The Roles of the Canonical Members of Ribonuclease A Family in Tumorigenesis / 中国生物化学与分子生物学报

ABSTRACT

In human, the ribonuclease A (RNase A) family contains 8 canonical members (RNase 1-RNase 8). Research evidence indicated that all the canonical members of this family, except RNase 8, are involved in the occurrence and development of a variety of tumors, including pancreatic cancer, colorectal cancer, bladder cancer, breast cancer, and skin cancer, etc. During tumorigenesis, the expression of specific RNase increased and glycosylation modifications changed, which are potential markers for tumor diagnosis; They also participate in tumor initiation, growth, and metastasis with a variety of mechanisms, and are potential targets for tumor therapy; Meanwhile, some members have the function of killing tumor cells and inhibiting tumor development, and it is possible to develop into tumor therapeutic drugs. Concretely, RNase 1 suppresses tumor growth by directly killing tumor cells or reducing local inflammation through its ribonuclease activity-dependent cytotoxicity and extracellular RNA degradation functions; however, its binding and activation of ephrin A4 signaling pathway promotes breast cancer initiation. RNase 2 and RNase 3 are important components of eosinophil granule proteins that play an important role in anti-tumor immune defense, and their function of killing tumor cells depends on both cationic nature and ribonuclease activity. RNase 4 and RNase 5 can promote tumorigenesis by inducing angiogenesis, promoting tumor cell proliferation, and inhibiting tumor cell apoptosis. The molecular mechanisms of RNase 5 action include promoting the transcription of 47 S precursor rRNA, activating signaling pro-tumor growth signaling pathways, and generating tRNA-derived stress-induced RNA (tiRNA). Besides, RNase 6 and RNase 7 are related to the occurrence of tumors thought their specific role and mechanism are still unclear. In this review, we summarized the relevance and mechanism of RNase A family members on promoting or inhibiting tumors and analyzed their clinical application potentials.