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

Abstract

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.

RNA sequencing of long-term label-retaining colon cancer stem cells identifies novel regulators of quiescence

“…Interestingly, we find that many of the genes that make up the molecular signature of these quiescent revSCs are also enriched in qCSCs and have been found to regulate therapy resistance in various types of cancer. These common genes include CLU ( Koltai, 2014 ); CTSD ( Mahajan et al, 2020 ; Oliveira et al, 2015 ); CDKN1A ( Koster et al, 2010 ; Liu et al., 2013 ; Maiuthed et al, 2018 ; Morris-Hanon et al, 2017 ; Xia et al, 2011 ); EMP1 ( Ariës et al, 2014 ; Jain et al, 2005 ); MUC3 ( Lesuffleur et al, 1993 ); LAMC2 ( Huang et al, 2017 ); KRT19 ( Asfaha et al, 2015 ); LGALS3 ( Wang et al, 2019 ); F3 , ITM2B , and ITGB4 ( Folgiero et al, 2008 ; Stewart and O'Connor, 2015 ); CDH17 ( Atukorala and Mathivanan, 2018 ; Qiu et al, 2013 ); and GSN ( Chung et al., 2015 ; Ilmer et al, 2016 ) ( Figures 3 D, 3E, and S1 and Data S1 ). Considering that colon cancer is a heterogeneous tumor that recapitulates the cellular hierarchy of the intestine, these data suggest that the qCSCs identified here may be the tumor equivalent of revSCs.…”

Viability and Morphology of Human Dental Pulp Stem Cells in the Presence of Citrus Pectin

“…In this study, the decrease in the viability of hDPSCs may be explained by the interaction of pectin and galectin-3. Galectin-3 as a sub-group of carbohydrate binding galectin family is responsible for cell adhesion, proliferation, survival, tumor cell proliferation and metastasis [25]. It is also expressed in MSCs and can affect immunomodulatory properties of these cells [56].…”

“…Their chemoresistance is mainly because of high expression of multi drug resistance proteins such as ABC transporters [21][22][23]. In addition, increased expression of galectin-3, is related to cancer development and metastasis, in tumor cells [24,25] and cancer stem cells are shown in the studies [26]. There are some therapeutic strategies for inhibition of cancer stem cells including monoclonal antibodies and micro RNA technologies [23] and different types of pectin molecules may help the inhibition of cellular activity.…”

Identification of CDKL3 as a critical regulator in development of glioma through regulating RRM2 and the JNK signaling pathway

“…The construction of the microarray and the following immunohistochemistry were carried out as described previously by Shanghai Biochip Company 39 . Glioma and normal tissue sections from glioma patients were deparaffinized, repaired with citrate antigen, blocked, and treated with 5% goat serum for 15 minutes at room temperature.…”