Galectin‑3 rs4652 A&gt;C polymorphism is associated with the risk of gastric carcinoma and P‑glycoprotein expression level

Shi, Yi; Lin, Xiandong; Chen, Gang; Yan, Jing; Ying, Mingang; Zheng, Xiongwei

doi:10.3892/ol.2017.7258

Cited by 8 publications

(12 citation statements)

References 32 publications

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“…Though lacking sufficient tissue for enough DNA to validate the relationship between the two SNPs and clinical and pathologic characteristics of the patients in our cohort, we first determined the positive impact of the C allele of rs4652 combined with the A allele of rs4644 on resistance to ionizing irradiation and chemotherapeutic drug in glioblastoma. As reported previously, amino acids Ala62-Tyr63 of the LGALS3 harbor the cleavage site for matrix metalloproteinases (MMP) and rs4644 rendering residue 64 of LGALS3 changing from histidine to proline may alter the pattern of MMPs cleavage, which may result in elevated LGALS3 level (46,47). However, different from the enhanced phenotypes of treatment resistance, the difference of cell proliferation abilities between þ191 A -þ292 C and þ191 C -þ292 A groups was not observed in T98G and U251 cells, which indicated diverse signaling pathways underlying LGALS3 in glioblastoma progression.…”

Section: Discussionmentioning

confidence: 86%

LGALS3 Promotes Treatment Resistance in Glioblastoma and Is Associated with Tumor Risk and Prognosis

Wang

Song

Huang

et al. 2019

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: LGALS3 promotes tumor progression in diverse cancers. However, the involvement of LGALS3 in glioblastoma has not yet been broadly illuminated. Methods: Microarray was performed to detect the gene expression profiles of radioresistance in T98G cells and identified a universally upregulated gene, LGALS3. The impact of LGALS3 on the survival of glioblastoma cells facing ionizing irradiation or temozolomide was investigated by the Cell Counting Kit-8 (CCK-8). A total of 120 glioblastoma cases were collected to analyze the relationship between LGALS3 expression and patient prognosis. Another 961 patients with glioma and 1,351 healthy controls were recruited to study the association of SNPs across the LGALS3 gene with glioblastoma susceptibility. The functional SNP sites were also studied in cellular experiments. Results: An effective protection of LGALS3 from ionizing irradiation or temozolomide-induced cell death in T98G and U251 cells was found. In addition, high expression of LGALS3 could work as an independent risk factor for survival of patients with glioblastoma. Two SNP sites (rs4644 and rs4652) across the LGALS3 gene were associated with increased risk for glioblastoma, and the C allele of rs4652 and the A allele of rs4644 could enhance glioblastoma resistance to radio-chemotherapy, but not cell proliferation. Conclusions: Our results suggest that LGALS3 is an important biomarker influencing glioblastoma risk and prognosis and a potential target for treating the malignancy, especially ones with resistance against the standard therapy. Impact: LGALS3 promotes glioblastoma cells' resistance to ionizing irradiation and temozolomide and predicts poor prognosis. Targeting LGALS3 may limit the therapeutic resistance in glioblastoma and increase patient survival.

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Section: Discussionmentioning

confidence: 86%

LGALS3 Promotes Treatment Resistance in Glioblastoma and Is Associated with Tumor Risk and Prognosis

Wang

Song

Huang

et al. 2019

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…It is associated with rheumatoid arthritis (Hu et al. 2011), risk for gastric carcinoma (Shi et al. 2011), differential LGALS3 gene expression, and differential Galectin-3 circulation levels in the blood (de Boer et al.…”

Section: Resultsmentioning

confidence: 99%

“…rs4652 has been implicated in diseases such as rheumatoid arthritis and gastric carcinoma (Hu et al. 2011; Shi et al. 2011).…”

Section: Discussionmentioning

confidence: 99%

The Impact of Natural Selection on the Evolution and Function of Placentally Expressed Galectins

Ely

Moon

Sliwoski

et al. 2019

Genome Biology and Evolution

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Immunity genes have repeatedly experienced natural selection during mammalian evolution. Galectins are carbohydrate-binding proteins that regulate diverse immune responses, including maternal–fetal immune tolerance in placental pregnancy. Seven human galectins, four conserved across vertebrates and three specific to primates, are involved in placental development. To comprehensively study the molecular evolution of these galectins, both across mammals and within humans, we conducted a series of between- and within-species evolutionary analyses. By examining patterns of sequence evolution between species, we found that primate-specific galectins showed uniformly high substitution rates, whereas two of the four other galectins experienced accelerated evolution in primates. By examining human population genomic variation, we found that galectin genes and variants, including variants previously linked to immune diseases, showed signatures of recent positive selection in specific human populations. By examining one nonsynonymous variant in Galectin-8 previously associated with autoimmune diseases, we further discovered that it is tightly linked to three other nonsynonymous variants; surprisingly, the global frequency of this four-variant haplotype is ∼50%. To begin understanding the impact of this major haplotype on Galectin-8 protein structure, we modeled its 3D protein structure and found that it differed substantially from the reference protein structure. These results suggest that placentally expressed galectins experienced both ancient and more recent selection in a lineage- and population-specific manner. Furthermore, our discovery that the major Galectin-8 haplotype is structurally distinct from and more commonly found than the reference haplotype illustrates the significance of understanding the evolutionary processes that sculpted variants associated with human genetic disease.

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“…Are there certain diseases associated with the SNP? [ 86 ]. Previous scientific work in this area unfortunately does not clarify this point [ 87 , 88 ].…”

Section: Non-classical Secretion Of Galectinsmentioning

confidence: 99%

Galectins in Intra- and Extracellular Vesicles

Bänfer

Jacob

2020

Biomolecules

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Carbohydrate-binding galectins are expressed in various tissues of multicellular organisms. They are involved in autophagy, cell migration, immune response, inflammation, intracellular transport, and signaling. In recent years, novel roles of galectin-interaction with membrane components have been characterized, which lead to the formation of vesicles with diverse functions. These vesicles are part of intracellular transport pathways, belong to the cellular degradation machinery, or can be released for cell-to-cell communication. Several characteristics of galectins in the lumen or at the membrane of newly formed vesicular structures are discussed in this review and illustrate the need to fully elucidate their contributions at the molecular and structural level.

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Galectin‑3 rs4652 A>C polymorphism is associated with the risk of gastric carcinoma and P‑glycoprotein expression level

Cited by 8 publications

References 32 publications

LGALS3 Promotes Treatment Resistance in Glioblastoma and Is Associated with Tumor Risk and Prognosis

LGALS3 Promotes Treatment Resistance in Glioblastoma and Is Associated with Tumor Risk and Prognosis

The Impact of Natural Selection on the Evolution and Function of Placentally Expressed Galectins

Galectins in Intra- and Extracellular Vesicles

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