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Cell Death Dis:lncRNA DOCK9-AS2促进甲状腺乳头状癌的发生发展

2020-09-17 QQY MedSci原创

甲状腺乳头状癌(PTC)约占甲状腺癌(TC)总病例的80%。目前,PTC的治疗效果总体上令人满意,且超过95%的PTC患者在治疗后可以生存超过5年。但是,仍有约15%的PTC病例表现出侵袭性和不良预后

甲状腺乳头状癌(PTC)约占甲状腺癌(TC)总病例的80%。目前,PTC的治疗效果总体上令人满意,且超过95%的PTC患者在治疗后可以生存超过5年。但是,仍有约15%的PTC病例表现出侵袭性和不良预后。因此仍需改善PTC的诊断和靶向治疗策略。

目前的研究证实,长非编码RNA(lncRNA)能够介导肿瘤微环境中的细胞间通讯。 DOCK9-AS2是一种外泌体lncRNA,GEPIA和circlncRNAnet数据库中显示在甲状腺癌样本中DOCK9-AS2的表达水平上调,但尚无研究报道DOCK9-AS2在PTC中的功能和调节机制。


该研究通过生物信息学数据库分析PTC中差异表达的lncRNA,研究人员发现DOCK9-AS2在PTC中表达上调,且在PTC患者的血浆外泌体中含量升高。功能研究显示,敲低DOCK9-AS2可降低PTC细胞的增殖、迁移、侵袭、上皮-间质转化(EMT)和干细胞特性。研究人员进一步发现PTC肿瘤干细胞(PTC-CSC)能够通过外泌体呈递DOCK9-AS2来改善PTC细胞的干性。

机制研究显示,DOCK9-AS2能与SP1相互作用并诱导CTNNB1(连环蛋白β1)转录,且能够充当miR-1972的分子海绵上调CTNNB1的表达水平,从而激活PTC细胞中的Wnt/β-catenin信号通路。


总而言之,该研究揭示了PTC-CSC外泌体中的lncRNA DOCK9-AS2能够激活Wnt/β-catenin信号通路,并促进甲状腺乳头状癌的发生发展,说明DOCK9-AS2是PTC的一个潜在治疗靶标。


原始出处:

Dai, W., Jin, X., Han, L. et al. Exosomal lncRNA DOCK9-AS2 derived from cancer stem cell-like cells activated Wnt/β-catenin pathway to aggravate stemness, proliferation, migration, and invasion in papillary thyroid carcinoma. Cell Death Dis 11, 743 (11 September 2020).

 

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    2021-04-08 爆笑小医
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    2020-09-18 xzw113
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    2020-09-18 cy0328

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