&lt;p&gt;Long Non-Coding RNA A2M-AS1 Promotes Breast Cancer Progression by Sponging microRNA-146b to Upregulate MUC19&lt;/p&gt;

Liu, Yuncong; Zhang, Qi; Wu, Jing; Zhang, Hanqun; Li, Xin; Zheng, Zhaopeng; Luo, Moulun; Li, Libo; Xiang, Yang; Yang, Feiyue; Wu, Li Hui

doi:10.2147/ijgm.s278564

Cited by 18 publications

(11 citation statements)

References 31 publications

(37 reference statements)

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“…MUC19 reportedly modulates proliferation, invasion and metastatic potential of breast cancer [ 80 ]. MUC19 expression was notably observed to increase in TNBC and found to be targeted by miR-593 [ 81 ]. KCNB1 is a complex class of voltage-gated ion channels and its overexpression was reported as biomarker in breast cancer [ 82 ].…”

Section: Discussionmentioning

confidence: 99%

Synergistic anti-proliferative activity of JQ1 and GSK2801 in triple-negative breast cancer

Yellapu

Sardiu

et al. 2022

BMC Cancer

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Background Triple-negative breast cancer (TNBC) constitutes 10–20% of breast cancers and is challenging to treat due to a lack of effective targeted therapies. Previous studies in TNBC cell lines showed in vitro growth inhibition when JQ1 or GSK2801 were administered alone, and enhanced activity when co-administered. Given their respective mechanisms of actions, we hypothesized the combinatorial effect could be due to the target genes affected. Hence the target genes were characterized for their expression in the TNBC cell lines to prove the combinatorial effect of JQ1 and GSK2801. Methods RNASeq data sets of TNBC cell lines (MDA-MB-231, HCC-1806 and SUM-159) were analyzed to identify the differentially expressed genes in single and combined treatments. The topmost downregulated genes were characterized for their downregulated expression in the TNBC cell lines treated with JQ1 and GSK2801 under different dose concentrations and combinations. The optimal lethal doses were determined by cytotoxicity assays. The inhibitory activity of the drugs was further characterized by molecular modelling studies. Results Global expression profiling of TNBC cell lines using RNASeq revealed different expression patterns when JQ1 and GSK2801 were co-administered. Functional enrichment analyses identified several metabolic pathways (i.e., systemic lupus erythematosus, PI3K-Akt, TNF, JAK-STAT, IL-17, MAPK, Rap1 and signaling pathways) enriched with upregulated and downregulated genes when combined JQ1 and GSK2801 treatment was administered. RNASeq identified downregulation of PTPRC, MUC19, RNA5-8S5, KCNB1, RMRP, KISS1 and TAGLN (validated by RT-qPCR) and upregulation of GPR146, SCARA5, HIST2H4A, CDRT4, AQP3, MSH5-SAPCD1, SENP3-EIF4A1, CTAGE4 and RNASEK-C17orf49 when cells received both drugs. In addition to differential gene regulation, molecular modelling predicted binding of JQ1 and GSK2801 with PTPRC, MUC19, KCNB1, TAGLN and KISS1 proteins, adding another mechanism by which JQ1 and GSK2801 could elicit changes in metabolism and proliferation. Conclusion JQ1-GSK2801 synergistically inhibits proliferation and results in selective gene regulation. Besides suggesting that combinatorial use could be useful therapeutics for the treatment of TNBC, the findings provide a glimpse into potential mechanisms of action for this combination therapy approach.

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Section: Discussionmentioning

confidence: 99%

Synergistic anti-proliferative activity of JQ1 and GSK2801 in triple-negative breast cancer

Yellapu

Sardiu

et al. 2022

BMC Cancer

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“…A recent study reported that MUC19 was significantly upregulated in BC ( 38 ) and that patients with high MUC19 expression levels exhibited a worse prognosis ( 39 ). Liu et al ( 40 ) reported that MUC19 promotes cell proliferation, invasion and colony formation and inhibits apoptosis in BC. The present study also demonstrated that MUC19 was significantly upregulated in BC and promoted BC cell proliferation and invasion.…”

Section: Discussionmentioning

confidence: 99%

LOC102724163 promotes breast cancer cell proliferation and invasion by stimulating MUC19 expression

Jiang

Luo

2022

Oncol Lett

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Breast cancer (BC) is a malignant disease and the most commonly diagnosed cancer in women. Numerous studies have previously verified the important role of long non-coding RNAs in a number of biological processes in BC. In the present study, analysis of The Cancer Genome Atlas database and reverse transcription-quantitative PCR demonstrated that LOC102724163 expression levels were significantly upregulated in BC tissues compared to matched adjacent normal tissues and were associated with an unfavorable prognosis in patients with BC. Gain or loss of function assays indicated that overexpression of LOC102724163 significantly increased tumorgenicity in vivo and cell migration, proliferation and invasion in vitro . In the mechanistical aspect, LOC102724163 sponged microRNA (miR)-508-5p to elevate MUC19 expression. Additionally, rescue assays ascertained the function of the LOC102724163 /miR-508-5p/ MUC19 axis in the proliferation and invasion of BC cells. To the best of our knowledge, this is the first study to have demonstrated that LOC10272416 3 may act as a competing endogenous RNA to control MUC19 expression levels by competitively sponging miR-508-5p to modulate BC progression. Therefore, the present study has provided new insights into BC diagnosis and treatment.

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“…Three lncRNAs ( A2M-AS1 , C2orf27A , and ZNF667-AS1 ) were identified to be related to the hub FRGs. Among them, A2M-AS1 was reported to be involved in the invasion, migration, and progression of breast cancer ( Fang et al, 2020 ; Liu et al, 2020b ). In addition, A2M-AS1 was also reported to lessen cardiomyocyte injury caused by hypoxia/reoxygenation (H/R) by regulating IL1R2 ( Song et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

LncRNAs Target Ferroptosis-Related Genes and Impair Activation of CD4+ T Cell in Gastric Cancer

Yao

et al. 2021

Front. Cell Dev. Biol.

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Gastric cancer (GC) is a malignant disease of the digestive tract and a life-threatening disease worldwide. Ferroptosis, an iron-dependent cell death caused by lipid peroxidation, is reported to be highly correlated with gastric tumorigenesis and immune cell activity. However, the underlying relationship between ferroptosis and the tumor microenvironment in GC and potential intervention strategies have not been unveiled. In this study, we profiled the transcriptome and prognosis data of ferroptosis-related genes (FRGs) in GC samples of the TCGA-STAD dataset. The infiltrating immune cells in GC were estimated using the CIBERSORT and XCELL algorithms. We found that the high expression of the hub FRGs (MYB, PSAT1, TP53, and LONP1) was positively correlated with poor overall survival in GC patients. The results were validated in an external GC cohort (GSE62254). Further immune cell infiltration analysis revealed that CD4+ T cells were the major infiltrated cells in the tumor microenvironment of GC. Moreover, the hub FRGs were significantly positively correlated with activated CD4+ T cell infiltration, especially Th cells. The gene features in the high-FRG score group were enriched in cell division, DNA repair, protein folding, T cell receptor, Wnt and NIK/NF-kappaB signaling pathways, indicating that the hub FRGs may mediate CD4+ T cell activation by these pathways. In addition, an upstream transcriptional regulation network of the hub FRGs by lncRNAs was also developed. Three lncRNAs (A2M-AS1, C2orf27A, and ZNF667-AS1) were identified to be related to the expression of the hub FRGs. Collectively, these results showed that lncRNA A2M-AS1, C2orf27A, and ZNF667-AS1 may target the hub FRGs and impair CD4+ T cell activation, which finally leads to poor prognosis of GC. Effective interventions for the above lncRNAs and the hub FRGs can help promote CD4+ T cell activation in GC patients and improve the efficacy of immunotherapy. These findings provide a novel idea of GC immunotherapy and hold promise for future clinical application.

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<p>Long Non-Coding RNA A2M-AS1 Promotes Breast Cancer Progression by Sponging microRNA-146b to Upregulate MUC19</p>

Cited by 18 publications

References 31 publications

Synergistic anti-proliferative activity of JQ1 and GSK2801 in triple-negative breast cancer

Synergistic anti-proliferative activity of JQ1 and GSK2801 in triple-negative breast cancer

LOC102724163 promotes breast cancer cell proliferation and invasion by stimulating MUC19 expression

LncRNAs Target Ferroptosis-Related Genes and Impair Activation of CD4+ T Cell in Gastric Cancer

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