Molecular and functional characterization of galectin 9 mRNA isoforms in porcine and human cells and tissues

Spitzenberger, Folker; Graessler, Juergen; Schroeder, Hans-Egbert

doi:10.1016/s0300-9084(01)01335-9

Cited by 47 publications

(13 citation statements)

References 23 publications

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“…Notably, studies have suggested that posttranscriptional splicing may affect galectin-9 protein function. So far, 6 splice variants of galectin-9 have been identified based on exclusion of exons 5, 6 and 10[ 43 , 44 ]. Splice variants lacking exon 5 or/and 6 displayed altered length of the linker domain between the two carbohydrate recognition domains (CRDs), which influences the rotational freedom of both CRDs and increase gal-9 valency[ 45 , 46 ].Furthermore, other studies have reported splice variants that lack exon 10, such as gal-9Δ10, gal-9Δ5/10 and gal-9Δ5/6/10do not appear to be secreted[ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Reduced Expression of Galectin-9 Contributes to a Poor Outcome in Colon Cancer by Inhibiting NK Cell Chemotaxis Partially through the Rho/ROCK1 Signaling Pathway

Wang

Sun

et al. 2016

PLoS ONE

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Galectin-9 is a widely expressed protein that is involved in immune regulation and tumorpathogenesis and serves as a marker of a poor prognosis in various types of cancers. However, the clinical impact and the precise mechanism by which this protein contributes to colon tumor progression are unclear. In the present study, we detected the expression of galectin-9 and CD56 cells using immunohistochemistry. Spearman's rank correlation was used to clarify the association between galectin-9 expression and natural killer (NK) cell infiltration. The influence of galectin-9 on NK-92 cell migration was evaluated in vitro using transwell chemotaxis assays. The role of rh-galectin-9 in F-actin polarization in NK-92 cells was investigated using laser scanning confocal microscopy. We showed that galectin-9 was expressed in 101 (78.91%) colon tumor tissues and that was expressed at lower levels in these tissues than in para-tumor tissues. Low levels of galectin-9 expression were positively correlated with a poor histological grade and lymph node metastasis (P<0.05). A Kaplan-Meier method and Cox proportional hazards regression analysis showed that overall survival was longer in patients with high galectin-9 expression in an 8-year follow-up (P<0.05). Spearman's rank correlation indicated that there was a linear correlation between galectin-9 expression and CD56+ NK cell infiltration (R2 = 0.658; P<0.0001). Galectin-9 stimulated migration in human NK-92 cells by affecting F-actin polarization through the Rho/ROCK1 signaling pathway. These results suggest that galectin-9 expression potentially represents a novel mechanism for tumors to escape immune surveillance in colon tumors.

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Section: Discussionmentioning

confidence: 99%

Reduced Expression of Galectin-9 Contributes to a Poor Outcome in Colon Cancer by Inhibiting NK Cell Chemotaxis Partially through the Rho/ROCK1 Signaling Pathway

Wang

Sun

et al. 2016

PLoS ONE

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“…One ligand of TIM-3 is the C-type lectin galectin 9 (LGALS9) [9]. Galectin 9, encoded by the gene LGALS9 , is physiologically expressed in multiple cell types, especially in cells of lymphatic organs and in monocytes, but also in different tissue endothelial cells, small intestine, and in target cells for different viruses such as the hepatitis C virus [10–15]. Additionally, LGALS9 is expressed by tumor cells which can have diverse effects on different immune cells in the tumor microenvironment (reviewed in [16]).…”

Section: Introductionmentioning

confidence: 99%

Molecular and immune correlates of TIM-3 (HAVCR2) and galectin 9 (LGALS9) mRNA expression and DNA methylation in melanoma

et al. 2019

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BackgroundThe T cell immunoglobulin and mucin-domain containing-3 receptor TIM-3 (also known as hepatitis A virus cellular receptor 2, encoded by HAVCR2) and its ligand galectin 9 (LGALS9) are promising targets for immune checkpoint inhibition immunotherapies. However, little is known about epigenetic regulation of the encoding genes. This study aimed to investigate the association of TIM-3 and LGALS9 DNA methylation with gene expression, patients’ survival, as well as molecular and immune correlates in malignant melanoma.ResultsMethylation of all six TIM-3 CpGs correlated significantly with TIM-3 mRNA levels (P ≤ 0.05). A strong inverse correlation (Spearman’s ρ = − 0.49) was found in promoter regions, while a strong positive correlation (ρ = 0.63) was present in the gene body of TIM-3. High TIM-3 mRNA expression (hazard ratio (HR) = 0.88, 95% confidence interval (CI) [0.81–0.97], P = 0.007) was significantly associated with better overall survival. Seven of the eight LGALS9 CpG sites correlated significantly with LGALS9 mRNA levels (P ≤ 0.003). Methylation at five CpG sites showed a strong inverse correlation (Spearman’s ρ = − 0.67) and at two sites a weak positive correlation (Spearman’s ρ = 0.15). High LGALS9 mRNA expression was significantly associated with increased overall survival (HR = 0.83, 95%CI [0.75–0.93], P = 0.001). In addition, we found significant correlations between TIM-3 and LGALS9 methylation and mRNA expression with immune cell infiltrates and significant differences among distinct immune cell subsets.ConclusionsOur study points toward an epigenetic regulation of TIM-3 and LGALS9 via DNA methylation and might provide an avenue for the development of a predictive biomarker for response to immune checkpoint blockade.

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“…galectin-1, -3, -4, -7, -8, and -9, mRNA expression could be detected (Figure 1A). Because extensive splicing has been reported for galectin-9 [23], [25], [26], we also determined the mRNA expression of the most common galectin-9 splice variants, i.e. galectin-9 full length (FL), galectin-9 with a deletion of exon 5 (Δ5), and galectin-9 with a deletion of exons 5 and 6 (Δ5/6).…”

Section: Resultsmentioning

confidence: 99%

Galectin Expression Profiling Identifies Galectin-1 and Galectin-9Δ5 as Prognostic Factors in Stage I/II Non-Small Cell Lung Cancer

et al. 2014

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Approximately 30–40% of the patients with early stage non-small cell lung cancer (NSCLC) will present with recurrent disease within two years of resection. Here, we performed extensive galectin expression profiling in a retrospective study using frozen and paraffin embedded tumor tissues from 87 stage I/II NSCLC patients. Our data show that galectin mRNA expression in NSCLC is confined to galectin-1, -3, -4, -7, -8, and -9. Next to stage, univariable Cox regression analysis identified galectin-1, galectin-9FL and galectin-9Δ5 as possible prognostic markers. Kaplan-Meier survival estimates revealed that overall survival was significantly shorter in patients that express galectin-1 above median levels, i.e., 23.0 (2.9–43.1) vs. 59.9 (47.7–72.1) months (p = 0.020) as well as in patients that express galectin-9Δ5 or galectin-9FL below the median, resp. 59.9 (41.9–75.9) vs. 32.8 (8.7–56.9) months (p = 0.014) or 23.2 (−0.4–46.8) vs. 58.9 (42.9–74.9) months (p = 0.042). All three galectins were also prognostic for disease free survival. Multivariable Cox regression analysis showed that for OS, the most significant prognostic model included stage, age, gal-1 and gal-9Δ5 while the model for DFS included stage, age and gal-9Δ5. In conclusion, the current study confirms the prognostic value of galectin-1 and identifies galectin-9Δ5 as novel potential prognostic markers in early stage NSCLC. These findings could help to identify early stage NSCLC patients that might benefit most from adjuvant chemotherapy.

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Molecular and functional characterization of galectin 9 mRNA isoforms in porcine and human cells and tissues

Cited by 47 publications

References 23 publications

Reduced Expression of Galectin-9 Contributes to a Poor Outcome in Colon Cancer by Inhibiting NK Cell Chemotaxis Partially through the Rho/ROCK1 Signaling Pathway

Reduced Expression of Galectin-9 Contributes to a Poor Outcome in Colon Cancer by Inhibiting NK Cell Chemotaxis Partially through the Rho/ROCK1 Signaling Pathway

Molecular and immune correlates of TIM-3 (HAVCR2) and galectin 9 (LGALS9) mRNA expression and DNA methylation in melanoma

Galectin Expression Profiling Identifies Galectin-1 and Galectin-9Δ5 as Prognostic Factors in Stage I/II Non-Small Cell Lung Cancer

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