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

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

doi:10.21037/tcr-21-311

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

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

Authors

Zhi-Peng Qi^#^{1

2}, Zhang-Han Chen^#^{1

2}, Dong-Li He^#³, Shi-Lun Cai^{1

2}, Bing Li^{1

2}, Di Sun^{1

2}, Zhen-Tao Lv^{1

2}, En-Pan Xu^{1

2}, Qiang Shi^{1

2

4}, Yun-Shi Zhong^{1

2

4}, Jian-Min Xu⁵

Affiliations

¹ Endoscopy Center, Zhongshan Hospital of Fudan University, Shanghai, China.
² Endoscopy Research Institute of Fudan University, Shanghai, China.
³ Department of Internal Medicine of Xuhui Hospital, Affiliated Zhongshan Hospital, Fudan University, Shanghai, China.
⁴ Endoscopy Center of Xuhui Hospital, Affiliated Zhongshan Hospital, Fudan University, Shanghai, China.
⁵ General Surgery Department, Zhongshan Hospital, Fudan University, Shanghai, China.

^# Contributed equally.

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.

Keywords: Colorectal cancer (CRC); ErbB signaling pathway; Human CUG-binding protein; cDNA microarray; liver metastasis.