Home Neoplasma 2023 Neoplasma Vol.70, No.5, p. 597–609, 2023

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ISSN 0028-2685
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Neoplasma Vol.70, No.5, p. 597–609, 2023

Title: RNASEH1-AS1 induced by H3K27ac stabilizes ANXA2 mRNA to promote the progression of colorectal cancer through recruiting BUD13
Author: Shengwei Zhuang, Weihong Lu, Lianjun Shen, Zhekun Huang, Xiuping Zhang, Yong Zhang

Abstract: Colorectal cancer (CRC) is a malignant tumor with high morbidity and mortality. It is well-accepted that dysregulated lncRNAs are closely related to the development of CRC. In this study, the function and mechanism of RNASEH1-AS1 in CRC were investigated. RT-qPCR and western blot detected the expression of targeted genes in tissues and cells. CCK-8, clone formation, wound healing assay, and Transwell were applied to evaluate CRC cell malignant behaviors. ChIP, RIP, and RNA pull-down validated interactions among RNASEH1-AS1, H3K27ac, CBP, BUD13, and ANXA2. Nucleoplasmic separation and FISH assay determined the location of RNASEH1-AS1 in CRC cells. IHC assay was used to detect Ki-67 expression in tumor tissues from mice. RNASEH1-AS1 was highly expressed in CRC tumor tissues and cells. RNASEH1-AS1 silencing effectively suppressed the viability, proliferation, migration, and invasion of CRC cells. In addition, CBP-mediated H3K27ac increased RNASEH1-AS1 expression in CRC cells and RNASEH1-AS1 could elevate ANXA2 expression through recruiting BUD13. Furthermore, RNASEH1-AS1 silencing inhibited malignant phenotypes of CRC cells and tumor growth in mice through decreasing ANXA2 expression and inactivating the Wnt/β-catenin pathway. Our results revealed that RNASEH1-AS1 induced by CBP-mediated H3K27ac activated Wnt/β-catenin pathway to promote CRC progression through recruiting BUD13 to stabilize ANXA2 mRNA, which provides substantial evidence of RNASEH1-AS1 in CRC. Targeting RNASEH1-AS1 might alleviate CRC progression.

Keywords: colorectal cancer; H3K27ac; RNASEH1-AS1; BUD13; ANXA2
Published online: 06-Dec-2023
Year: 2023, Volume: 70, Issue: 5 Page From: 597, Page To: 609

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