Abstract
BackgroundEmerging studies suggest that long non-coding RNAs (lncRNAs) play crucial roles in colorectal cancer (CRC). Here, we report a lncRNA, SATB2-AS1, which is specifically expressed in colorectal tissue and is significantly reduced in CRC. We systematically elucidated its functions and possible molecular mechanisms in CRC.MethodsLncRNA expression in CRC was analyzed by RNA-sequencing and RNA microarrays. The expression level of SATB2-AS1 in tissues was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH). The functional role of SATB2-AS1 in CRC was investigated by a series of in vivo and in vitro assays. RNA pull-down, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), chromatin isolation by RNA purification (ChIRP), Bisulfite Sequencing PCR (BSP) and bioinformatics analysis were utilized to explore the potential mechanisms of SATB2-AS1.ResultsSATB2-AS1 is specifically expressed in colorectal tissues and downregulated in CRC. Survival analysis indicates that decreased SATB2-AS1 expression is associated with poor survival. Functional experiments and bioinformatics analysis revealed that SATB2-AS1 inhibits CRC cell metastasis and regulates TH1-type chemokines expression and immune cell density in CRC. Mechanistically, SATB2-AS1 directly binds to WDR5 and GADD45A, cis-activating SATB2 (Special AT-rich binding protein 2) transcription via mediating histone H3 lysine 4 tri-methylation (H3K4me3) deposition and DNA demethylation of the promoter region of SATB2.ConclusionsThis study reveals the functions of SATB2-AS1 in CRC tumorigenesis and progression, suggesting new biomarkers and therapeutic targets in CRC.
Highlights
Emerging studies suggest that long non-coding RNAs play crucial roles in colorectal cancer (CRC)
Colorectal tissue-specific long non-coding RNAs (lncRNAs) Special AT-rich binding protein 2 (SATB2)-AS1 is downregulated in CRC tissues and predicts a good prognosis To discover the lncRNAs that was involved in CRC, we first analyzed the lncRNA expression profiles of CRC in two independent cohorts
We identified a series of abnormally expressed lncRNAs in CRC and found that SATB2-AS1 was significantly decreased in both cohorts (Fig. 1a, Additional file 3: Figure S1a)
Summary
Emerging studies suggest that long non-coding RNAs (lncRNAs) play crucial roles in colorectal cancer (CRC). We report a lncRNA, SATB2-AS1, which is expressed in colorectal tissue and is significantly reduced in CRC. We systematically elucidated its functions and possible molecular mechanisms in CRC. CRC is the third most common cancer by incidence and the fourth leading cause of cancer death worldwide [1]. Some advances have been made in its diagnosis and treatment, patients with advanced CRC have a poor prognosis. Recurrence, metastasis and drug resistance are common causes of poor prognosis in patients with CRC [2]. Accumulating evidence reveals that lncRNAs are important regulators of gene expression and are involved in various physiological and pathological processes, including the occurrence and development of tumors [5]. Xu et al Molecular Cancer (2019) 18:135
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