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Background

SLCO4A1-AS1 was found to be upregulated in several cancer types, including colorectal cancer (CRC). However, the detailed roles of SLCO4A1-AS1 in CRC remain to be elucidated. Therefore, we investigated the functions, mechanism, and clinical significance of SLCO4A1-AS1 in colorectal tumourigenesis.

Methods

We measured the expression of SLCO4A1-AS1 in CRC tissues using qRT-PCR and determined its correlation with patient prognosis. Promoter methylation analyses were used to assess the methylation status of SLCO4A1-AS1. Gain- and loss-of-function assays were used to evaluate the effects of SLCO4A1-AS1 on CRC growth in vitro and in vivo. RNA pull-down, RNA immunoprecipitation, RNA-seq, luciferase reporter and immunohistochemistry assays were performed to identify the molecular mechanism of SLCO4A1-AS1 in CRC.

Results

SLCO4A1-AS1 was frequently upregulated in CRC tissues based on multiple CRC cohorts and was associated with poor prognoses. Aberrant overexpression of SLCO4A1-AS1 in CRC is partly attributed to the DNA hypomethylation of its promoter. Ectopic SLCO4A1-AS1 expression promoted CRC cell growth, whereas SLCO4A1-AS1 knockdown repressed CRC proliferation both in vitro and in vivo. Mechanistic investigations revealed that SLCO4A1-AS1 functions as a molecular scaffold to strengthen the interaction between Hsp90 and Cdk2, promoting the protein stability of Cdk2. The SLCO4A1-AS1-induced increase in Cdk2 levels activates the c-Myc signalling pathway by promoting the phosphorylation of c-Myc at Ser62, resulting in increased tumour growth.

Conclusions

Our data demonstrate that SLCO4A1-AS1 acts as an oncogene in CRC by regulating the Hsp90/Cdk2/c-Myc axis, supporting SLCO4A1-AS1 as a potential therapeutic target and prognostic factor for CRC."xsd:string
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http://purl.uniprot.org/citations/35039060http://purl.uniprot.org/core/author"Huang L."xsd:string
http://purl.uniprot.org/citations/35039060http://purl.uniprot.org/core/author"Huang S."xsd:string
http://purl.uniprot.org/citations/35039060http://purl.uniprot.org/core/author"Li C."xsd:string
http://purl.uniprot.org/citations/35039060http://purl.uniprot.org/core/author"Huang Z."xsd:string
http://purl.uniprot.org/citations/35039060http://purl.uniprot.org/core/author"Zhou L."xsd:string
http://purl.uniprot.org/citations/35039060http://purl.uniprot.org/core/author"Zhang J."xsd:string
http://purl.uniprot.org/citations/35039060http://purl.uniprot.org/core/author"Wang X."xsd:string
http://purl.uniprot.org/citations/35039060http://purl.uniprot.org/core/author"Yang F."xsd:string
http://purl.uniprot.org/citations/35039060http://purl.uniprot.org/core/author"Yin Y."xsd:string
http://purl.uniprot.org/citations/35039060http://purl.uniprot.org/core/author"Sun S."xsd:string
http://purl.uniprot.org/citations/35039060http://purl.uniprot.org/core/author"Bian Z."xsd:string
http://purl.uniprot.org/citations/35039060http://purl.uniprot.org/core/author"Cui K."xsd:string
http://purl.uniprot.org/citations/35039060http://purl.uniprot.org/core/author"Fei B."xsd:string
http://purl.uniprot.org/citations/35039060http://purl.uniprot.org/core/date"2022"xsd:gYear
http://purl.uniprot.org/citations/35039060http://purl.uniprot.org/core/name"J Biomed Sci"xsd:string
http://purl.uniprot.org/citations/35039060http://purl.uniprot.org/core/pages"4"xsd:string
http://purl.uniprot.org/citations/35039060http://purl.uniprot.org/core/title"SLCO4A1-AS1 promotes colorectal tumourigenesis by regulating Cdk2/c-Myc signalling."xsd:string
http://purl.uniprot.org/citations/35039060http://purl.uniprot.org/core/volume"29"xsd:string
http://purl.uniprot.org/citations/35039060http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/35039060
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