Egr‑1 inhibits colon cancer cell proliferation, migration and invasion via regulating CDKL1 at the transcriptional level

Abstract

Colon cancer is one of the most common malignant tumors worldwide, and the molecular mechanisms involved in the oncogenesis and progression of colon cancer remain unclear. Early growth response 1 (Egr-1) is a transcription factor that is closely associated with several tumor processes; however, its role in colon cancer is unknown. The present study aimed to explore the function and mechanism of transcription factor Egr-1 in colon cancer progression. The association between Egr-1 expression and the survival of patients with colon cancer was analyzed. Transwell assay was used to measure the migration and invasion of colon cancer cells. Cell Counting Kit-8 assay was used to evaluate the cell proliferative ability. Reverse transcription-quantitative PCR and western blot assays were used to identify whether Egr-1 could regulate cyclin-dependent kinase-like 1 (CDKL1). Luciferase and chromatin immunoprecipitation assays were used to detect the mechanism by which Egr-1 regulated CDKL1. Based on The Cancer Genome Atlas database, it was found that low Egr-1 expression was associated with a poor prognosis in patients with colon cancer. Furthermore, overexpression of Egr-1 inhibited colon cancer cell proliferation, migration, and invasion, whereas knockdown of Egr-1 increased colon cancer cell proliferation, migration and invasion. Additionally, overexpression of Egr-1-induced cell proliferation, migration and invasion were reversed by overexpression of CDKL1. Furthermore, it was demonstrated that Egr-1 regulated CDKL1 expression at the transcriptional level. The present study illustrated the mechanism of Egr-1 regulating CDKL1, by which Egr-1 affected colon cancer cell proliferation, migration and invasion. The current findings suggested that Egr-1/CDKL1 may be a new promising target for the treatment of colon cancer.

EGR1 Enhances Lymphangiogenesis via SOX18-Mediated Activation of JAK2/STAT3 Pathway

“…EGR1 has been considered as a therapeutic target for multiple diseases, such as prostate cancer, lymphoid tumors, Alzheimer's disease, and diabetes [ 10 – 13 ]. EGR1 plays a vital role in many biological programs, including cell survival, cell death, apoptosis, cell motility, and metastasis [ 9 , 14 , 15 ]. EGR1 is demonstrated to have a critical role in angiogenesis as well.…”

Computational Recognition of a Regulatory T-cell-specific Signature With Potential Implications in Prognosis, Immunotherapy, and Therapeutic Resistance of Prostate Cancer

“…Early growth response-1 (EGR1) is a transcription factor involved in cell proliferation and in the regulation of apoptosis. Several previous studies showed that EGR1 exhibits prominent tumor suppressor function in glioma (44), non-smallcell lung cancer (45), colon cancer (46), papillary thyroid carcinoma (47), and breast cancer (48). Saha et al indicated that low levels of EGR1 expression were positively correlated with poor survival for RFS and distant metastasis-free survival (DMFS) in breast cancer (49).…”

miR‑let‑7c‑3p targeting on Egr‑1 contributes to the committed differentiation of leukemia cells into monocyte/macrophages

“…The Egr-1 gene, as a member of the zinc finger structure transcription factor family, is located on human chromosome 5q31 and encodes a DNA-binding transcription factor of ~80 kDa (39). It has been demonstrated that Egr-1 serves an important role in cell growth, differentiation and apoptosis (16,(40)(41)(42)(43)(44). At the same time, Egr-1 is closely associated with the occurrence and development of certain diseases, for example tutor and leukemia, however the specific signaling pathway of each of them remains to be elucidated.…”

“…It is the superiority of the aforementioned induced differentiation therapy that has made differentiation induction a research hotspot in recent years (12)(13)(14)(15). Expression of early growth response-1 (Egr-1) is a member of the early growth response protein family, which has been considered to be of great significance in a variety of physiological processes and has been extensively studied (16,17), especially in cell proliferation, angiogenesis, invasion and immune response of tumors (18,19). Egr-1 can act as a transcriptional regulator by combining the C2H2 type zinc finger with the DNA motif of the 5'-GCG(T/G)GGGCG-3' sequence.…”

“…Regardless of the methylation status of cytosine, it can bind to double-stranded target DNA and the target DNA that does not bind to cytosine is oxidized to 5-formylcytosine or 5-carboxycytosine (20,21). As it is an important part of certain signal pathways in the process of cell signal transduction, it can mediate the coupling of intracellular signal cascades and regulate the transcription and transcription of a number of downstream long-term response genes that determine cell karyotype changes (16,17). To a certain extent, the role of Egr-1 in cell proliferation and differentiation is heterogeneous, especially in normal somatic cells and malignant tumor cells.…”