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M6A-modified lncRNA FAM83H-AS1 promotes colorectal cancer progression through PTBP1.
- Source :
-
Cancer letters [Cancer Lett] 2024 Aug 28; Vol. 598, pp. 217085. Date of Electronic Publication: 2024 Jul 02. - Publication Year :
- 2024
-
Abstract
- LncRNA plays a crucial role in cancer progression and targeting, but it has been difficult to identify the critical lncRNAs involved in colorectal cancer (CRC) progression. We identified FAM83H-AS1 as a tumor-promoting associated lncRNA using 21 pairs of stage IV CRC tissues and adjacent normal tissues. In vitro and in vivo experiments revealed that knockdown of FAM83H-AS1 in CRC cells inhibited tumor proliferation and metastasis, and vice versa. M6A modification is critical for FAM83H-AS1 RNA stability through the writer METTL3 and the readers IGF2BP2/IGFBP3. PTBP1-an RNA binding protein-is responsible for the FAM83H-AS1 function in CRC. T4 (1770-2440 nt) and T5 (2440-2743 nt) on exon 4 of FAM83H-AS1 provide a platform for PTBP1 RRM2 interactions. Our results demonstrated that m6A modification dysregulated the FAM83H-AS1 oncogenic role by phosphorylated PTBP1 on its RNA splicing effect. In patient-derived xenograft models, ASO-FAM83H-AS1 significantly suppressed the growth of gastrointestinal (GI) tumors, not only CRC but also GC and ESCC. The combination of ASO-FAM83H-AS1 and oxaliplatin/cisplatin significantly suppressed tumor growth compared with treatment with either agent alone. Notably, there was pathological complete response in all these three GI cancers. Our findings suggest that FAM83H-AS1 targeted therapy would benefit patients primarily receiving platinum-based therapy in GI cancers.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Humans
Animals
Mice
Cell Line, Tumor
Adenosine analogs & derivatives
Adenosine metabolism
Male
Female
Xenograft Model Antitumor Assays
Mice, Nude
RNA Stability
Cell Movement
Mice, Inbred BALB C
Ribonucleoside Diphosphate Reductase
RNA-Binding Proteins
Polypyrimidine Tract-Binding Protein genetics
Polypyrimidine Tract-Binding Protein metabolism
RNA, Long Noncoding genetics
Colorectal Neoplasms genetics
Colorectal Neoplasms pathology
Colorectal Neoplasms metabolism
Heterogeneous-Nuclear Ribonucleoproteins genetics
Heterogeneous-Nuclear Ribonucleoproteins metabolism
Cell Proliferation
Disease Progression
Methyltransferases genetics
Methyltransferases metabolism
Gene Expression Regulation, Neoplastic
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7980
- Volume :
- 598
- Database :
- MEDLINE
- Journal :
- Cancer letters
- Publication Type :
- Academic Journal
- Accession number :
- 38964733
- Full Text :
- https://doi.org/10.1016/j.canlet.2024.217085