Year-end Sale % OFF 
Abstract
BackgroundSLCO4A1-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.MethodsWe 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.ResultsSLCO4A1-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.ConclusionsOur 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.
Highlights
SLCO4A1-AS1 was found to be upregulated in several cancer types, including colorectal cancer (CRC)
We found that 14 candidate long noncoding RNAs (lncRNAs) were significantly increased in CRCs compared with paired noncancerous tissues (NCTs) (Additional file 3: Table S3)
SLCO4A1‐AS1 interacts with Hsp90 and Cdk2 in CRCTo further identify targets directly interacting with SLCO4A1-AS1, we firstly investigated the subcellular localization of SLCO4A1-AS1 using Quantitative RT-PCR (qRT-PCR) and Fluorescent in situ hybridization (FISH)
Summary
SLCO4A1-AS1 was found to be upregulated in several cancer types, including colorectal cancer (CRC). CRC exhibits abnormal expression patterns of lncRNAs, and some lncRNAs, including MEG3[6], SLCC1 [7], H19 [8], FEZF1-AS1 [9], UCA1 [10], and LINC00152 [11], have been reported to regulate colorectal tumourigenesis and progression by targeting tumour-related signalling pathways. We revealed that FEZF1-AS1 promote CRC growth and metastasis by regulating STAT3 signalling and glycolysis [9]. These data demonstrate the key roles of lncRNAs in the complicated pathogenesis of CRC
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
