Chimeric RNA ASTN2-PAPPAas 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

doi:10.1016/j.canlet.2020.10.052

Chimeric RNA ASTN2-PAPPA_as aggravates tumor progression and metastasis in human esophageal cancer

Cancer Lett. 2021 Mar 31:501:1-11. doi: 10.1016/j.canlet.2020.10.052. Epub 2020 Dec 31.

Authors

Lu Wang¹, Xiao Xiong¹, Zhimeng Yao¹, Jianlin Zhu¹, Yusheng Lin², Wan Lin³, Kai Li¹, Xiaozheng Xu⁴, Yi Guo⁵, Yuping Chen⁶, Yunlong Pan¹, Fuyou Zhou⁷, Jun Fan⁸, Yan Chen⁸, Shegan Gao⁹, Sai-Ching Jim Yeung¹⁰, Hao Zhang¹¹

Affiliations

¹ 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.
² 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.
³ Cancer Research Center, Shantou University Medical College, Shantou, Guangdong, 515041, China.
⁴ Division of Biological Sciences, University of California San Diego, La Jolla, CA, USA.
⁵ Endoscopy Center, Affiliated Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
⁶ Department of Thoracic Surgery, Affiliated Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
⁷ The Fourth Affiliated Hospital of Henan University of Science and Technology, Anyang, Henan, 455001, China; Department of Thoracic Surgery, Anyang Tumor Hospital, Anyang, Henan, 455001, China.
⁸ Department of Medical Biochemistry and Molecular Biology, School of Medicine, Jinan University, Guangzhou, 510632, China.
⁹ College of Clinical Medicine, The First Affiliated Hospital of Henan University of Science and Technology, Henan Key Laboratory of Cancer Epigenetics, Luoyang, 471003, China. Electronic address: gsg112258@163.com.
¹⁰ Department of Emergency Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹¹ 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. Electronic address: haolabcancercenter@163.com.

PMID: 33388371
DOI: 10.1016/j.canlet.2020.10.052

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_aschiRNA) 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_aschiRNA level in ESCC tissues was associated with tumor progression and patients' outcome. In vitro and in vivo studies demonstrated that A-P_aschiRNA aggravated ESCC metastasis and enhanced stemness through modulating OCT4. Mechanistic studies demonstrated that ERK5-mediated non-canonical PAF1 activity was required for A-P_aschiRNA-induced cancer malignancy. The study defined an undocumented function of chimeric RNAs in aggravating cancer stemness and metastasis.

Keywords: Chimeric RNA; Esophageal squamous cell carcinoma; Metastasis; Stemness.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Disease Progression
Esophageal Neoplasms / genetics*
Esophageal Neoplasms / metabolism
Esophageal Neoplasms / pathology
Esophageal Squamous Cell Carcinoma / genetics*
Esophageal Squamous Cell Carcinoma / metabolism
Esophageal Squamous Cell Carcinoma / pathology
Female
Glycoproteins / genetics*
Humans
Lymphatic Metastasis
Male
Middle Aged
Mitogen-Activated Protein Kinase 7 / genetics
Mitogen-Activated Protein Kinase 7 / metabolism
Neoplasm Metastasis
Neoplastic Stem Cells / pathology
Nerve Tissue Proteins / genetics*
Pregnancy-Associated Plasma Protein-A / genetics*
RNA / genetics
RNA, Messenger / genetics*
Transcription Factors / genetics
Transcription Factors / metabolism

Substances

ASTN2 protein, human
Glycoproteins
Nerve Tissue Proteins
PAF1 protein, human
PAPPAS gene product, human
RNA, Messenger
Transcription Factors
RNA
MAPK7 protein, human
Mitogen-Activated Protein Kinase 7
Pregnancy-Associated Plasma Protein-A
PAPPA protein, human