Extracellular Acidosis Promotes Metastatic Potency via Decrease of the BMAL1 Circadian Clock Gene in Breast Cancer

Kwon, Yong Jin; Seo, Eun Bi; Kwon, Sun-Ho; Lee, Song Hee; Kim, Seul Ki; Kim, Kyungjin; Park, Sae Gwang; Park, In-Cheol; Park, Jong-Wan; Ye, Sang Kyu

doi:10.3390/cells9040989

Cited by 21 publications

(13 citation statements)

References 58 publications

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“…Additionally, altered circadian rhythms have been reported to be correlated with the prognosis of breast cancer [61].The exist circadian rhythm and the core circadian gene Bmal1, persist in malignancy breast cancer cells [61]. Tumor hypoxia-induced acidosis decreases the transcription activation and protein stability of BMAL1 to promote breast cancer metastasis in vitro [62]. Moreover, members of PER subfamily, including PER-1, PER-2, and PER-3, have been reported to be lowly expressed and play significant role in NSCLC patients [63].…”

Section: Disruption Of the Circadian Clock Contributes To Cancermentioning

confidence: 99%

Circadian clock: a regulator of the immunity in cancer

et al. 2021

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The circadian clock is an endogenous timekeeper system that controls and optimizes biological processes, which are consistent with a master circadian clock and peripheral clocks and are controlled by various genes. Notably, the disruption of circadian clock genes has been identified to affect a wide range of ailments, including cancers. The cancer-immunity cycle is composed of seven major steps, namely cancer cell antigen release and presentation, priming and activation of effector immunity cells, trafficking, and infiltration of immunity to tumors, and elimination of cancer cells. Existing evidence indicates that the circadian clock functions as a gate that govern many aspects of the cancer-immunity cycle. In this review, we highlight the importance of the circadian clock during tumorigenesis, and discuss the potential role of the circadian clock in the cancer-immunity cycle. A comprehensive understanding of the regulatory function of the circadian clock in the cancer-immunity cycle holds promise in developing new strategies for the treatment of cancer.

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Section: Disruption Of the Circadian Clock Contributes To Cancermentioning

confidence: 99%

Circadian clock: a regulator of the immunity in cancer

et al. 2021

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“…Membranes were blocked in 5% skim-milk for 1 h and incubated with primary antibodies overnight at 4 °C. Membranes were incubated with a horseradish peroxidase (HRP)-conjugated secondary antibodies for 1 h, and then visually evaluated by using the ECL detection kit (Biomax Co., Ltd, Seoul, Korea) 27 .…”

Section: Characterizationmentioning

confidence: 99%

Insulin smart drug delivery nanoparticles of aminophenylboronic acid–POSS molecule at neutral pH

Kim

Kwon

Cho

et al. 2021

Sci Rep

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Self-regulated “smart” insulin administration system that mimic pancreatic endocrine function would be highly desirable for diabetes management. Here, a glucose-responsive continuous insulin delivery system is developed, where novel polyhedral oligosilsesquioxane (POSS) modified with 3‐aminophenylboronic acid (APBA) were used to encapsulate insulin (insulin entrapment efficiency: 73.2%) to prepare a fast response, high stability, good distribution, and excellent biocompatible system. Due to the strong hydrophobicity of POSS, the POSS moiety is located at the core in aqueous solution and combines with the boronic group of APBA and the diol generated in PEG-insulin to form a nanomicelle structure, that is, nanoparticles naturally. Micelles self‐assembled from these molecules possess glucose‐responsiveness at varying glucose concentrations. The interaction of the PBA and diol containing insulin via boronate ester bond and its interchange with glucose was investigated by FT-IR, 1H NMR and XPS. Furthermore, the successful glucose-triggered release of insulin from the POSS-APBA micelles was investigated at neutral pH. A linear graph was plotted with the measured released insulin vs glucose concentrations, with a linear correlation coefficient (R2) value close to 1. Circular dichroism (CD) spectroscopy analysis was performed to measure insulin activity by comparing secondary structures of insulin, PEG-Insulin, and POSS-APBA@insulin. When confirming intracellular apoptosis signaling, cleaved caspase 3 and caspase 9 were not increased by 640 μg/ml POSS-APBA and POSS-APBA@insulin in HeLa, HDF and HUVE cells. Application in the biomedical field for controlled delivery of insulin appear to be promising.

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“…In addition, abnormal expression levels of circadian clock genes are closely related to tumor development. Studies have found that mutations in BMAL1, CRY1, and CRY2 are often associated with a higher risk and recurrence of acute myeloid leukemia and endometrial, ovarian, colorectal, and breast cancers ( Hasakova et al, 2018 ; Burgermeister et al, 2019 ; Kwon et al, 2020 ). Per 1 , Per 2 , and Per 3 are frequently expressed in human breast and colorectal cancers, non-small-cell lung cancer (NSCLC), hepatocellular and cervical squamous cell carcinomas, and glioma ( Yeh et al, 2005 ; Mostafaie et al, 2009 ; Lin et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis of Differentially Expressed Rhythm Genes in Liver Hepatocellular Carcinoma

Liu

Gao

et al. 2021

Front. Genet.

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Liver Hepatocellular Carcinoma (LIHC), a malignant tumor with high incidence and mortality, is one of the most common cancers in the world. Multiple studies have found that the aberrant expression of rhythm genes is closely related to the occurrence of LIHC. This study aimed to use bioinformatics analysis to identify differentially expressed rhythm genes (DERGs) in LIHC. A total of 563 DERGs were found in LIHC, including 265 downregulated genes and 298 upregulated genes. KEGG pathway enrichment and GO analyses showed that DERGs were significantly enriched in rhythmic and metabolic processes. Survival analysis revealed that high expression levels of CNK1D, CSNK1E, and NPAS2 were significantly associated with the low survival rate in LIHC patients. Through cell experiment verification, the mRNA expression levels of CSNK1D, CSNK1E, and NPAS2 were found to be strongly upregulated, which was consistent with the bioinformatics analysis of LIHC patient samples. A total of 23 nodes and 135 edges were involved in the protein–protein interaction network of CSNK1D, CSNK1E, and NPAS2 genes. Clinical correlation analyses revealed that CSNK1D, CSNK1E, and NPAS2 expression levels were high-risk factors and independently connected with the overall survival rate in LIHC patients. In conclusion, the identification of these DERGs contributes to the exploration of the molecular mechanisms of LIHC occurrence and development and may be used as diagnostic and prognostic biomarkers and molecular targets for chronotherapy in LIHC patients in the future.

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Extracellular Acidosis Promotes Metastatic Potency via Decrease of the BMAL1 Circadian Clock Gene in Breast Cancer

Cited by 21 publications

References 58 publications

Circadian clock: a regulator of the immunity in cancer

Circadian clock: a regulator of the immunity in cancer

Insulin smart drug delivery nanoparticles of aminophenylboronic acid–POSS molecule at neutral pH

Bioinformatics Analysis of Differentially Expressed Rhythm Genes in Liver Hepatocellular Carcinoma

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