LncRNA TYMSOS facilitates breast cancer metastasis and immune escape through downregulating ULBP3

Zhang, Kejing; Tan, Xiao-Lang; Guo, Lei

doi:10.1016/j.isci.2023.107556

Cited by 4 publications

(3 citation statements)

References 25 publications

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“…As demonstrated by a previous study, ULBP3 can influence immune escape phenomena. 17 Thereafter, we also examined the impact of ULBP3 on the cytotoxicity of NK cells, we employed IL‐2‐stimulated HCC cells. Co‐culturing NK92 cells with ULBP3 overexpression cells revealed noteworthy results.…”

Section: Resultsmentioning

confidence: 99%

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Unveiling the role of the KLF4/Lnc18q22.2/ULBP3 axis in the tumorigenesis and immune escape of hepatocellular carcinoma under hypoxic condition

Wei,

He,

Tan

et al. 2024

J Cellular Molecular Medi

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Hepatocellular carcinoma (HCC) represents a significant global health burden, necessitating an in‐depth exploration of its molecular underpinnings to facilitate the development of effective therapeutic strategies. This investigation delves into the complex role of long non‐coding RNAs (lncRNAs) in the modulation of hypoxia‐induced HCC progression, with a specific emphasis on delineating and functionally characterizing the novel KLF4/Lnc18q22.2/ULBP3 axis. To elucidate the effects of hypoxic conditions on HCC cells, we established in vitro models under both normoxic and hypoxic environments, followed by lncRNA microarray analyses. Among the lncRNAs identified, Lnc18q22.2 was found to be significantly upregulated in HCC cells subjected to hypoxia. Subsequent investigations affirmed the oncogenic role of Lnc18q22.2, highlighting its critical function in augmenting HCC cell proliferation and migration. Further examination disclosed that Kruppel‐like factor 4 (KLF4) transcriptionally governs Lnc18q22.2 expression in HCC cells, particularly under hypoxic stress. KLF4 subsequently enhances the tumorigenic capabilities of HCC cells through the modulation of Lnc18q22.2 expression. Advancing downstream in the molecular cascade, our study elucidates a novel interaction between Lnc18q22.2 and UL16‐binding protein 3 (ULBP3), culminating in the stabilization of ULBP3 protein expression. Notably, ULBP3 was identified as a pivotal element, exerting dual functions by facilitating HCC tumorigenesis and mitigating immune evasion in hypoxia‐exposed HCC cells. The comprehensive insights gained from our research delineate a hitherto unidentified KLF4/Lnc18q22.2/ULBP3 axis integral to the understanding of HCC tumorigenesis and immune escape under hypoxic conditions. This newly unveiled molecular pathway not only enriches our understanding of hypoxia‐induced HCC progression but also presents novel avenues for therapeutic intervention.

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Section: Resultsmentioning

confidence: 99%

“…As demonstrated by a previous study, ULBP3 can influence immune escape phenomena. 17 those effects were aborted by ULBP3 overexpression. These results suggest that KLF4 plays an oncogenic role in HCC progression through regulating Lnc18q22.2/ULBP3 axis under hypoxic conditions.…”

Section: Ulbp3 Regulates Hcc Tumorigenic Properties and Immune Escape...mentioning

confidence: 99%

Unveiling the role of the KLF4/Lnc18q22.2/ULBP3 axis in the tumorigenesis and immune escape of hepatocellular carcinoma under hypoxic condition

Wei,

He,

Tan

et al. 2024

J Cellular Molecular Medi

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show abstract

“…The dysregulated lncRNAs in NKs were closely associated with the cytotoxicity and differentiation of NKs. LncRNA TYMSOS has been shown to promote immune escape and repress the NK92 cells cytotoxicity in breast cancer [80]. Knocking down of lncRNA MALAT1 significantly boosted NK cells-mediated killing and CD8+ T cells-mediated cytotoxicity in TNBC cells [81].…”

Section: Natural Killer Cells (Nks)mentioning

confidence: 99%

Long Non-Coding RNAs as Regulators for Targeting Breast Cancer Stem Cells and Tumor Immune Microenvironment: Biological Properties and Therapeutic Potential

Yang,

Qiu

et al. 2024

Cancers

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Breast cancer stem cells (BCSCs) is a subpopulation of cancer cells with self-renewal and differentiation capacity, have been suggested to give rise to tumor heterogeneity and biologically aggressive behavior. Accumulating evidence has shown that BCSCs play a fundamental role in tumorigenesis, progression, and recurrence. The development of immunotherapy, primarily represented by programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors, has greatly changed the treatment landscape of multiple malignancies. Recent studies have identified pervasive negative associations between cancer stemness and anticancer immunity. Stemness seems to play a causative role in the formation of cold tumor immune microenvironment (TIME). The multiple functions of long non-coding RNAs (lncRNAs) in regulating stemness and immune responses has been recently highlighted in breast cancer. The review focus on lncRNAs and keys pathways involved in the regulation of BCSCs and TIME. Potential clinical applications using lncRNAs as biomarkers or therapies will be discussed.

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Potential therapies for non-coding RNAs in breast cancer

Li,

Ji,

et al. 2024

Front. Oncol.

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Breast cancer (BC) is one of the frequent tumors that seriously endanger the physical and mental well-being in women with strong heterogeneity, and its pathogenesis involves multiple risk factors. Depending on the type of BC, hormonal therapy, targeted therapy, and immunotherapy are the current systemic treatment options along with conventional chemotherapy. Despite significant progress in understanding BC pathogenesis and therapeutic options, there is still a need to identify new therapeutic targets and develop more effective treatments. According to recent sequencing and profiling studies, non-coding (nc) RNAs genes are deregulated in human cancers via deletion, amplification, abnormal epigenetic, or transcriptional regulation, and similarly, the expression of many ncRNAs is altered in breast cancer cell lines and tissues. The ability of single ncRNAs to regulate the expression of multiple downstream gene targets and related pathways provides a theoretical basis for studying them for cancer therapeutic drug development and targeted delivery. Therefore, it is far-reaching to explore the role of ncRNAs in tumor development and their potential as therapeutic targets. Here, our review outlines the potential of two major ncRNAs, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) as diagnostic and prognostic biomarkers as well as targets for new therapeutic strategies in breast cancer.

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LncRNA TYMSOS facilitates breast cancer metastasis and immune escape through downregulating ULBP3

Cited by 4 publications

References 25 publications

Unveiling the role of the KLF4/Lnc18q22.2/ULBP3 axis in the tumorigenesis and immune escape of hepatocellular carcinoma under hypoxic condition

Unveiling the role of the KLF4/Lnc18q22.2/ULBP3 axis in the tumorigenesis and immune escape of hepatocellular carcinoma under hypoxic condition

Long Non-Coding RNAs as Regulators for Targeting Breast Cancer Stem Cells and Tumor Immune Microenvironment: Biological Properties and Therapeutic Potential

Potential therapies for non-coding RNAs in breast cancer

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