Overexpression of MLF1IP promotes colorectal cancer cell proliferation through BRCA1/AKT/p27 signaling pathway.
Overexpression of MLF1IP promotes colorectal cancer cell proliferation through BRCA1/AKT/p27 signaling pathway.
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DOI：
10.1016/j.cellsig.2022.110273
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发表时间：
2022-02
影响因子：
4.8
通讯作者：
Yuting Xu;Lin Zhang;Qingling Wang;Maojin Zheng
中科院分区：
文献类型：
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作者：
Yuting Xu;Lin Zhang;Qingling Wang;Maojin Zheng
背景与目的MLF 1 IP与一些肿瘤的进展和预后有关。然而，MLF 1 IP在结直肠癌中的作用仍不清楚。本研究采用实时荧光定量PCR、Western blotting、RT-PCR和Western blot等方法检测大肠癌组织和细胞系中MLF 1 IP的表达，并探讨其在大肠癌中的作用机制。体外和体内实验研究了MLF 1 IP在结直肠癌中的作用及其分子机制。在大肠癌组织和大肠癌细胞系中表达上调（P< 0.05）。MLF 1 IP的高表达与乳腺癌的TNM分期、T分期、淋巴结转移、远处转移及生存率相关（均P <0.05）。过表达MLF 1 IP可促进NOD/SCID小鼠大肠癌细胞的增殖、克隆形成和致瘤性，而沉默MLF 1 IP则可抑制肿瘤细胞的增殖、克隆形成和致瘤性（P< 0.05）。此外，我们证明了MLF 1 IP对结直肠癌细胞的促增殖作用与介导G1至S期转变有关。MLF 1 IP敲低增强BRCA 1活性，同时伴有p-AKT下调和p27上调，而MLF 1 IP过表达具有相反的作用。结论MLF 1 IP可能通过BRCA 1/AKT/p27信号通路促进大肠癌细胞的增殖和致瘤性，为大肠癌的治疗提供了潜在的靶点。
Background and objectiveMLF1IP 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.MethodsMLF1IP expressions in colorectal cancer tissues and cell lines were detected by quantitative real-time PCR, western blotting, and immunohistochemistry.In vitroandin vivoassays were performed to explore the function and underlying molecular mechanisms of MLF1IP in colorectal cancer.ResultsThe 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 (allP<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.ConclusionsThese 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.