A novel lncRNA LOC101928222 promotes colorectal cancer angiogenesis by stabilizing HMGCS2 mRNA and increasing cholesterol synthesis.
J Exp Clin Cancer Res
; 43(1): 185, 2024 Jul 04.
Article
em En
| MEDLINE
| ID: mdl-38965575
ABSTRACT
BACKGROUND:
Metastasis is the leading cause of mortality in patients with colorectal cancer (CRC) and angiogenesis is a crucial factor in tumor invasion and metastasis. Long noncoding RNAs (lncRNAs) play regulatory functions in various biological processes in tumor cells, however, the roles of lncRNAs in CRC-associated angiogenesis remain to be elucidated in CRC, as do the underlying mechanisms.METHODS:
We used bioinformatics to screen differentially expressed lncRNAs from TCGA database. LOC101928222 expression was assessed by qRT-PCR. The impact of LOC101928222 in CRC tumor development was assessed both in vitro and in vivo. The regulatory mechanisms of LOC101928222 in CRC were investigated by cellular fractionation, RNA-sequencing, mass spectrometric, RNA pull-down, RNA immunoprecipitation, RNA stability, and gene-specific m6A assays.RESULTS:
LOC101928222 expression was upregulated in CRC and was correlated with a worse outcome. Moreover, LOC101928222 was shown to promote migration, invasion, and angiogenesis in CRC. Mechanistically, LOC101928222 synergized with IGF2BP1 to stabilize HMGCS2 mRNA through an m6A-dependent pathway, leading to increased cholesterol synthesis and, ultimately, the promotion of CRC development.CONCLUSIONS:
In summary, these findings demonstrate a novel, LOC101928222-based mechanism involved in the regulation of cholesterol synthesis and the metastatic potential of CRC. The LOC101928222-HMGCS2-cholesterol synthesis pathway may be an effective target for diagnosing and managing CRC metastasis.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
RNA Mensageiro
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Neoplasias Colorretais
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Colesterol
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RNA Longo não Codificante
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Neovascularização Patológica
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article