LncRNA FLVCR1-AS1 functions as competing endogenous RNA (ceRNA) to sponge miR-381-3p and aggravate colorectal cancer via upregulation of Wnt signaling pathway

Abstract

Introduction Colorectal cancer (CRC) is the third most frequent cancer and the second deadliest cancer, worldwide. Long non-coding RNAs (lncRNAs) have been introduced as vital regulators of CRC. lncRNA feline leukemia virus subgroup C receptor 1 antisense RNA 1 (FLVCR1‑AS1) is suggested to play a significant role in the tumorigenesis of several cancers. Wnt signaling pathway is the most deregulated pathway in CRC. The present study aimed to investigate the underlying mechanism of function of FLVCR1-AS1 in CRC through FLVCR1-AS1/miR-381-3p/ CTNNB1, LRP6, FZD3 axis. Methods The expression level of FLVCR1-AS1 was compared between CRC tissues and adjacent normal tissues, and additionally between CRC cell lines. Knockdown of FLVCR1-AS1 was performed in HCT116 cells, afterwards, the effects of this knockdown on the expression levels of FLVCR1-AS1, miR-381-3p, and three genes was examined via Real time-PCR. The differences in proliferation were evaluated using MTT assay, and cell death was assessed by flow cytometry. Results The results confirmed that FLVCR1-AS1 was upregulated in CRC tissues compared to adjacent normal tissues. RT-qPCR validated that FLVCR1-AS1 has the most level of expression in HT29, HCT116, SW480, and Caco2; respectively. Knockdown of FLVCR1‑AS1 was significantly followed by attenuated viability of HCT116 cells; while resulted in enhanced apoptosis and necrosis. Conclusion These findings support the idea that FLVCR1-AS1 may act as an oncogene in CRC and targeting FLVCR1-AS1/miR-381-3p/ CTNNB1, LRP6, FZD3 axis may be introduced as a novel target for CRC therapy and diagnosis in the future.