Overexpression of MLF1IP promotes colorectal cancer cell proliferation through BRCA1/AKT/p27 signaling pathway

Background and objective: MLF1IP has been correlated with the progression and prognosis of a few tumors. However, the role of MLF1IP in colorectal cancer remains unclear. Here, we examined the expression and function of MLF1IP in colorectal cancer and investigated possible molecular mechanisms.

Methods: MLF1IP expressions in colorectal cancer tissues and cell lines were detected by quantitative real-time PCR, western blotting, and immunohistochemistry. In vitro and in vivo assays were performed to explore the function and underlying molecular mechanisms of MLF1IP in colorectal cancer.

Results: The expression levels of MLF1IP were significantly up-regulated in colorectal cancer tissues and CRC cell lines (P < 0.05). High expression of MLF1IP was significantly associated with TNM stage, T classification, lymph node involvement, distant metastasis, and poor patient survival (all P < 0.05). Overexpressing MLF1IP promoted while silencing MLF1IP inhibited, the proliferation and clonogenicity of colorectal cancer cells and tumorigenicity in NOD/SCID mice (P < 0.05). In addition, we demonstrated that the pro-proliferative effect of MLF1IP on colorectal cancer cells was associated with mediating the G1-to-S phase transition. MLF1IP knockdown enhanced BRCA1 activity concomitantly with p-AKT downregulation and p27 upregulation, while overexpression of MLF1IP has the opposite effect. Moreover, upregulation of BRCA1 can partially abolish the proliferative activity of MLF1IP.

Conclusions: These findings suggest that MLF1IP may promote proliferation and tumorigenicity of colorectal cancer cells via BRCA1/AKT/p27 signaling axis, and thereby provides potential targets for colorectal cancer therapy.