Long non-coding RNAs as immune landscape regulators in cancer: A spotlight on HEIH in immuno-oncology

The dynamic interplay between cancer and the immune system is a critical determinant of tumor progression and response to therapy. Immune modulation in the tumor microenvironment can have a substantial impact on cancer progression, metastasis, and the effectiveness of conventional and new generation of immunotherapeutic interventions. Long non-coding RNAs (lncRNAs) are non-coding RNAs of 200 nucleotides in length, which might be linear or circular in structure. They are critical regulators of gene expression and cellular functions, playing essential roles in both physiological and pathological processes. Recent studies on lncRNAs have emphasized their critical role in regulating several human malignancies through a wide range of intertwined molecular processes, tuning tumor growth, metastasis, immune modulation, and many other processes. Among these, hepatocellular carcinoma upregulated EZH2-associated lncRNA (HEIH), an intergenic lncRNA, has emerged as a notable oncogene, demonstrating elevated expression levels in multiple cancers. Its oncogenic properties are largely attributed to its ability to influence key signaling pathways and enhance tumor cell proliferation and survival. However, HEIH's novel immunomodulatory role has not been well studied. The main goal of the current review is to clarify the role of lncRNAs in cancer progression, particularly by shedding light on their novel immunomodulatory role. Moreover, this review showed a special focus on HEIH's role in various malignancies, with an emphasis on its dual oncological and immunomodulatory functions and crystalizes its role as promising therapeutic target in oncology.