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miR-28-5p-CAMTA2 轴通过 Wnt/β-catenin 信号通路调节结肠癌的进展。

The miR-28-5p-CAMTA2 axis regulates colon cancer progression via Wnt/β-catenin signaling.

机构信息

Department of General Surgery, Dalian Municipal Central Hospital, Dalian, China.

出版信息

J Cell Biochem. 2021 Sep;122(9):945-957. doi: 10.1002/jcb.29536. Epub 2019 Nov 10.

Abstract

Colon cancer is the third most commonly diagnosed cancer with high morbidity and mortality. Calmodulin-binding transcription activator 2 (CAMTA2) belongs to the calmodulin-binding transcription activator protein family. The functional role of CAMTA2 in colon cancer development remains unclear. Our research found out that CAMTA2 was high-level expressed in colon cancer, and the upregulated CAMTA2 expression was markedly correlated with poor survival. Functional experiments showed that knockdown of CAMTA2 repressed colon cancer cell proliferation/migration in vitro and attenuated proliferation in vivo. In additional, CAMTA2 expression was controlled by miR-28-5p via posttranscriptional regulation and miR-28-5p expression was reversely correlated with CAMTA2 expression in colon cancer. Moreover, enforced miR-28-5p expression downregulated the expression of CAMTA2 significantly and the restoration of CAMTA2 expression abolished the inhibitory effect of miR-28-5p on colon cancer cell proliferation and metastasis. Mechanistically, overexpression of miR-28-5p suppressed Wnt/β-catenin signaling and the inhibitory could be partly abolished by overexpression of CAMTA2. In summary, our findings reveal that miR-28-5p/CAMTA2 axis plays a critical role in human colon cancer, which might be a promising diagnosis and therapeutic target for colon cancer treatment.

摘要

结肠癌是发病率和死亡率都很高的第三大常见癌症。钙调蛋白结合转录激活因子 2(CAMTA2)属于钙调蛋白结合转录激活蛋白家族。CAMTA2 在结肠癌发展中的功能作用尚不清楚。我们的研究发现,CAMTA2 在结肠癌中呈高水平表达,上调的 CAMTA2 表达与不良预后显著相关。功能实验表明,CAMTA2 敲低抑制了体外结肠癌细胞的增殖/迁移,并减弱了体内的增殖。此外,CAMTA2 的表达受 miR-28-5p 通过转录后调控控制,miR-28-5p 的表达与结肠癌中 CAMTA2 的表达呈负相关。此外,强制表达 miR-28-5p 可显著下调 CAMTA2 的表达,而恢复 CAMTA2 的表达可消除 miR-28-5p 对结肠癌细胞增殖和转移的抑制作用。在机制上,miR-28-5p 的过表达抑制了 Wnt/β-catenin 信号通路,而 CAMTA2 的过表达可部分消除这种抑制作用。总之,我们的研究结果表明,miR-28-5p/CAMTA2 轴在人结肠癌中起着关键作用,可能是结肠癌治疗有前途的诊断和治疗靶点。

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