SNORA72 Activates the Notch1/c-Myc Pathway to Promote Stemness Transformation of Ovarian Cancer Cells.
SNORA72 Activates the Notch1/c-Myc Pathway to Promote Stemness Transformation of Ovarian Cancer Cells.
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SNORA72激活Notch1/c-Myc通路促进卵巢癌细胞干细胞转化
DOI：
10.3389/fcell.2020.583087
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发表时间：
2020
影响因子：
5.5
通讯作者：
He M
中科院分区：
文献类型：
--
作者：
Zhang L;Ma R;Gao M;Zhao Y;Lv X;Zhu W;Han L;Su P;Fan Y;Yan Y;Zhao L;Ma H;Wei M;He M
癌症干细胞（CSCs）负责癌症进展的迁移和复发。小核仁rna （Small nucleolar rna, snoRNAs）在肿瘤发生发展中起着重要作用。然而，snorna如何参与卵巢CSCs （OCSCs）的干性调节尚不清楚。在本研究中，我们发现在OVCAR-3 （OV）和CAOV-3 （CA）细胞的悬液中无血清培养获得OCSC特征的OVCAR-3球状体（OS）和CAOV-3球状体（CS）中，SNORA72的表达显著上调。SNORA72的过表达增加了OV和CA细胞的自我更新能力和迁移能力，并上调了干细胞标记物Nanog、Oct4和CD133的表达。此外，异位表达SNORA72可提高亲本细胞Notch1和c-Myc的信使RNA （mRNA）和蛋白表达水平。在snora72沉默的OCSCs中观察到相反的结果。此外，我们发现Notch1敲低可以逆转过表达SNORA72所提高的迁移能力和自我更新能力。综上所述，SNORA72可通过Notch1/c-Myc通路激活卵巢癌细胞的干性转化。本研究为提高卵巢癌的治疗效率提供了一种新的治疗策略。
Cancer stem cells (CSCs) are responsible for the migration and recurrence of cancer progression. Small nucleolar RNAs (snoRNAs) play important roles in tumor development. However, how snoRNAs contribute to the regulation of the stemness of ovarian CSCs (OCSCs) remains unclear. In the present study, we found that SNORA72 was significantly upregulated in OVCAR-3 spheroids (OS) and CAOV-3 spheroids (CS) with the OCSC characteristics attained by serum-free culture in a suspension of OVCAR-3 (OV) and CAOV-3 (CA) cells. The overexpression of SNORA72 increased self-renewal abilities and migration abilities in OV and CA cells and upregulated the expressions of the stemness markers Nanog, Oct4, and CD133. In addition, the ectopic expression of SNORA72 can elevate the messenger RNA (mRNA) and protein expression levels of Notch1 and c-Myc in parental cells. The opposite results were observed in SNORA72-silenced OCSCs. Moreover, we found that Notch1 knockdown inversed the migration abilities and self-renewal abilities raised by overexpressing SNORA72. In summary, stemness transformation of ovarian cancer cells can be activated by SNORA72 through the Notch1/c-Myc pathway. This study introduces a novel therapeutic strategy for improving the treatment efficiency of ovarian cancer.