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EZH2-interacting lncRNAs contribute to gastric tumorigenesis; a review on the mechanisms of action

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Abstract

Gastric cancer (GC) remains one of the deadliest malignancies worldwide, demanding new targets to improve its diagnosis and treatment. Long non-coding RNAs (lncRNAs) are dysregulated through gastric tumorigenesis and play a significant role in GC progression and development. Recent studies have revealed that lncRNAs can interact with histone-modifying polycomb protein, enhance Zeste Homolog 2 (EZH2), and mediate its site-specific functioning. EZH2, which functions as an oncogene in GC, is the catalytic subunit of the PRC2 complex that induces H3K27 trimethylation and epigenetically represses gene expression. EZH2-interacting lncRNAs can recruit EZH2 to the promoter regions of various tumor suppressor genes and cause their transcriptional deactivation via histone methylation. The interactions between EZH2 and this lncRNA modulate different processes, such as cell cycle, cell proliferation and growth, migration, invasion, metastasis, and drug resistance, in vitro and in vivo GC models. Therefore, EZH2-interacting lncRNAs are exciting targets for developing novel targeted therapies for GC. Subsequently, this review aims to focus on the roles of these interactions in GC progression to understand the therapeutic value of EZH2-interacting lncRNAs further.

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Authors and Affiliations

  1. Kermanshah University of medical sciences, International branch, Kermanshah, Iran

    Hossein Mohebbi

  2. Department of Medicine, Shahid Beheshti University, Tehran, Iran

    Romina Esbati & Omid Yazdani

  3. Department of Pharmacy, Al-Noor University College, Nineveh, Iraq

    Ran Abdalsalam Hamid

  4. School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    Roozbeh Akhavanfar

  5. College of Pharmacy, National University of Science and Technology, Dhi Qar, Iraq

    Usama Kadem Radi

  6. Department of Internal Medicine, Amir Alam Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Goli Siri

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HM, RE, RAH, and RA: Conceptualization, Visualization, Writing - original draft. UKR: Writing - Review & Editing, Visualization, GS and OY: Supervision. All authors reviewed the manuscript.

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Mohebbi, H., Esbati, R., Hamid, R.A. et al. EZH2-interacting lncRNAs contribute to gastric tumorigenesis; a review on the mechanisms of action. Mol Biol Rep 51, 334 (2024). https://doi.org/10.1007/s11033-024-09237-7

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