Ro60, also known as SSA2, is an RNA-binding protein and a core component of nucleocytoplasmic ribonucleoprotein (RNP) complexes. It is essential in RNA metabolism, cell stress response pathways, and cellular homeostasis. Ro60 stabilizes and mediates the quality control and cellular distribution of small RNAs like YRNAs, retroelement transcripts, and misfolded RNAs [1].

In autoimmune diseases, Ro60 transcriptional dysregulation or loss of function can lead to the generation and release of RNA fragments from YRNAs and other small RNAs. These fragments can trigger an inflammatory cascade through endosomal toll-like receptors (TLRs) and cytoplasmic RNA sensors, which usually sense pathogen-associated molecular patterns. This recognition can activate inflammatory response pathways and break self-tolerance. Autoreactive B cells may produce antibodies targeting extracellular Ro60 RNP complexes. Anti-Ro60 autoantibodies serve as diagnostic markers for various autoimmune diseases, such as Sjögren's disease (SjD) and systemic lupus erythematosus (SLE), and may also predict anti-drug antibody responses among rheumatic patients [1]. In pancreatic ductal adenocarcinoma, knockdown of Ro60 by siRNA transfection significantly decreased cell proliferation and invasion in vitro and inhibited the growth of subcutaneous tumors in vivo, indicating its role in promoting cancer progression [2].

In conclusion, Ro60 is crucial for RNA-related functions in normal cellular processes. Its dysregulation is associated with autoimmune diseases and cancer. The study of Ro60, especially through loss-of-function experiments like siRNA-mediated knockdown, helps to understand its role in disease-related biological processes, providing potential insights for disease diagnosis, prediction, and treatment.