHG9在PTC细胞和外切体中高表达,并结合临床特征分析其与PTC肿瘤大小的关系。SNHG9可抑制饥饿诱导的人正常甲状腺上皮细胞株Nthy-Ori-3的保护性细胞自噬,并通过PTC细胞外体促进其凋亡。RNA下拉结合蛋白质谱分析表明SNHG9能与YBOX3相互作用。Western印迹和RNA免疫沉淀进一步证实了它们之间的相互作用。Western印迹结果显示,SNHG9可诱导YBOX3降解,从而干扰P21mRNA的稳定性,诱导细胞凋亡。综上所述,我们的研究证实SNHG9是PTC细胞外切小体富含的lncRNA。SNHG9通过YBOX3/P21途径抑制Nthy-Ori-3细胞自噬,促进细胞凋亡。
Thyroid cancer is the most common type of endocrine malignancy. Although the general prognosis is good, the treatment of advanced disease is still challenging. Exosomes are vesicle units containing specific components that transmit information between cells. In order to explore its role in papillary thyroid cancer (PTC), our study screened exosome enriched lncRNA SNHG9 by lncRNA chip and explored its biological function. We used lncRNA chips combined with bioinformatics analysis to screen lncRNA SNHG9 enriched in exosomes. GO analysis suggested its relationship with autophagy and apoptosis. Quantitative PCR showed SNHG9 was highly expressed in PTC cells and exosomes and its correlation with PTC tumor size was analyzed by clinical characteristics. SNHG9 could inhibit the protective cell autophagy induced by starvation of human normal thyroid epithelial cell line Nthy-ori-3 and promote its apoptosis through PTC cell exosomes. RNA-pull down combined with protein spectrum showed that SNHG9 could interact with YBOX3. Western blot and RNA immunoprecipitation further confirmed their interaction. Western blot showed that SNHG9 could induce degradation of YBOX3, thus interfering with the stability of P21 mRNA and inducing cell apoptosis. In conclusion, our study identified SNHG9 as a PTC cell exosome-enriched lncRNA. SNHG9 could inhibit cell autophagy and promote apoptosis of Nthy-ori-3 cell through YBOX3/P21 pathway.
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