Long noncoding RNA MCF2L-AS1 promotes the aggressiveness of colorectal cancer by sponging miR-874-3p and thereby upregulating CCNE1

Colorectal Cancer
10/10/2020

J Gene Med. 2020 Oct 10:e3285. doi: 10.1002/jgm.3285. Online ahead of print.

ABSTRACT

BACKGROUND: Long noncoding RNAs (lncRNAs) have drawn growing attention because of the role which they play in various diseases, including colorectal cancer (CRC). However, the potential functions of lncRNA MCF2L antisense RNA 1 (MCF2L-AS1) in tumors remained largely unclear. In this study, we aimed to explore the clinical significance and the biological effects of lncRNA MCF2L antisense RNA 1(MCF2L-AS1) in CRC.

METHODS: RT-PCR was performed to determine the expression of MCF2L-AS1 in CRC. The clinical significance of MCF2L-AS1 in CRC patients was statistically analyzed. In vitro experiments were performed to determine the effects of MCF2L-AS1 on the cellular progression of CRC cells. Bioinformatic assays, luciferase reporter assays and RNA-pull down assays were performed to predict for potential miRNAs that can interact with MCF2L-AS1 and mRNAs that can interact with miR-874-3p.

RESULTS: We identified a novel CRC-related lncRNA, MCF2L-AS1 which is distinctly highly expressed in CRC. Its diagnostic value for CRC patients was also demonstrated. Clinical assays revealed that high MCF2L-AS1 expression is associated with advanced stages, positive metastasis and poor prognosis of CRC patients. Multivariate assays confirmed that MCF2L-AS1 expression is an independent poor prognostic factor for both 5-year overall survival and 5-year disease-free survival of CRC patients. Functionally, we confirmed that knockdown of MCF2L-AS1 distinctly suppresses the proliferation, migration and invasion of CRC cells, and promotes apoptosis. Mechanistic investigation showed that MCF2L-AS1 functions as an endogenous sponge for miR-874-3p to increase the expression of CCNE1.

CONCLUSIONS: Our findings identified a novel CRC-related lncRNA, MCF2L-AS1 which may be used as a potential diagnostic and prognostic biomarker for CRC patients. In addition, the newly identified MCF2L-AS1/miR-874-3p/CCNE1 axis can modulate the initiation and progression of CRC.