FOXCUT Promotes the Proliferation and Invasion by Activating FOXC1/PI3K/AKT Pathway in Colorectal Cancer

Colorectal cancer (CRC) is the third most commonly diagnosed world cancer. Long noncoding RNAs (lncRNAs) serve important regulatory roles in tumorigenesis. However, the contributions of lncRNAs to human CRC remain largely unknown.

FOXC1 and FOXCUT lncRNA expression levels were detected in a panel of paired specimens obtained from 48 patients' tissues and cell lines with CRC using RT-qPCR. RNA interference was used to investigate potential correlations between FOXC1 and FOXCUT expression in HT29. Cell proliferation was assessed by MTT assay and EdU incorporation assay. The migration and invasion of CRC cells were detected by transwell assay. Western blot was applied to assess the protein expression and PI3K/AKT signaling pathway.

In this study, a novel long noncoding RNA (FOXCUT) was frequently overexpressed in CRC tissues and cell lines. In addition, the expressions of FOXCUT and FOXC1 were positively correlated. When the expression of FOXCUT was downregulated by small interfering RNA (siRNA), the expression of FOXC1 was also decreased. Moreover, knockdown of FOXCUT significantly inhibited proliferation and invasion of CRC cell lines and resulted in downregulated expression of the matrix metalloproteinase 1 (MMP-1). Mechanistically, FOXCUT promotes the expression of FOXC1 to activate PI3K/AKT signaling pathway for its regulation of cell growth and proliferation.

In summary, our findings indicate that FOXCUT plays an important oncogenic role and may serve as a novel biomarker and therapeutic target in CRC progression.