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RNA结合蛋白CUGBP1通过调节表皮生长因子受体(ErbB)信号通路介导结直肠癌肝转移。

RNA binding protein CUGBP1 mediates the liver metastasis of colorectal cancer by regulating the ErbB signal pathway.

作者信息

Qi Zhi-Peng, Chen Zhang-Han, He Dong-Li, Cai Shi-Lun, Li Bing, Sun Di, Lv Zhen-Tao, Xu En-Pan, Shi Qiang, Zhong Yun-Shi, Xu Jian-Min

机构信息

Endoscopy Center, Zhongshan Hospital of Fudan University, Shanghai, China.

Endoscopy Research Institute of Fudan University, Shanghai, China.

出版信息

Transl Cancer Res. 2021 Jul;10(7):3373-3388. doi: 10.21037/tcr-21-311.

Abstract

BACKGROUND

The CUGBP1 (CELF1) is differentially expressed in liver metastasis and no liver metastasis colorectal cancers (CRC) tissues and the function of CUGBP1 in CRC is still unclear.

METHODS

Five cases of colorectal adenocarcinoma and 6 cases of liver metastatic CRC lesions were collected and subjected to cDNA microarray and bioinformatical analyses. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to confirm the result. Cell function assays were used to study the function of CUGBP1, and the western blot was used to discover the change of the downstream molecules.

RESULTS

CUGBP1 was significantly elevated in liver metastatic CRC lesions. Besides, the CUGBP1 can promote proliferation, colony formation, invasion, metastasis abilities as well as increase the apoptosis rates of CRC cells. ERBB2 was positively related to the CUGBP1. Western blot results found that silence of CUGBP1 decreased the protein level of p-AKT and p-ERK without influence the expression level of total protein of AKT and ERK.

CONCLUSIONS

CUGBP1 can promote liver metastasis of CRC by promoting the phosphorylation of AKT and ERK through the ErbB signaling pathway. CUGBP1 is a potential biomarker for early detection of CRC and maybe a novel therapeutic target of CRC treatment, especially in liver metastasis.

摘要

背景

CUGBP1(CELF1)在有肝转移和无肝转移的结直肠癌(CRC)组织中表达存在差异,其在CRC中的功能仍不清楚。

方法

收集5例结直肠腺癌和6例肝转移CRC病变组织,进行cDNA微阵列和生物信息学分析。采用定量逆转录-聚合酶链反应(qRT-PCR)验证结果。通过细胞功能实验研究CUGBP1的功能,并用蛋白质印迹法检测下游分子的变化。

结果

CUGBP1在肝转移CRC病变中显著升高。此外,CUGBP1可促进CRC细胞的增殖、集落形成、侵袭和转移能力,并增加其凋亡率。ERBB2与CUGBP1呈正相关。蛋白质印迹结果显示,沉默CUGBP1可降低p-AKT和p-ERK的蛋白水平,而不影响AKT和ERK总蛋白的表达水平。

结论

CUGBP1可通过ErbB信号通路促进AKT和ERK磷酸化,从而促进CRC肝转移。CUGBP1是CRC早期检测的潜在生物标志物,可能是CRC治疗尤其是肝转移治疗的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/327b/8798417/67b61fa8241e/tcr-10-07-3373-f1.jpg

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