Roles of lncRNAs in NF-κB-Mediated Macrophage Inflammation and Their Implications in the Pathogenesis of Human Diseases.

Over the past century, molecular biology's focus has transitioned from proteins to DNA, and now to RNA. Once considered merely a genetic information carrier, RNA is now recognized as both a vital element in early cellular life and a regulator in complex organisms. Long noncoding RNAs (lncRNAs), which are over 200 bases long but do not code for proteins, play roles in gene expression regulation and signal transduction by inducing epigenetic changes or interacting with various proteins and RNAs. These interactions exhibit a range of functions in various cell types, including macrophages. Notably, some macrophage lncRNAs influence the activation of NF-κB, a crucial transcription factor governing immune and inflammatory responses. Macrophage NF-κB is instrumental in the progression of various pathological conditions including sepsis, atherosclerosis, cancer, autoimmune disorders, and hypersensitivity. It orchestrates gene expression related to immune responses, inflammation, cell survival, and proliferation. Consequently, its malfunction is a key contributor to the onset and development of these diseases. This review aims to summarize the function of lncRNAs in regulating NF-κB activity in macrophage activation and inflammation, with a particular emphasis on their relevance to human diseases and their potential as therapeutic targets. The insights gained from studies on macrophage lncRNAs, as discussed in this review, could provide valuable knowledge for the development of treatments for various pathological conditions involving macrophages.

Role of Macrophage lncRNAs in Mediating Inflammatory Processes in Atherosclerosis and Sepsis.

Long noncoding RNAs (lncRNAs) are molecules >200 bases in length without protein-coding functions implicated in signal transduction and gene expression regulation via interaction with proteins or RNAs, exhibiting various functions. The expression of lncRNAs has been detected in many cell types, including macrophages, a type of immune cell involved in acute and chronic inflammation, removal of dead or damaged cells, and tissue repair. Increasing evidence indicates that lncRNAs play essential roles in macrophage functions and disease development. Additionally, many animal studies have reported that blockage or modulation of lncRNA functions alleviates disease severity or morbidity rate. The present review summarizes the current knowledge regarding lncRNAs expressed in macrophages, focusing on their molecular targets and the biological processes regulated by them during the development of inflammatory diseases such as atherosclerosis and sepsis. Possible application of this information to lncRNA-targeting therapy is also discussed. The studies regarding macrophage lncRNAs described in this review can help provide valuable information for developing treatments for various pathological conditions involving macrophages.

Macrophage lncRNAs in cancer development: Long-awaited therapeutic targets.

In the tumor microenvironment, the interplay among macrophages, cancer cells, and endothelial cells is multifaceted. Tumor-associated macrophages (TAMs), which often exhibit an M2 phenotype, contribute to tumor growth and angiogenesis, while cancer cells and endothelial cells reciprocally influence macrophage behavior. This complex interrelationship highlights the importance of targeting these interactions for the development of novel cancer therapies aimed at disrupting tumor progression and angiogenesis. Accumulating evidence underscores the indispensable involvement of lncRNAs in shaping macrophage functionality and contributing to the development of cancer. Animal studies have further validated the therapeutic potential of manipulating macrophage lncRNA activity to ameliorate disease severity and reduce morbidity rates. This review provides a survey of our current understanding of macrophage-associated lncRNAs, with a specific emphasis on their molecular targets and their regulatory impact on cancer progression. These lncRNAs predominantly govern macrophage polarization, favoring the dominance of M2 macrophages or TAMs. Exosomes or extracellular vesicles mediate lncRNA transfer between macrophages and cancer cells, affecting cellular functions of each other. Moreover, this review presents therapeutic strategies targeting cancer-associated lncRNAs. The insights and findings presented in this review pertaining to macrophage lncRNAs can offer valuable information for the development of treatments against cancer.