Intro
Long non-coding RNAs (lncRNAs) represent a distinct class of noncoding RNAs (ncRNAs) that exceed 200 nucleotides in length and have been found to modulate cell proliferation, apoptosis, invasiveness, drug resistance, and other pivotal biological functions. These functions can be influenced at the transcriptional, posttranscriptional, and epigenetic levels ( 1 , 2 ). Numerous investigations in recent years have underscored the critical role lncRNAs play in multiple stages of disease pathogenesis ( 3 ). Among the early identified lncRNAs, lncRNA H19 has been garnering significant interest across a variety of disciplines. This review provides a comprehensive overview of the characteristics and recent advancements in research pertaining to lncRNA H19 in the field of gynecology.
Other
lncRNAs have gained significant attention for their wide-ranging roles in gene regulation, cellular functions and disease etiology. Among the multitude of lncRNAs under rigorous examination, lncRNA H19 stands out due to its multifaceted involvement in immune response modulation across various pathological contexts. In gastric cancer (GC), a highly prevalent malignancy, lncRNA H19 has been found to regulate immune cell infiltration via miR-378a-5p/SERPINH1 signaling ( 115 ). This mechanism is believed to contribute significantly to GC progression, highlighting the dynamic interaction between H19 and immune cells. Moreover, lncRNA H19 has been implicated in the regulation of aerobic glycolysis and cell proliferation, serving an instrumental role in immune evasion in GC cells via the miR-519d-3p/lactate dehydrogenase A axis ( 48 ). Markedly, research has indicated that knocking down H19 can reduce the immunosuppressive effect of GC cells, suggesting a promising therapeutic avenue ( 48 ). Further emphasizing the immune-related effects of lncRNA H19 is its role in thyroid carcinoma (THCA). lncRNA H19 has been found to be differentially expressed in THCA, with its expression associated with immune cell infiltration in the disease. Specifically, it was found to be positively correlated with the infiltration level of various immune cells such as CD4+ T cells, CD8+ T cells, B cells, dendritic cells, neutrophils and macrophages. Moreover, lncRNA H19 was associated with multiple immune markers, underscoring its potential role in shaping the immune landscape of THCA ( 116 ).
In the context of systemic lupus erythematosus (SLE), an autoimmune disease, lncRNA H19 exhibits a significant upregulation and is associated with immune dysregulation in bone marrow-derived mesenchymal stem cells (BMMSCs) ( 117 ). The mechanism, notably, involves H19 inhibiting the production of the interleukin-2 cytokine, an important modulator of immune responses. This finding not only broadens the known landscape of lncRNA H19-mediated immunomodulation but also positions H19 as a potential therapeutic target for SLE. Beyond its association with cancer and autoimmune disease, lncRNA H19 also serves a critical role in mammary epithelial cells. Overexpression of lncRNA H19 promotes cell proliferation and enhances the expression of proteins related to cell structure and function, such as β-casein and tight junction-related proteins ( 118 ). Furthermore, it influences immune responses by increasing the expression of inflammatory factors [TNF-α, interleukin 6, chemokine (C-X-C motif) ligand 2 and chemokine (C-C motif) ligand 5] and activating the NF-κB signal pathway, thus potentially linking H19 to inflammatory disorders of the breast, including mastitis and possibly even breast cancer ( 118 , 119 ).
Overall, the effect of lncRNA H19 on immune regulation is diverse and context-dependent, with its involvement in a wide range of diseases and cellular functions. A recurring theme in the literature is the relationship between lncRNA H19 and inflammatory responses. lncRNA H19 has been associated with heightened inflammation, frequently observed in diseases such as endometriosis and ovarian cancer, probably by modulating immune response genes and regulating cytokine production. The upregulation of lncRNA H19 perpetuates an inflammatory microenvironment, favoring disease progression through several mechanisms including promoting cytokine production, fostering immune cell recruitment and proliferation and enhancing expression of inflammatory genes ( 120 ). The potential value of lncRNA H19 as a therapeutic target to dampen excessive inflammation, offering potential treatment avenues for inflammatory gynecological conditions.
The effect of H19 on the immune response and gynecological diseases does not exist in isolation. The intricate network of microRNAs, epigenetic modifications and signal transduction pathways form a convoluted regulatory network with H19 at the center ( 121 , 122 ). The functionality of this network depends on a delicate balance, the disturbance of which can lead to pathological states ( 37 , 120 ). Consequently, a comprehensive understanding of these interactions is key for the development of effective therapeutic strategies targeting lncRNA H19 ( 37 ). However, despite the wealth of evidence linking lncRNA H19 with immune regulation, the precise mechanisms through which lncRNA H19 exerts its effects remain to be elucidated. The inherent complexities of lncRNAs, combined with the multifaceted nature of immune responses, present challenges to fully elucidating the roles of H19 in gynecological disease pathogenesis ( 123 ). Future studies, perhaps employing advanced techniques such as single-cell RNA sequencing and high-throughput chromatin conformation capture, could aid in painting a more comprehensive picture of H19's functional role in these diseases.
Conclusions
In summary, the lncRNA H19 has been discerned to serve a critical role in the etiology of diverse benign and malignant pathologies in gynecological health, employing a multiplicity of mechanisms. This molecular entity holds promise as an efficacious biomarker for early-stage detection and prognostic assessment of gynecological conditions, while also potentially offering a novel avenue for therapeutic intervention. However, the existing body of research concerning lncRNA H19 in the realm of gynecology is still in its nascent stage and the intricate role that H19 serves in disease initiation, advancement and modulation of the immune milieu in gynecology remains predominantly elusive.
Therefore, it is imperative that the labyrinthine regulatory network of lncRNA H19 be further elucidated, particularly in the context of its influence on various gynecological diseases. Advancements in cellular and molecular biology, coupled with cutting-edge gene technology, pave the way for this endeavor. Moreover, the execution of additional clinical and fundamental experiments, utilizing larger sample sizes, will augment our understanding of the functionality and mechanistic underpinnings of lncRNA H19 in gynecological diseases. In turn, this acquired knowledge can expedite the evolution of diagnostic procedures and therapeutic strategies in gynecology, thereby elevating patient care standards.