Department of General Surgery, The First Affiliated Hospital of Jinan University, Institute of Precision Cancer Medicine and Pathology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.
Department of General Surgery, The First Affiliated Hospital of Jinan University, Institute of Precision Cancer Medicine and Pathology, School of Medicine, Jinan University, Guangzhou, Guangdong, China; Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Cancer Lett. 2021 Mar 31;501:1-11. doi: 10.1016/j.canlet.2020.10.052. Epub 2020 Dec 31.
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 chimeric RNA (A-PchiRNA) that could be the first reported chimeric RNA derived from the splicing of exons and intron antisense of two neighboring genes, respectively. Aberrant A-PchiRNA level in ESCC tissues was associated with tumor progression and patients' outcome. In vitro and in vivo studies demonstrated that A-PchiRNA aggravated ESCC metastasis and enhanced stemness through modulating OCT4. Mechanistic studies demonstrated that ERK5-mediated non-canonical PAF1 activity was required for A-PchiRNA-induced cancer malignancy. The study defined an undocumented function of chimeric RNAs in aggravating cancer stemness and metastasis.
转录诱导嵌合 RNA 是疾病生物标志物和治疗靶点开发的分子特征研究的一个新兴领域。尽管它们很重要，但对于嵌合 RNA 的相关作用及其在癌症发病机制和进展中的潜在机制知之甚少。在这里，我们描述了一种独特的 ASTN2-PAPPA 嵌合 RNA（A-PchiRNA），它可能是第一个报道的嵌合 RNA，源自两个相邻基因的外显子和内含子反义剪接。ESCC 组织中异常的 A-PchiRNA 水平与肿瘤进展和患者预后相关。体外和体内研究表明，A-PchiRNA 通过调节 OCT4 加重 ESCC 转移并增强干性。机制研究表明，ERK5 介导的非典型 PAF1 活性是 A-PchiRNA 诱导的癌症恶性所必需的。该研究定义了嵌合 RNA 在加重癌症干性和转移中的一个未被记录的功能。
