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SNHG9是一种在甲状腺乳头状癌细胞外泌体中富集的长链非编码RNA,它通过YBOX3/P21途径抑制正常甲状腺上皮细胞Nthy-ori-3的细胞自噬并促进其细胞凋亡。

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.

作者信息

Wen Duo, Liu Wan-Lin, Lu Zhong-Wu, Cao Yi-Ming, Ji Qing-Hai, Wei Wen-Jun

机构信息

Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.

Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

出版信息

Front Oncol. 2021 May 4;11:647034. doi: 10.3389/fonc.2021.647034. eCollection 2021.

Abstract

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.

摘要

甲状腺癌是最常见的内分泌恶性肿瘤。尽管总体预后良好,但晚期疾病的治疗仍然具有挑战性。外泌体是包含特定成分的囊泡单位,可在细胞间传递信息。为了探讨其在甲状腺乳头状癌(PTC)中的作用,我们的研究通过lncRNA芯片筛选了外泌体富集的lncRNA SNHG9,并探讨了其生物学功能。我们使用lncRNA芯片结合生物信息学分析来筛选外泌体中富集的lncRNA SNHG9。GO分析表明其与自噬和凋亡有关。定量PCR显示SNHG9在PTC细胞和外泌体中高表达,并通过临床特征分析了其与PTC肿瘤大小的相关性。SNHG9可通过PTC细胞外泌体抑制人正常甲状腺上皮细胞系Nthy-ori-3饥饿诱导的保护性细胞自噬,并促进其凋亡。RNA下拉结合蛋白质谱显示SNHG9可与YBOX3相互作用。蛋白质免疫印迹和RNA免疫沉淀进一步证实了它们的相互作用。蛋白质免疫印迹显示SNHG9可诱导YBOX3降解,从而干扰P21 mRNA的稳定性并诱导细胞凋亡。总之,我们的研究确定SNHG9是一种PTC细胞外泌体富集的lncRNA。SNHG9可通过YBOX3/P21途径抑制细胞自噬并促进Nthy-ori-3细胞凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb64/8129558/0b037cb7295d/fonc-11-647034-g001.jpg

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