Caveolin‑1 facilitated KCNA5 expression, promoting breast cancer viability

Qu, Chao; Sun, Jia; Liu, Ying; Wang, Xiaobo; Wang, Lifen; Han, Chao; Chen, Qian; Guan, Tianhui; Li, Hongyan; Zhang, Yejun; Wang, Yang; Liu, Jia; Zou, Wei; Liu, Jing

doi:10.3892/ol.2018.9261

Cited by 7 publications

(7 citation statements)

References 50 publications

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“…For example, KCNK5 , KCNK9 , and KCNK12 were highly expressed, and KCNK6 and KCNK15 were down-regulated in breast cancer [60]. The dysregulation of KCNA5 has also identified in colorectal cancer [51] and breast cancer [61]. Similar to our results, increased KCNN4 expression was identified with aggressive features of lung carcinoma [62].…”

Section: Discussionsupporting

confidence: 83%

Expression of potassium channel genes predicts clinical outcome in lung cancer

Kim

Lee

et al. 2019

Korean J Physiol Pharmacol

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Lung cancer is the most common cause of cancer deaths worldwide and several molecular signatures have been developed to predict survival in lung cancer. Increasing evidence suggests that proliferation and migration to promote tumor growth are associated with dysregulated ion channel expression. In this study, by analyzing high-throughput gene expression data, we identify the differentially expressed K+ channel genes in lung cancer. In total, we prioritize ten dysregulated K+ channel genes (5 up-regulated and 5 down-regulated genes, which were designated as K-10) in lung tumor tissue compared with normal tissue. A risk scoring system combined with the K-10 signature accurately predicts clinical outcome in lung cancer, which is independent of standard clinical and pathological prognostic factors including patient age, lymph node involvement, tumor size, and tumor grade. We further indicate that the K-10 potentially predicts clinical outcome in breast and colon cancers. Molecular signature discovered through K+ gene expression profiling may serve as a novel biomarker to assess the risk in lung cancer.

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Section: Discussionsupporting

confidence: 83%

Expression of potassium channel genes predicts clinical outcome in lung cancer

Kim

Lee

et al. 2019

Korean J Physiol Pharmacol

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“…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 ]. TAGLN is a potentially useful diagnostic marker differentially expressed in TNBC and a potential target for treatment strategies [ 83 ].…”

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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“…Potassium voltage-gated channel subfamily A member 5 (KCNA5) has been found to be associated with cell proliferation and apoptosis in various cell types (Ryland et al, 2015;Qu et al, 2018). Recently, KCNA5 has been shown to participate in miR-3940-5p-mediated granulosa cell proliferation in PCOS (Gao et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

miR-3188 Regulates proliferation and apoptosis of granulosa cells by targeting KCNA5 in the polycystic ovary syndrome

et al. 2021

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Abnormal proliferation of granulosa cells is implicated in ovarian dysfunction and dysregulated folliculogenesis in the polycystic ovary syndrome (PCOS). Aberrant microRNA (miRNA) expression might contribute to disordered folliculogenesis and granulosa cell proliferation in PCOS. This study aimed to investigate the roles of miR-3188 in ovarian dysfunction, as well as the mechanism involved in granulosa cell proliferation in PCOS. Firstly, peripheral blood samples were isolated from PCOS patients and healthy controls, and qRT-PCR analysis demonstrated a dramatic increase in miR-3188 in PCOS patients when compared to the healthy controls. Secondly, miR-3188 overexpression increased cell viability of the granulosa-like tumor cell line (KGN). However, cell viability of KGN was repressed by interference with miR-3188. MiR-3188 promoted cell cycle of KGN through increasing cyclinD1 and decreasing p21 levels. Moreover, cell apoptosis was suppressed by miR-3188 in KGN, indicated by enhanced Bcl-2, and reduced Bax and cleaved caspase-3 levels, whereas knockdown of miR-3188 resulted in opposite effects. Lastly, potassium voltage-gated channel subfamily A member 5 (KCNA5) was verified as a target of miR-3188. KCNA5 expression was decreased and displayed negative correlation with miR-3188 levels in PCOS patients. Overexpression of KCNA5 attenuated the promotive effects of miR-3188 on cell viability and cell cycle in KGN. In conclusion, miR-3188, a key miRNA enhanced in PCOS, promoted granulosa cell proliferation through down-regulation of KCNA5, providing a new therapeutic target for PCOS.

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Caveolin‑1 facilitated KCNA5 expression, promoting breast cancer viability

Cited by 7 publications

References 50 publications

Expression of potassium channel genes predicts clinical outcome in lung cancer

Expression of potassium channel genes predicts clinical outcome in lung cancer

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

miR-3188 Regulates proliferation and apoptosis of granulosa cells by targeting KCNA5 in the polycystic ovary syndrome

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