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Research Paper|Volume 12, Issue 22|pp 22656—22687

Long non-coding RNA ZFAS1 promotes colorectal cancer tumorigenesis and development through DDX21-POLR1B regulatory axis

Xiufang Wang1,2, Zhikun Wu1,2, Wenyan Qin1,2, Tong Sun1,2, Senxu Lu1,2, Yalun Li3, Yuanhe Wang4, Xiaoyun Hu1,2, Dongping Xu1,2, Yutong Wu1,2, Qiuchen Chen1,2, Weifan Yao1,2, Mingyan Liu1,2, Minjie Wei1,2, Huizhe Wu1,2
  • 1Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang 110122, P. R. China
  • 2Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang 110122, P. R. China
  • 3Department of Anorectal Surgery, First Hospital of China Medical University, Shenyang 110001, P. R. China
  • 4Department of Medical Oncology, Cancer Hospital of China Medical University, Department of Medical Oncology, Liaoning Cancer Hospital and Institute, Shenyang 110042, P. R. China
Received: February 11, 2020Accepted: May 25, 2020Published: November 16, 2020
https://doi.org/10.18632/aging.103875

Copyright: © 2020 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Increasing evidence supports long non-coding RNA-ZFAS1 as master protein regulators involved in a variety of human cancers. However, the molecular mechanism is not fully understood in colorectal cancer (CRC) and remains to be elucidated. Here, we uncovered a previously unreported mechanism linking RNA helicase DDX21 regulated by lncRNA ZFAS1 in control of POLR1B expression in CRC initiation and progression. Specifically, ZFAS1 exerted its oncogenic functions and was significantly up-regulated accompanied by elevated DDX21, POLR1B expression in CRC cells and tissues, which further closely associated with poor clinical outcomes. Notably, ZFAS1 knockdown dramatically suppressed CRC cell proliferation, invasion, migration, and increased cell apoptosis, which were contrary to the effect caused by ZFAS1 up-regulation. We further revealed that the inhibitory effect caused by ZFAS1 knockdown could be reversed by DDX21 overexpression in vitro and in vivo. Mechanistically, our research found that ZFAS1 could directly recruit DDX21 protein by harboring the specific motif (AAGA or CAGA). Finally, POLR1B was identified as the downstream target of DDX21 regulated by ZFAS1, which was also up-regulated in CRC cells and tissues and closely related to poor prognosis. The unrecognized ZFAS1/DDX21/POLR1B signaling regulation axis may provide new biomarkers and targets for CRC treatment and prognostic evaluation.