The mechanism of LncRNA regulating ubiquitination and its research progression in cancer

Long non-coding RNAs (LncRNAs) are a class of RNA molecules that surpass 200 nucleotides in length, distinguished by the absence of an open reading frame and primarily transcribed by RNA polymerase Ⅱ. LncRNAs have been demonstrated to play pivotal roles in epigenetic regulation, gene expression modulation, and protein post-translational modifications. Ubiquitination, a critical post-translational modification mechanism, regulates protein stability, activity and degradation by changing intracellular target proteins. A plethora of biological activities, encompassing cell signaling pathways, metabolic reprogramming, immunological evasion and oncogenesis, are intricately linked to the ubiquitination process. Research has demonstrated that LncRNAs influence the process by modulating ubiquitinases and engaging with substrate proteins or deubiquitinases. For instance, LncRNAs have been shown to function as molecular scaffolding to help ubiquitinated complexes form or directly interact with ubiquitinases to modulate their catalytic activity, stabilizing and inhibiting target protein ubiquitination. By activating signaling pathways or repressing tumor suppressors such as p53, LncRNAs can help or hinder cancer cells proliferation. Furthermore, certain LncRNAs have been found to regulate the ubiquitination of immune-related molecules or metabolic enzymes inside the tumor microenvironment, thus facilitating cancer ' s evasion of immune surveillance or modifying energy metabolism to enhance the survival and dissemination of cancer cells. The present review aims to elucidate how LncRNAs influence protein ubiquitination and their roles in cancer, thereby providing new insights into searching mechanisms of cancer development and screening the therapeutic targets.