The microRNA-152/human leukocyte antigen-G axis affects proliferation and immune escape of non-small cell lung cancer cells

Fu, Jun; Murata, Jun; Wang, Chun

doi:10.1177/0300060520970758

Cited by 8 publications

(10 citation statements)

References 35 publications

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“…This finding suggests the possibility of considering this molecule as a potential target for therapeutic approaches. Downregulating HLA-G expression with miRNAs (as has been done in other clinical settings) ( 53 – 55 ) or blocking (with monoclonal antibodies) its interaction with cognate receptors (in a way similar to PD-1/PD-L1 current immunotherapies) ( 56 – 58 ), will make tumors visible to immunocompetent cells, eliciting an active immune response.…”

Section: Discussionmentioning

confidence: 99%

HLA-G 3’UTR Polymorphisms Are Linked to Susceptibility and Survival in Spanish Gastric Adenocarcinoma Patients

et al. 2021

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HLA-G is a non-classical class I HLA molecule that induces tolerance by acting on receptors of both innate and adaptive immune cells. When overexpressed in tumors, limits surveillance by the immune system. The HLA-G gene shows several polymorphisms involved in mRNA and protein levels. We decided to study the implication of two polymorphisms (rs371194629; 14bp INS/DEL and rs1063320; +3142 C/G) in paired tissue samples (tumoral and non-tumoral) from 107 Spanish patients with gastric adenocarcinoma and 58 healthy control individuals, to assess the possible association of the HLA-G gene with gastric adenocarcinoma susceptibility, disease progression and survival. The presence of somatic mutations involving these polymorphisms was also analyzed. The frequency of the 14bp DEL allele was increased in patients (70.0%) compared to controls (57.0%, p=0.025). In addition, the haplotype formed by the combination of the 14bp DEL/+3142 C variants is also increased in patients (54.1% vs 44.4%, p=0.034, OR=1.74 CI95% 1.05-2.89). Kaplan-Meier analysis revealed that 14bp DEL/DEL patients showed lower 5-year life-expectancy than INS/DEL or INS/INS (p=0.041). Adjusting for TNM staging (Cox regression analysis) disclosed a significant difference in death risk (p=0.03) with an expected hazard 2.6 times higher. Finally, no somatic mutations were found when comparing these polymorphisms in tumoral vs non-tumoral tissues, which indicates that this is a preexisting condition in patients and not a de novo, tumor-restricted, event. In conclusion, the variants predominant in patients were those increasing HLA-G mRNA stability and HLA-G expression, clearly involving this molecule in gastric adenocarcinoma susceptibility, disease progression and survival and making it a potential target for immunotherapeutic approaches.

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Section: Discussionmentioning

confidence: 99%

HLA-G 3’UTR Polymorphisms Are Linked to Susceptibility and Survival in Spanish Gastric Adenocarcinoma Patients

et al. 2021

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“…Fu et al (103) found that HLA-G expression was directly regulated by miR-152, and also that an aberrant expression of miR-152 influenced tolerance to, in this case, NK cell cytolysis in vitro. The cell lysis rate increased significantly when overexpressing miR-152 in the target cells (A549 cells), because, as a consequence of this, they had less HLA-G to protect themselves from NK cellmediated lysis.…”

Section: Cancermentioning

confidence: 99%

“…Based on the two aforementioned works (102,103), it seems interesting to develop therapies with miRNAs aimed at reducing HLA-G expression in cancer, in order to restore the anti-tumor activity of cells restrained by this molecule.…”

Section: Cancermentioning

confidence: 99%

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HLA-G: Too Much or Too Little? Role in Cancer and Autoimmune Disease

et al. 2022

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HLA-G is a non-classical HLA class I molecule with immunomodulatory properties. It was initially described at the maternal-fetal interface, and it was later found that this molecule was constitutively expressed on certain immuneprivileged tissues, such as cornea, endothelial and erythroid precursors, and thymus. The immunosuppressive effect of HLA-G is exerted through the interaction with its cognate receptors, expressed on immunocompetent cells, like ILT2, expressed on NK, B, T cells and APCs; ILT4, on APCs; KIR, found on the surface of NK cells; and finally, the co-receptor CD8. Because of these immunomodulatory functions, HLA-G has been involved in several processes, amongst which organ transplantation, viral infections, cancer progression, and autoimmunity. HLA-G neo-expression on tumors has been recently described in several types of malignancies. In fact, tumor progression is tightly linked to the presence of the molecule, as it exerts its tolerogenic function, inhibiting the cells of the immune system and favoring tumor escape. Several polymorphisms in the 3’UTR region condition changes in HLA-G expression (14bp and +3142C/G, among others), which have been associated with both the development and outcome of patients with different tumor types. Also, in recent years, several studies have shown that HLA-G plays an important role in the control of autoimmune diseases. The ability of HLA-G to limit the progression of these diseases has been confirmed and, in fact, levels of the molecule and several of its polymorphisms have been associated with increased susceptibility to the development of autoimmune diseases, as well as increased disease severity. Thus, modulating HLA-G expression in target tissues of oncology patients or patients with autoimmune diseases may be potential therapeutic approaches to treat these pathological conditions.

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“…In the malignant environment where tumors occur, the expression of HLA-G in melanoma is first reported in 1998 (19), and then the abnormal expression of HLA-G is observed in a variety of malignant tumors, such as lung cancer (20)(21)(22)(23)(24)(25)(26)(27)(28), gastric cancer (29)(30)(31)(32)(33)(34)(35)(36)(37), ovarian cancer (OC) (38)(39)(40)(41)(42)(43)(44)(45)(46)(47), breast cancer (48)(49)(50)(51)(52)(53)(54), and hematopoietic tumor (55)(56)(57)(58). With the deepening of research, the expression of HLA-G in solid malignant tumors and its potential clinical relevance have attracted increasing attention (59).…”

Section: Introductionmentioning

confidence: 99%

HLA-G/sHLA-G and HLA-G-Bearing Extracellular Vesicles in Cancers: Potential Role as Biomarkers

Wang

Zhang

et al. 2021

Front. Immunol.

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As a non-classic major histocompatibility complex (MHC) class I molecule, human leukocyte antigen G (HLA-G) is expressed in fetal-maternal interface and immunoprivileged site only in healthy condition, and in pathological conditions such as cancer, it can be de novo expressed. It is now widely accepted that HLA-G is a key molecule in the process of immune escape of cancer cells, which is ubiquitously expressed in the tumor environment. This raises the possibility that it may play an adverse role in tumor immunity. The expression level of HLA-G has been demonstrated to be highly correlated with clinical parameters in many tumors, and its potential significance in the diagnosis and prognosis of cancer has been postulated. However, because HLA-G itself has up to seven different subtypes, and for some subtypes, detected antibodies are few or absent, it is hard to evaluate the actual expression of HLA-G in tumors. In the present work, we described (a) the structure and three main forms of HLA-G, (b) summarized the mechanism of HLA-G in the immune escape of tumor cells, (c) discussed the potential role of HLA-G as a tumor marker, and reviewed (d) the methods for detecting and quantifying HLA-G.

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The microRNA-152/human leukocyte antigen-G axis affects proliferation and immune escape of non-small cell lung cancer cells

Cited by 8 publications

References 35 publications

HLA-G 3’UTR Polymorphisms Are Linked to Susceptibility and Survival in Spanish Gastric Adenocarcinoma Patients

HLA-G 3’UTR Polymorphisms Are Linked to Susceptibility and Survival in Spanish Gastric Adenocarcinoma Patients

HLA-G: Too Much or Too Little? Role in Cancer and Autoimmune Disease

HLA-G/sHLA-G and HLA-G-Bearing Extracellular Vesicles in Cancers: Potential Role as Biomarkers

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