ZNNT1 long noncoding RNA induces autophagy to inhibit tumorigenesis of uveal melanoma by regulating key autophagy gene expression
ZNNT1 long noncoding RNA induces autophagy to inhibit tumorigenesis of uveal melanoma by regulating key autophagy gene expression
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ZNNT1长非编码RNA诱导自噬通过调节关键自噬基因表达抑制葡萄膜黑色素瘤的肿瘤发生
DOI：
10.1080/15548627.2019.1659614
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发表时间：
2019-09-04
期刊：
影响因子：
13.3
通讯作者：
Fan, Xianqun
中科院分区：
文献类型：
--
作者：
Li, Peng;He, Jie;Fan, Xianqun
长非编码RNA(LncRNAs)被证明是许多细胞过程中的关键调控因子。然而，lncRNAs在宏观自噬/自噬中的潜在参与在很大程度上是未知的。自噬是一种高度调控的细胞降解系统，它的失调与包括癌症在内的许多人类疾病有关。在这里，我们证明了在葡萄膜黑色素瘤(UM)细胞中，lncRNA ZNNT1是由pp242和mTORC1选择性抑制剂雷帕霉素诱导的。ZNNT1的过表达通过上调ATG12的表达来促进自噬，而ZNNT1的敲除则减弱了pp242诱导的自噬。ZNNT1过表达抑制UM细胞的成瘤和迁移，ATG12基因敲除可部分挽救ZNNT1抑制UM成瘤的作用。综上所述，我们的研究表明，ZNNT1通过诱导自噬在UM中发挥潜在的肿瘤抑制作用。
Long noncoding RNAs (lncRNAs) are proved to be critical regulators in numerous cellular processes. However, the potential involvement of lncRNAs in macroautophagy/autophagy is largely unknown. Autophagy is a highly regulated cellular degradation system, and its dysregulation is involved in many human diseases, including cancers. Here, we show that the lncRNA ZNNT1 is induced by PP242 and MTORC1 selective inhibitor rapamycin in uveal melanoma (UM) cells. Overexpression of ZNNT1 promotes autophagy by upregulating ATG12 expression, whereas knockdown of ZNNT1 attenuates PP242-induced autophagy. Overexpression of ZNNT1 inhibits tumorigenesis and the migration of UM cells, and knockdown of ATG12 can partially rescue the ZNNT1-induced inhibition of UM tumorigenesis. In summary, our study reveals that ZNNT1 acts as a potential tumor suppressor in UM by inducing autophagy.