ELF1's Role in Colorectal Cancer: Up-Regulating DCLK1 Expression to Propel Malignant Progression and Stemness Features.

Background: Exploring the pathological mechanism of colorectal cancer (CRC) onset and advancement is critical to clinical diagnosis and treatment. In this context, our study brings a novel perspective by investigating the role and regulatory mechanism of E74 Like ETS Transcription Factor 1 () in CRC, a topic that has not been extensively explored.

Methods: Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blotting (WB) assays were used to detect the expression of ELF1 in CRC cells. Sh-ELF1, ELF1 overexpresses lentivirus (Oe-ELF1), and Oe-Doublecortin Like Kinase 1 (DCLK1) were constructed and transfected into CRC cells. Transfection efficiency and the expression of stemness, as well as epithelial-mesenchymal transition (EMT)-related proteins were detected using RT-qPCR and WB assays. Cell proliferation and sphere-forming ability were detected using Cell Counting Kit-8 (CCK-8) assay, 5-Ethynyl-2'-deoxyuridine (EdU) staining, and sphere formation assay. Cell migration and invasion were detected using wound healing and transwell assay. The tube-forming ability of human umbilical vein endothelial cells (HUVEC) cells was detected using tubular formation experiments. To investigate the regulatory mechanism of ELF1, the crosstalk between ELF1 and downstream DCLK1 was predicated and verified using the JASPAR database, luciferase reporter gene, and Chromatin Immunoprecipitation (ChIP) assay.

Results: Results of the present study demonstrated that ELF1 expression was upregulated in CRC cells ( < 0.001). ELF1 silence significantly inhibited CRC cell proliferation, stemness, invasion, migration, and angiogenesis ( < 0.001). ELF1 silence also suppressed the expressions of Nanog Homeobox (Nanog), SRY-Box Transcription Factor 2 (Sox2), Octamer-Binding Transcription Factor 4 (OCT4), N-cadherin, and Vimentin while increasing the expression of E-cadherin ( < 0.001). Besides, ELF1 could positively regulate DCLK1 expression. However, the results of subsequent experiments revealed that DCLK1 overexpression partially offset the inhibitory effects of ELF1 knockdown on CRC cell proliferation, stemness, invasion, migration, and angiogenesis ( < 0.01).

Conclusion: In summary, our study provides compelling evidence that ELF1 up-regulates DCLK1 expression, thereby promoting the malignant progression and stemness of colorectal cancer. These findings significantly contribute to our understanding of the regulatory mechanisms in CRC and may have implications for future therapeutic strategies.