Colorectal cancer (CRC) has been ranked as the third most prevalent cancer worldwide. Indeed, it represents 10.2% of all cancer cases. It is also the second most common cause of cancer mortality, and accounted for about 9.2% of all cancer deaths in 2018. Early detection together with a correct diagnosis and staging remains the most effective clinical strategy in terms of disease recovery. Thanks to advances in diagnostic techniques, and improvements of surgical adjuvant and palliative therapies, the mortality rate of CRC has decreased by more than 20% in the last decade. Cancer biomarkers for the early detection of CRC, its management, treatment and follow-up have contributed to the decrease in CRC mortality. Herein, we provide an overview of molecular biomarkers from tumor tissues and liquid biopsies that are approved for use in the CRC clinical setting for early detection, follow-up, and precision therapy, and of biomarkers that have not yet been officially validated and are, nowadays, under investigation.

The zinc finger protein ZNF224 plays a dual role in cancer, operating as both tumor suppressor and oncogenic factor depending on cellular and molecular partners. In this research we investigated the role of ZNF224 in melanoma, a highly invasive and metastatic cancer, and provided evidence for the involvement of ZNF224 in the TGF-β signaling as a mediator of the TGF-β pro-oncogenic function. Our results showed that ZNF224, whose expression increased in melanoma cell lines after TGF-β stimulation, potentiated the activation induced by TGF-β on its target genes involved in epithelial-mesenchymal transition (EMT). Accordingly, overexpression of ZNF224 enhanced the tumourigenic properties of melanoma cells, promoting cell proliferation and invasiveness, while ZNF224 knockdown had the opposite effect. Moreover, ZNF224 positively modulates the expression of TGF-β itself and its type 1 and 2 receptors (TβR1 and TβR2), thus highlighting a possible mechanism by which ZNF224 could enhance the endogenous TGFβ/Smad signalling. Our findings unveil a positive regulatory loop between TGF-β and ZNF224 to promote EMT, consequently increasing the tumour metastatic potential.

Background: The zinc finger protein ZNF224 plays a dual role in human cancers, operating as both tumour suppressor and oncogenic factor depending on the cellular context and molecular partners. In this research, we investigated the role played by ZNF224 in the TGF-β signalling in malignant melanoma. Methods: Real-time qPCR, western blot, and chromatin immunoprecipitation assays were performed to examine the molecular mechanisms of ZNF224 in TGF-β signalling in melanoma. ZNF224-induced cell anchorage, independent growth, migration, and invasion were assessed by the colony formation, wound healing, and transwell assays.Results: Our findings showed that ZNF224, whose expression increased in melanoma cell lines after TGF-b stimulation, potentiated the activation induced by TGF-β on its target genes involved in epithelial-mesenchymal transition (EMT). Accordingly, overexpression of ZNF224 improved the tumourigenic properties of melanoma cells, promoting cell proliferation and invasiveness, while ZNF224 knockdown had the opposite effect. Moreover, ZNF224 promoted the transcriptional activation of TGF-β itself and its type 1 and 2 receptors (TβR1 and TβR2), thus highlighting a possible mechanism by which ZNF224 could enhance the endogenous TGFβ/Smad signalling. Conclusions: Our results provide evidence for the involvement of ZNF224 in TGF-β signalling as a mediator of TGF-β pro-oncogenic function and unveil a positive regulatory loop between TGF-β and ZNF224 to promote EMT, consequently increasing the tumour metastatic potential.