Transcription activation of SPINK4 by ELF-1 augments progression of colon cancer by regulating biological behaviors

Tissue Cell. 2023 Oct:84:102190. doi: 10.1016/j.tice.2023.102190. Epub 2023 Aug 2.

Abstract

Background: SPINK4 was highly expressed in colorectal cancer and resulted in worse prognosis of colorectal cancer patients. However, the expression and function of SPINK4 in colon cancer have not been revealed.

Methods: Analysis from GEPIA website showed the expression and function of SPINK4 in colon cancer samples. Colon cancer cell lines were applied to detect the biological function of SPINK4. Functionally, the transcriptional factor of SPINK4 has been predicted and verified. Finally, the associations between transcriptional factor and SPINK4 have been confirmed.

Results: SPINK4 expression was obviously increased in colon cancer samples. HCT-116 and DXH-1 cells in si-SPINK4-1 or si-SPINK4-2 group displayed an obvious reduction in its proliferation, cell cycle, invasion and migration compared to those in the si-control group. Moreover, transcriptional factor ELF-1 bound to the promoter of SPINK4 and affected its expression in colon cancer cells. High ELF-1 expression was presented in colon cancer samples and resulted in worse prognosis of colon cancer patients. Additionally, si-SPINK4 antagonized the function of ELF-1 overexpression in modulating colon cancer cell proliferation, cell cycle and mobility.

Conclusions: Our findings afforded a theoretical basis for further research on the treatment of colon cancer based on the control of ELF-1/SPINK4 expression.

Keywords: Cell cycle; Colon cancer; ELF-1; Proliferation; SPINK4.