Oncogenic lncRNA downregulates cancer cell antigen presentation and intrinsic tumor suppression

Hu, Qingsong; Ye, Youqiong; Chan, Li-Chuan; Li, Yajuan; Liang, Ke; Lin, Aifu; Egranov, Sergey D.; Zhang, Yaohua; Xia, Weiya; Gong, Jing; Pan, Yinghong; Chatterjee, Satabdi; Yao, Jun; Evans, Kurt W.; Nguyen, Tina K.; Park, Peter K.; Liu, Jiewei; Coarfa, Cristian; Donepudi, Sri Ramya; Putluri, Vasanta; Putluri, Nagireddy; Sreekumar, Arun; Ambati, Chandrashekar R.; Hawke, David H.; Marks, Jeffrey R.; Gunaratne, Preethi H.; Caudle, Abigail S.; Şahin, Ayşegül; Hortobágyi, Gabriel N.; Meric‐Bernstam, Funda; Chen, Lieping; Yu, Dihua; Hung, Mien‐Chie; Curran, Michael A.; Han, Leng; Lin, Chunru; Yang, Liuqing

doi:10.1038/s41590-019-0400-7

Cited by 282 publications

(262 citation statements)

References 60 publications

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“…LncRNAs target the immune checkpoints and cytokines and promote the formation of the immunosuppressive microenvironment, which contributes to tumor progression and drug resistance. Specifically, lncRNAs are emerging new therapeutic targets and prognostic biomarkers for tissue-and clinical stage-specific cancers (26,27).…”

Section: Lncrnas As Promising Therapeutic Targets and Biomarkers Formentioning

confidence: 99%

“…For example, Lnc-BM (a lncRNA related to breast cancer brain metastasis), binds to JAK2 and modulates its kinase activity through the Lnc-BM/JAK2/STAT3/ICAM1 pathway (35). Similarly, long intergenic non-coding RNA for kinase activation (LINK-A), interacts with PtdIns(3,4,5) P3 and affects the activation of the AKT pathway in the breast cancer cells (26). LncRNAs play a critical role in the epigenetic and transcriptional regulation of gene expression by interacting with the chromatin (complexes that contain proteins and DNA molecules) within the nucleus.…”

Section: Features and Functional Modules Of Lncrnas In Tumor Immune Rmentioning

confidence: 99%

“…Additionally, LINK-A can predict poor prognosis in patients with breast cancers (83,84). Hu et al demonstrated that the expression of LINK-A was negatively associated with the abundance of APCs and CD8 + T cells in the basal-like breast cancers, which indicated a correlation between LINK-A and immunosuppression (26). In the transgenic MMTV-Tg (LINK-A) mouse model, LINK-A functions as an oncogenic lncRNA and initiate metastatic mammary gland tumors, which phenotypically resembled the human TNBC.…”

Section: Expression Of Molecules In Tumor Cellsmentioning

confidence: 99%

“…In the transgenic MMTV-Tg (LINK-A) mouse model, LINK-A functions as an oncogenic lncRNA and initiate metastatic mammary gland tumors, which phenotypically resembled the human TNBC. Moreover, LINK-A could enhance the polyubiquitination-mediated degradation of the PLC components and tumor suppressors (Rb and p53) through the inhibitory GPCRs/PKA pathway (26). Treatment with the locked nucleic acids (LNAs) of LINK-A or GPCR antagonists in vivo increased the stability of MHC class I complexes and PLC components.…”

Section: Expression Of Molecules In Tumor Cellsmentioning

confidence: 99%

“…Furthermore, lncRNAs involved in the regulation of antigen presentation may potentially serve as therapeutic targets in tumor vaccines. In the mouse models of breast cancer, LINK-A expression was induced in mammary gland tumors (26). The inhibition of LINK-A expression suppressed the tumor progression.…”

Section: The Preclinical and Clinical Applications Of Lncrnas In Cancmentioning

confidence: 99%

See 4 more Smart Citations

Long Non-coding RNAs: Emerging Roles in the Immunosuppressive Tumor Microenvironment

Luo

Yang

et al. 2020

Front. Oncol.

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Section: Lncrnas As Promising Therapeutic Targets and Biomarkers Formentioning

confidence: 99%

Section: Features and Functional Modules Of Lncrnas In Tumor Immune Rmentioning

confidence: 99%

Section: Expression Of Molecules In Tumor Cellsmentioning

confidence: 99%

Section: Expression Of Molecules In Tumor Cellsmentioning

confidence: 99%

Section: The Preclinical and Clinical Applications Of Lncrnas In Cancmentioning

confidence: 99%

See 3 more Smart Citations

Long Non-coding RNAs: Emerging Roles in the Immunosuppressive Tumor Microenvironment

Luo

Yang

et al. 2020

Front. Oncol.

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Significance of Selective Protein Degradation in the Development of Novel Targeted Drugs and Its Implications in Cancer Therapy

Yang

Wang

Feng

et al. 2020

Advanced Therapeutics

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The evolution of traditional chemotherapeutic drugs to targeted drugs has led to major changes in cancer treatment. However, it remains difficult to develop effective targeted drugs that can act against “undruggable” proteins, including some well‐known oncoproteins such as KRas. Moreover, mutations of target genes limit the use of targeted drugs. Although some strategies such as RNA interference and DNA editing have been adopted to solve these problems, their clinical use remains challenging. Therefore, new strategies are urgently needed to meet the dilemmas encountered in the use of targeted drugs. As protein degradation is a rapid and well‐regulated biological process in cells, targeting protein degradation by inducing cellular protein degradation machinery, regardless of the status of the target, is an attractive idea for developing novel targeted drugs. This review summarizes recent advances in targeted protein degradation, with a focus on the current reagents and strategies used for inducing selective degradation of target proteins to provide clues for the development of novel anticancer drugs and cancer therapies.

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LncRNA LINK‐A Remodels Tissue Inflammatory Microenvironments to Promote Obesity

Chen,

Wang

et al. 2023

Advanced Science

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High‐fat diet (HFD)‐induced obesity is a crucial risk factor for metabolic syndrome, mainly due to adipose tissue dysfunctions associated with it. However, the underlying mechanism remains unclear. This study has used genetic screening to identify an obesity‐associated human lncRNA LINK‐A as a critical molecule bridging the metabolic microenvironment and energy expenditure in vivo by establishing the HFD‐induced obesity knock‐in (KI) mouse model. Mechanistically, HFD LINK‐A KI mice induce the infiltration of inflammatory factors, including IL‐1β and CXCL16, through the LINK‐A/HB‐EGF/HIF1α feedback loop axis in a self‐amplified manner, thereby promoting the adipose tissue microenvironment remodeling and adaptive thermogenesis disorder, ultimately leading to obesity and insulin resistance. Notably, LINK‐A expression is positively correlated with inflammatory factor expression in individuals who are overweight. Of note, targeting LINK‐A via nucleic acid drug antisense oligonucleotides (ASO) attenuate HFD‐induced obesity and metabolic syndrome, pointing out LINK‐A as a valuable and effective therapeutic target for treating HFD‐induced obesity. Briefly, the results reveale the roles of lncRNAs (such as LINK‐A) in remodeling tissue inflammatory microenvironments to promote HFD‐induced obesity.

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Oncogenic lncRNA downregulates cancer cell antigen presentation and intrinsic tumor suppression

Cited by 282 publications

References 60 publications

Long Non-coding RNAs: Emerging Roles in the Immunosuppressive Tumor Microenvironment

Long Non-coding RNAs: Emerging Roles in the Immunosuppressive Tumor Microenvironment

Significance of Selective Protein Degradation in the Development of Novel Targeted Drugs and Its Implications in Cancer Therapy

LncRNA LINK‐A Remodels Tissue Inflammatory Microenvironments to Promote Obesity

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