Exosomal circRNA_100284 from arsenite-transformed cells, via microRNA-217 regulation of EZH2, is involved in the malignant transformation of human hepatic cells by accelerating the cell cycle and promoting cell proliferation.
Exosomal circRNA_100284 from arsenite-transformed cells, via microRNA-217 regulation of EZH2, is involved in the malignant transformation of human hepatic cells by accelerating the cell cycle and promoting cell proliferation.
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来自亚砷酸盐转化细胞的外泌体circRNA_100284通过microRNA-217调节EZH2，通过加速细胞周期和促进细胞增殖参与人肝细胞的恶性转化。
DOI：
10.1038/s41419-018-0485-1
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发表时间：
2018-05-01
影响因子：
9
通讯作者：
Liu Q
中科院分区：
文献类型：
--
作者：
Dai X;Chen C;Yang Q;Xue J;Chen X;Sun B;Luo F;Liu X;Xiao T;Xu H;Sun Q;Zhang A;Liu Q
恶性细胞和邻近的非恶性细胞之间的细胞间通讯参与癌的发生。在癌变过程中，外来体是细胞间通讯的信使。环状RNA（circRNA）是具有包括调节细胞周期和增殖的功能的非编码RNA。然而，外泌体circRNA的功能尚不清楚。本研究旨在确定从砷转化的人肝上皮（L-02）细胞分泌的circRNA是否转移到正常L-02细胞中并在正常细胞中变得功能活性。结果表明，circRNA_100284参与了砷诱导的L-02细胞恶性转化。转化L-02细胞的培养基诱导circRNA_100284的上调，加速细胞周期，并促进正常L-02细胞的增殖。转化细胞通过外泌体将circRNA_100284转移到正常L-02细胞中，并导致非转化细胞的恶性转化。circRNA_100284的敲低降低了来源于转化的L-02细胞的外来体中的circRNA_100284水平，阻断了加速的细胞周期并降低了增殖和恶性。此外，在正常L-02细胞中，来源于亚砷酸盐转化的L-02细胞的外泌体circRNA_100284通过充当microRNA-217的海绵来诱导细胞周期的加速并促进增殖。此外，外泌体circRNA_100284在暴露于亚砷酸盐的人的血清中上调。因此，来源于转化的L-02细胞的外泌体将circRNA_100284转移到周围细胞，这诱导加速的细胞周期并促进正常肝细胞的增殖，并导致未转化细胞的恶性转化。这些发现支持了这样的概念，即在亚砷酸盐诱导的致癌过程中，外泌体circRNA参与细胞-细胞通讯。
Intercellular communication between malignant cells and neighboring nonmalignant cells is involved in carcinogenesis. In the progression of carcinogenesis, exosomes are messengers for intercellular communication. Circular RNAs (circRNAs) are noncoding RNAs with functions that include regulation of the cell cycle and proliferation. However, the functions of exosomal circRNAs are not clear. The present research aimed to determine whether circRNAs secreted from arsenite-transformed human hepatic epithelial (L-02) cells are transferred into normal L-02 cells and become functionally active in the normal cells. The results showed that circRNA_100284 is involved in the malignant transformation of L-02 cells induced by arsenite. The medium from transformed L-02 cells induced upregulation of circRNA_100284, accelerated the cell cycle, and promoted proliferation of normal L-02 cells. Transformed cells transferred circRNA_100284 into normal L-02 cells via exosomes and led to the malignant transformation of the non-transformed cells. Knockdown of circRNA_100284, which reduced circRNA_100284 levels in exosomes derived from transformed L-02 cells, blocked the accelerated cell cycle and reduced proliferation and malignancy. In addition, in normal L-02 cells, exosomal circRNA_100284 derived from arsenite-transformed L-02 cells induced acceleration of the cell cycle and promoted proliferation via acting as a sponge of microRNA-217. Further, exosomal circRNA_100284 was upregulated in the sera of people exposed to arsenite. Thus, exosomes derived from transformed L-02 cells transferred circRNA_100284 to surrounding cells, which induced an accelerated cell cycle and promoted proliferation of normal liver cells and led to the malignant transformation of the non-transformed cells. The findings support the concept that exosomal circRNAs are involved in cell–cell communication during carcinogenesis induced by arsenite.
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影响因子：
9.7
作者：
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通讯作者：
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影响因子：
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