REG4 Human

Regenerating islet-derived 4 (REG4) is a member of the regenerating (REG) protein family, which belongs to the calcium-dependent lectin (C-type lectin) gene superfamily. The REG family consists of several members, including REG1A, REG1B, REG3A, REG3G, and REG4, each playing crucial roles in various biological processes such as cell proliferation, regeneration, inflammation, and tumor formation .

REG4 was initially identified through high-throughput sequence analysis of a cDNA library derived from patients with inflammatory bowel disease . The gene encoding REG4 is located on the long arm of chromosome 1 and comprises six introns and seven exons. The protein encoded by REG4 consists of 158 amino acids, including a signal peptide of 22 amino acids and a conserved calcium-dependent hydrocarbon recognition domain (CRD) located at amino acid positions 30–155 . This CRD is critical for the biological function of REG4, particularly in promoting invasion and migration abilities .

REG4 has emerged as a multifunctional protein with various biological activities. It is known for its pro-proliferative, anti-apoptotic, differentiation-inducing, and bactericidal properties . REG4 is abnormally expressed in several types of cancers, including colorectal, gastric, gallbladder, pancreatic, ovarian, prostate, and lung cancers . It is associated with unfavorable prognostic features in these cancers, such as advanced tumor and nodal stage, histological differentiation, and liver and peritoneal metastasis . Additionally, REG4-positive cancer cells often exhibit resistance to chemoradiotherapy, particularly 5-FU-based chemotherapy .

The underlying mechanisms of REG4’s biological functions are complex and involve various signaling mediators and pathways. REG4 participates in multiple aspects of carcinogenesis, including cell proliferation, apoptosis, cell cycle regulation, invasion, metastasis, and drug resistance . The calcium-dependent hydrocarbon recognition domain (CRD) within REG4 plays a crucial role in these processes .

Due to its significant role in cancer progression and resistance to therapy, REG4 is considered a potential diagnostic and prognostic biomarker as well as a candidate therapeutic target in cancer patients . Understanding the mechanisms underlying REG4’s functions and its interactions with other cellular components is essential for developing targeted therapies and improving cancer treatment outcomes.

Despite the advances in understanding REG4’s biological functions, several challenges remain. The regulation of REG4 expression and the exact molecular mechanisms of its action are not fully understood . Additionally, the existence of multiple REG family members with significant homology and potentially compensatory functions complicates the study of individual REG proteins . Coordinated research efforts are needed to address these challenges and to explore the therapeutic potential of REG4 and other REG family members.

In conclusion, REG4 is a multifunctional protein with significant implications in cancer biology. Its role as a diagnostic and prognostic biomarker and a potential therapeutic target makes it a critical focus of ongoing research in the field of oncology.