Department of Pathology, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
Department of Pathology, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
Cell Signal. 2022 Apr;92:110273. doi: 10.1016/j.cellsig.2022.110273. Epub 2022 Feb 2.
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.
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.
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.
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.
MLF1IP 与几种肿瘤的进展和预后相关。然而，MLF1IP 在结直肠癌中的作用尚不清楚。在这里，我们研究了 MLF1IP 在结直肠癌中的表达和功能，并探讨了可能的分子机制。
通过实时定量 PCR、western blot 和免疫组织化学检测结直肠癌组织和细胞系中 MLF1IP 的表达。进行体外和体内实验以研究 MLF1IP 在结直肠癌中的功能及其潜在的分子机制。
MLF1IP 的表达水平在结直肠癌组织和 CRC 细胞系中明显上调（P<0.05）。高表达 MLF1IP 与 TNM 分期、T 分类、淋巴结受累、远处转移和患者生存不良显著相关（均 P<0.05）。过表达 MLF1IP 促进而沉默 MLF1IP 抑制结直肠癌细胞的增殖和集落形成能力以及 NOD/SCID 小鼠的肿瘤生成能力（P<0.05）。此外，我们证明 MLF1IP 对结直肠癌细胞的促增殖作用与介导 G1 至 S 期转变有关。MLF1IP 敲低同时增强 BRCA1 活性，下调 p-AKT 和上调 p27，而过表达 MLF1IP 则具有相反的效果。此外，BRCA1 的上调可部分消除 MLF1IP 的增殖活性。
这些发现表明，MLF1IP 可能通过 BRCA1/AKT/p27 信号通路促进结直肠癌细胞的增殖和致瘤性，从而为结直肠癌治疗提供了潜在的靶点。
