SALL1 promotes proliferation and metastasis and activates phosphorylation of p65 and JUN in colorectal cancer cells

Jie Yuan; Guiying Li; Fei Zhong; Jiannan Liao; Zhiqiang Zeng; Shaoyong Ouyang; Hong Xie; Zhiliang Deng; Hongmei Tang; Xiaowei Ou

doi:10.1016/j.prp.2023.154827

SALL1 promotes proliferation and metastasis and activates phosphorylation of p65 and JUN in colorectal cancer cells

Pathol Res Pract. 2023 Oct:250:154827. doi: 10.1016/j.prp.2023.154827. Epub 2023 Sep 20.

Authors

Jie Yuan¹, Guiying Li², Fei Zhong³, Jiannan Liao², Zhiqiang Zeng⁴, Shaoyong Ouyang², Hong Xie², Zhiliang Deng², Hongmei Tang⁵, Xiaowei Ou⁶

Affiliations

¹ Department of General Surgery, Foshan Clinical Medical School, Guangzhou University of Chinese Medicine, Foshan 528000, China; Department of General Surgery, Foshan Fosun Chancheng Hospital, Foshan 528000, China. Electronic address: candlewjy@163.com.
² Department of General Surgery, Foshan Fosun Chancheng Hospital, Foshan 528000, China.
³ Department of General Surgery, Foshan Clinical Medical School, Guangzhou University of Chinese Medicine, Foshan 528000, China.
⁴ Department of General Surgery, Foshan Clinical Medical School, Guangzhou University of Chinese Medicine, Foshan 528000, China; Department of General Surgery, Foshan Fosun Chancheng Hospital, Foshan 528000, China.
⁵ Pharmaceutical Department, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510504, China.
⁶ Department of General Surgery, Foshan Fosun Chancheng Hospital, Foshan 528000, China. Electronic address: ouxiaowei@fsccyy.com.

PMID: 37741137
DOI: 10.1016/j.prp.2023.154827

Abstract

Background: Colorectal cancer (CRC) is one of the most usual malignant tumors, and its incidence continues to rise. Our purpose was to explore the function and potential regulatory mechanisms of SALL1, a differentially methylated gene in CRC, in vivo and in vitro.

Methods: Firstly, methylation differential gene SALL1 in CRC was screened and validated. SALL1 overexpression plasmids or SALL1 siRNAs were transfected in HT-29 and SW480 cells. Moreover, 10 μM T-5224 was added in SALL1-overexpressed CRC cells. CCK-8, flow cytometry and transwell assays were utilized to assess cell proliferation, cycle, migration, and invasion, respectively. Then CRC organoids were cultured. Next, HT-29 and SW480 cells transfected with SALL1 overexpression lentivirus were analyzed by transcriptome sequencing. Finally, in vivo tumorigenesis was used to analyze the effect of SALL1 overexpression on subcutaneous tumorigenesis in nude mice.

Results: The methylation level of CpG island in SALL1 promoter was increased in CRC tissues and could distinguish tumor tissues. Overexpression of SALL1 accelerated proliferation, migration and invasion of HT-29 and SW480 cells, and silencing of SALL1 attenuated proliferation, migration and invasion of HT-29 and SW480 cells. Through analysis and validation, we found that overexpression of SALL1 also could upregulate p-p65 and p-JUN expressions. Besides, c-Fos/activator protein (AP)- 1 inhibitor (T-5224) could reverse the induction of CRC progression by SALL1 overexpression. In vivo, we also proved that overexpression of SALL1 significantly increased tumor volume, tumor weight, and p-JUN expression.

Conclusions: SALL1 could promote the proliferation, migration, and invasion of CRC cells and activate phosphorylation of p65 and JUN.

Keywords: Colorectal cancer; Metastasis; Methylation; SALL1.