Chimeric RNA ASTN2-PAPPAas aggravates tumor progression and metastasis in human esophageal cancer
Lu Wang, Xiao Xiong, Zhimeng Yao, Jianlin Zhu, Yusheng Lin, Wan‐Wan Lin, Kai Li, Xiaozheng Xu, Yi Guo, Yuping Chen, Yunlong Pan, Fuyou Zhou, Jun Fan, Yan Chen, Shegan Gao, Sai‐Ching J. Yeung, Hao Zhang
Abstract
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-PAPPAantisense chimeric RNA (A-PaschiRNA) that could be the first reported chimeric RNA derived from the splicing of exons and intron antisense of two neighboring genes, respectively. Aberrant A-PaschiRNA level in ESCC tissues was associated with tumor progression and patients’ outcome. In vitro and in vivo studies demonstrated that A-PaschiRNA aggravated ESCC metastasis and enhanced stemness through modulating OCT4. Mechanistic studies demonstrated that ERK5-mediated non-canonical PAF1 activity was required for A-PaschiRNA-induced cancer malignancy. The study defined an undocumented function of chimeric RNAs in aggravating cancer stemness and metastasis.