Fibrillarin and fibrillarin-like their role in cancer progression: new approaches and perspectives.

Fibrillarin (FBL), a highly conserved nucleolar 2′-O-methyltransferase, is essential for pre-rRNA processing, ribosome biogenesis, and nucleolar organization. Recent evidence demonstrates that FBL also plays broader roles in cancer biology, influencing oncogenic translation, RNA epigenetic regulation, genomic stability, and the DNA damage response. In this review, we integrate transcriptomic analyses from multiple types of cancer, with experimental findings showing that FBL is frequently dysregulated and often overexpressed in tumors such as breast, liver, lung, prostate cancer, and acute myeloid leukemia. These alterations correlate with increased proliferation, metabolic reprogramming, nucleolar stress adaptation, and poor clinical outcomes. Furthermore, we discuss how post-translational modifications and specific molecular interactors modulate FBL function and contribute to tumor progression. We also highlight the emerging relevance of Fibrillarin-like protein 1 (FBLL1), a structural paralog of FBL whose biological functions remains to be understood. FBLL1 was initially found in neuronal RNA modification, recent data indicate that FBLL1 may also be altered in some particular types of cancer. By examining unique and shared interactors of FBL and FBLL1, we provide an updated perspective on their potential complementary roles in nucleolar regulation and tumorigenesis. Overall, current evidence positions FBL and potentially FBLL1 as promising biomarkers and regulatory hubs in cancers with elevated nucleolar activity. Further studies are required to define their therapeutic potential and mechanistic contributions to malignancy.