Zinc Finger Proteins: Functions and Mechanisms in Colon Cancer

SIMPLE SUMMARY: Over the past few decades, despite advances in colon cancer surgery, the pro-gnosis of late colon cancer patients with liver metastasis remains poor. Currently, its incidence ranks second in men and third in women. Fortunately, accumulating evidence has unraveled that zinc finger proteins (ZFPs) will shed light on the treatment of colon cancer. As the largest transcription family in the human genome, ZFPs are a class of transcription factors that can bind Zn(2+), self-fold to form “finger” domains and regulate the expression of target genes. In this article, we elucidate the specific molecular mechanisms of ZFPs that are well-suited to orchestrate pathophysiological changes in colon cancer development, which may lay a credible foundation for further precision oncology. ABSTRACT: According to the global cancer burden data for 2020 issued by the World Health Organization (WHO), colorectal cancer has risen to be the third-most frequent cancer globally after breast and lung cancer. Despite advances in surgical treatment and chemoradiotherapy for colon cancer, individuals with extensive liver metastases still have depressing prognoses. Numerous studies suggest ZFPs are crucial to the development of colon cancer. The ZFP family is encoded by more than 2% of the human genome sequence and is the largest transcriptional family, all with finger-like structural domains that could combine with Zn(2+). In this review, we summarize the functions, molecular mechanisms and recent advances of ZFPs in colon cancer. We also discuss how these proteins control the development and progression of colon cancer by regulating cell proliferation, EMT, invasion and metastasis, inflammation, apoptosis, the cell cycle, drug resistance, cancer stem cells and DNA methylation. Additionally, several investigations have demonstrated that Myeloid zinc finger 1 (MZF1) has dual functions in colon cancer, which may both promote cancer proliferation and inhibit cancer progression through apoptosis. Generally, a comprehensive understanding of the action mechanisms of ZFPs in colon cancer will not only shed light on the discovery of new diagnostic and prognosis indicators but will also facilitate the design of novel targeted therapies.