Chimeric RNA ASTN2-PAPPA(as) aggravates tumor progression and metastasis in human esophageal cancer

Lu Wang, Xiao Xiong, Zhimeng Yao, Jianlin Zhu, Yusheng Lin, Wan Lin, Kai Li, Xiaozheng Xu, Yi Guo, Yuping Chen, Yunlong Pan, Fuyou Zhou, Jun Fan, Yan Chen, Shegan Gao*, Sai-Ching Jim Yeung, Hao Zhang

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

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    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-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.

    Original languageEnglish
    Pages (from-to)1-11
    Number of pages11
    JournalCancer letters
    Volume501
    DOIs
    Publication statusPublished - 31-Mar-2021

    Keywords

    • Chimeric RNA
    • Esophageal squamous cell carcinoma
    • Sternness
    • Metastasis
    • PAPP-A
    • PAF1 COMPLEX
    • CELLS
    • OCT4
    • ERK5
    • DIFFERENTIATION
    • TRANSCRIPTION
    • PROTEIN

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