Long non-coding RNA MCF2L-AS1 promotes the aggressiveness of colorectal cancer by sponging miR-874-3p and thereby up-regulating CCNE1.

BACKGROUND

Long non-coding 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. The present study aimed to explore the clinical significance and the biological effects of lncRNA MCF2L antisense RNA 1 (MCF2L-AS1) in CRC.

METHODS

Reverse transcriptase-polymerase chain reaction was performed to determine the expression of MCF2L-AS1 in CRC. The clinical significance of MCF2L-AS1 in CRC patients was analyzed statistically. 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-pulldown assays were performed to predict for potential microRNAs 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 the 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 also 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.