Chimeric RNA ASTN2-PAPPAas aggravates tumor progression and metastasis in human esophageal cancer
Chimeric RNA ASTN2-PAPPAas aggravates tumor progression and metastasis in human esophageal cancer
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嵌合 RNA ASTN2-PAPPAas 会加剧人食管癌的肿瘤进展和转移。
DOI：
10.1016/j.canlet.2020.10.052
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发表时间：
2021-01-04
期刊：
影响因子：
9.7
通讯作者：
Zhang, Hao
中科院分区：
文献类型：
--
作者：
Wang, Lu;Xiong, Xiao;Zhang, Hao
转录诱导的嵌合RNA是研究疾病生物标志物和治疗靶点开发的分子特征的新兴领域。尽管它们的重要性，嵌合RNA相关的作用和癌症发病机制和进展的潜在机制知之甚少。在这里，我们描述了一个独特的ASTN 2-PAPPA（反义）嵌合RNA（A-P-作为chiRNA），这可能是第一个报告的嵌合RNA来自剪接的外显子和内含子反义的两个相邻的基因，分别。ESCC组织中A-P-as chiRNA水平异常与肿瘤进展和患者结局相关。体外和体内研究表明，A-P-as chiRNA通过调节OCT 4而加重ESCC转移并增强干性。机制研究表明，ERK 5介导的非经典PAF 1活性是A-P-as chiRNA诱导的癌症恶性所必需的。该研究确定了嵌合RNA在加重癌症干化和转移中的未记录功能。
Transcription-induced chimeric RNAs are an emerging area of research into molecular signatures for disease biomarker and therapeutic target development. Despite their importance, little is known for chimeric RNAs-relevant roles and the underlying mechanisms for cancer pathogenesis and progression. Here we describe a unique ASTN2-PAPPA(antisense) chimeric RNA (A-P-as chiRNA) that could be the first reported chimeric RNA derived from the splicing of exons and intron antisense of two neighboring genes, respectively. Aberrant A-P-as chiRNA level in ESCC tissues was associated with tumor progression and patients' outcome. In vitro and in vivo studies demonstrated that A-P-as chiRNA aggravated ESCC metastasis and enhanced stemness through modulating OCT4. Mechanistic studies demonstrated that ERK5-mediated non-canonical PAF1 activity was required for A-P-as chiRNA-induced cancer malignancy. The study defined an undocumented function of chimeric RNAs in aggravating cancer stemness and metastasis.