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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1506561
This article is part of the Research Topic Interplay of Epigenetic Regulation and Cellular Metabolism in Cancer Microenvironments View all 3 articles

Global lncRNA expression signature in pre-metastatic lung and their regulatory effects in pulmonary metastasis

Provisionally accepted
Huifang Shi Huifang Shi 1,2Peng Wang Peng Wang 3*Jiaan Wang Jiaan Wang 1*Lei Chen Lei Chen 1*Yan Qin Yan Qin 1*Jie Lv Jie Lv 1*
  • 1 People’s Hospital of Rizhao, Rizhao, China
  • 2 Clinical Laboratory, The Rizhao People’s Hospital Affiliated to Jining Medical University, Rizhao, China
  • 3 Clinical Laboratory, Rizhao Center for Disease Control and Prevention, Rizhao, China

The final, formatted version of the article will be published soon.

    Background Lung metastasis has garnered significant attention due to its prevalent occurrence. Pre-metastatic niche (PMN) establishment is a critical prerequisite for the onset of lung metastasis. Emerging evidence indicates that long noncoding RNAs (lncRNAs) play pivotal roles in the metastatic cascade to the lungs. However, the relationship between lncRNA expression profiles and the formation of PMN remains uncharacterized. This study aims to explore the expression profiles and potential roles of lncRNAs in the context of pre-metastatic lung microenvironment.Methods RNA sequencing was utilized to elucidate the lncRNA landscape in pre-metastatic lung of murine models. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to infer the prospective functions of the differentially expressed lncRNAs. Among these, lncRNA Gm5144-202 in alveolar macrophages (AMs) was further scrutinized for its role in driving M2 macrophage polarization, facilitating the formation of PMN, and orchestrating the apoptosis, proliferation, and migration of tumor cells in vitro.Results A total of 232 lncRNAs exhibited differential expression in pre-metastatic murine lungs compared to normal controls, predominantly enriching pathways such as PI3K-Akt signaling, calcium signaling, neuroactive ligand-receptor interaction, and NF-B signaling.Notably, lncRNA Gm5144-202 exhibited the most pronounced difference, with elevated level in alveolar macrophages (AMs) during the pre-metastatic phase. Silencing of lncRNA Gm5144-202 impeded the polarization of M2-like macrophages, suppressed the expression of factors critical for the formation of the PMN, and inhibited tumor cell invasion.Our research delineated the lncRNA expression profiles in pre-metastatic pulmonary tissues and identified, for the first time, the pivotal role of lncRNA Gm5144-202 in modulating M2 macrophage polarization and tumor cell invasiveness. Consequently, targeting lncRNA Gm5144-202 holds substantial promise for translational applications aimed at mitigating pulmonary metastasis.

    Keywords: Pre-metastatic niche, lncRNAs, alveolar macrophage, M2 polarization, metastasis

    Received: 05 Oct 2024; Accepted: 13 Nov 2024.

    Copyright: © 2024 Shi, Wang, Wang, Chen, Qin and Lv. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Peng Wang, Clinical Laboratory, Rizhao Center for Disease Control and Prevention, Rizhao, China
    Jiaan Wang, People’s Hospital of Rizhao, Rizhao, China
    Lei Chen, People’s Hospital of Rizhao, Rizhao, China
    Yan Qin, People’s Hospital of Rizhao, Rizhao, China
    Jie Lv, People’s Hospital of Rizhao, Rizhao, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.