Super-enhancer-associated long noncoding RNA AC005592.2 promotes tumor progression by regulating OLFM4 in colorectal cancer

Linping Yan,Li Tang,Huanhuan Chen,Feng Yan,Pan Jiang

doi:10.1186/s12885-021-07900-x

Linping Yan, Li Tang + Show 3 more

Open Access

https://doi.org/10.1186/s12885-021-07900-x

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Journal: BMC Cancer	Publication Date: Feb 23, 2021
Citations: 11	License type: open-access

Affiliation: Jiangsu Cancer Hospital, Nanjing Medical University

Abstract

BackgroundSuper-enhancer-associated long noncoding RNAs (SE-lncRNAs) have been reported to play essential roles in tumorigenesis, but the fundamental mechanism of SE-lncRNAs in colorectal cancer (CRC) remains largely unknown.MethodsA microarray was performed to identify the differentially expressed SE-lncRNAs between CRC tissues and peritumoral tissues. A novel SE-lncRNA, AC005592.2, was selected from these differentially expressed SE-lncRNAs to explore its effects on CRC development. Fluorescence quantitative real-time PCR (qRT-PCR) was used to assay the expression of AC005592.2 in CRC tissues and cell lines. Functional assays were applied to identify the biological effects of AC005592.2 in CRC cells. Furthermore, RNA-seq was employed to predict potential targets of AC005592.2.ResultsAC005592.2 was significantly increased in CRC tissues and cells. High expression of AC005592.2 was significantly associated with TNM stage and tumor differentiation in CRC patients. Knockdown of AC005592.2 suppressed CRC cell proliferation, invasion and migration but promoted apoptosis, while AC005592.2 overexpression exerted the opposite effects on CRC cells. In addition, AC005592.2 positively regulated the expression of olfactomedin 4 (OLFM4), which was also upregulated in CRC tissues.ConclusionThe findings suggested that AC005592.2 is a crucial promoter of CRC progression and may serve as an attractive therapeutic target for CRC.

Highlights

Super-enhancer-associated long noncoding RNAs (SE-lncRNAs) have been reported to play essential roles in tumorigenesis, but the fundamental mechanism of SE-lncRNAs in colorectal cancer (CRC) remains largely unknown
As shown in boxplot line diagrams of SE-lncRNAs and mRNAs (Fig. 1a, b), the distribution of SE-lncRNA and mRNA signal values were properly symmetrical, and SE-lncRNAs were at lower levels than mRNAs in CRC, which is consistent with previous reports in other tissues [16]
These data confirmed that the expression of SElncRNAs undergoes a change that cannot be ignored during CRC tumorigenesis

Summary

Introduction

Super-enhancer-associated long noncoding RNAs (SE-lncRNAs) have been reported to play essential roles in tumorigenesis, but the fundamental mechanism of SE-lncRNAs in colorectal cancer (CRC) remains largely unknown. In. Yan et al BMC Cancer (2021) 21:187 multiple types of mammalian cells, SEs are closely related to essential lineage-specific genes that can be used to regulate gene expression and confirm cell-type specificity by increasing gene transcription over vast genomic distances [2, 4]. SEs can regulate the expression of oncogenes and other transcripts important for tumor pathogenesis [5, 6]. Super-enhancer-associated lncRNAs long noncoding RNAs (SE-lncRNAs) are a specific set of lncRNAs transcribed from SE genomic regions. CCAT1-L positively regulates MYC expression by mediating chromatin looping between the MYC promoter and its enhancers to promote CRC progression [11]

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Conclusion