Long noncoding RNA LINC01594 inhibits the CELF6-mediated splicing of oncogenic CD44 variants to promote colorectal cancer metastasis.-Reference-Cited by-同舟云学术

Long noncoding RNA LINC01594 inhibits the CELF6-mediated splicing of oncogenic CD44 variants to promote colorectal cancer metastasis.

Published:2023-01-25 Issue: Volume: Page:
ISSN:
Container-title:
language:
Short-container-title:

Author:

Liu Bo-Wen¹,Song Angxi¹,Gui Pengkun¹,Wang Jin¹,Pan Yao-Jie¹^ORCID,Li Chao¹,Li Shuai¹,Zhang Yi²,Jiang Tao³,Xu Yi-Xin²,Huo Fu-Chun,Pei Dong-Sheng¹^ORCID,Song Jun³

Affiliation:

1. Xuzhou Medical University

2. Affiliated Hospital of Xuzhou Medical University

3. The Affiliated Hospital of Xuzhou Medical University

Abstract

Abstract Long noncoding RNAs (lncRNAs) play critical roles in tumorigenesis and tumor metastasis. However, the underlying mechanisms of lncRNAs in colorectal cancer (CRC) need further exploration. By using data from The Cancer Genome Atlas (TCGA) and GEO databases, we identified a novel CRC-related lncRNA, LINC01594, that is significantly upregulated in CRC and associated with poor prognosis. In vitro and in vivo, gain- and loss-of-function experiments demonstrated that LINC01594 promotes metastasis in CRC. LINC01594 functions as a DNMT1 scaffold, increasing the level of CELF6 promoter methylation. LINC01594 also competitively binds the transcription factor p53, decreasing CELF6 expression. This inhibited the exon skipping of CD44 V4-V7 induced by CELF6. In summary, this study highlights a novel CRC biomarker and therapeutic target, LINC01594, and the findings suggest that the LINC01594-CELF6-CD44 axis might serve as a biomarker and therapeutic target in CRC.

Publisher

Research Square Platform LLC

Reference58 articles.

1. 1. Bray, F. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68: 394–424, doi:10.3322/caac.21492.

2. 2. Dekker, E., Tanis, P. J., Vleugels, J. L. A., Kasi, P. M. & Wallace, M. B. Colorectal cancer. Lancet. 2019; 394: 1467–1480, doi:10.1016/S0140-6736(19)32319-0.

3. 3. Ganesh, K. et al. Immunotherapy in colorectal cancer: rationale, challenges and potential. Nat Rev Gastroenterol Hepatol. 2019; 16: 361–375, doi:10.1038/s41575-019-0126-x.

4. 4. Kazemzadeh, M., Safaralizadeh, R. & Orang, A. V. LncRNAs: emerging players in gene regulation and disease pathogenesis. J Genet. 2015; 94: 771–784, doi:10.1007/s12041-015-0561-6.

5. 5. Fatica, A. & Bozzoni, I. Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet. 2014; 15: 7–21, doi:10.1038/nrg3606.