Cancer Genetics
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2023
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IF 1.9
Shuoyi Zhang,Ming Zhong,Hongbo Zhu,Qinghua You,Hao Yuan,Yongping Li
ABSTRACT We investigated the effect of stem cell marker dopamine receptor D2 (DRD2) on the proliferation of hormone-receptor-negative breast cancer cells. High-throughput DNA methylation sequencing on an 850K chip was used to pre-screen breast cancer tissues with significant methylation differences. The expression of DRD2 in breast cancer and normal breast tissues, and clinical risk factors, were detected by pyrophosphoric acid validation and immunohistochemistry. In vitro and in vivo experiments verified the possible molecular signaling pathways. DRD2 promoter region was hypomethylated in hormone-receptor-negative breast cancer or with high-risk factors compared to the normal tissues. The proliferation of breast cancer cells was enhanced after DRD2 was upregulated and decreased after DRD2 was downregulated. In vivo experiments found that tumor growth and the expression of antigen KI-67 (Ki67) and the cluster of differentiation 31 (CD31) were improved by the overexpression of DRD2 and inhibited by the down expression of DRD2. In vivo and in vitro experiments demonstrated the phosphorylation of filamin A and extracellular signal-regulated kinase (FLNA-ERK) was influenced by the expression of DRD2, suggesting DRD2 plays a role in the FLNA-ERK signaling pathway. Methylation inhibitors (5-aza-2-deoxycytidine, 5-azadc) partially reversed the inhibitory effect of DRD2 down expression on cell proliferation, migration, and tumor growth in animal models, indicating that inhibition of DRD2 methylation promotes cancer development. This study demonstrated the DRD2 promoter region is hypomethylated in hormone-receptor-negative breast cancer or with high-risk factors. The methylation status of the DRD2 promoter and FLNA-ERK signaling pathway and the DRD2 expression in breast cancer treatment need to be considered.
研究领域:
肿瘤学
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分子生物学
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癌症遗传学
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产品关联
DOI
PubMed
高影响因子
CANCER GENE THERAPY
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2021
·Vol. 29
·期 1
·101-121
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IF 5.987
Pan Jiongwei,Huang Gang,Yin Zhangyong,Cai Xiaoping,Gong Enhui,Li Yuling,Xu Cunlai,Ye Zaiting,Cao Zhuo,Cheng Wei
Significantly high-expressed circFLNA has been found in various cancer cell lines, but not in lung cancer. Therefore, this study aimed to explore the role of circFLNA in the progression of lung cancer. The target gene of circFLNA was determined by bioinformatics and luciferase reporter assay. Viability, proliferation, migration, and invasion of the transfected cells were detected by CCK-8, colony formation, wound-healing, and transwell assays, respectively. A mouse subcutaneous xenotransplanted tumor model was established, and the expressions of circFLNA, miR-486-3p, XRCC1, CYP1A1, and related genes in the cancer cells and tissues were detected by RT-qPCR, Western blot, or immunohistochemistry. The current study found that miR-486-3p was low-expressed in lung cancer. MiR-486-3p, which has been found to target XRCC1 and CYP1A1, was regulated by circFLNA. CircFLNA was located in the cytoplasm and had a high expression in lung cancer cells. Cancer cell viability, proliferation, migration, and invasion were promoted by overexpressed circFLNA, XRCC1, and CYP1A1 but inhibited by miR-486-3p mimic and circFLNA knockdown. The weight of the xenotransplanted tumor was increased by circFLNA overexpression yet reduced by miR-486-3p mimic. Furthermore, miR-486-3p mimic reversed the effect of circFLNA overexpression on promoting lung cancer cells and tumors and regulating the expressions of miR-486-3p, XRCC1, CYP1A1, and metastasis/apoptosis/proliferation-related factors. However, overexpressed XRCC1 and CYP1A1 reversed the inhibitory effect of miR-486-3p mimic on cancer cells and tumors. In conclusion, circFLNA acted as a sponge of miR-486-3p to promote the proliferation, migration, and invasion of lung cancer cells in vitro and in vivo by regulating XRCC1 and CYP1A1.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
PROTEOMICS
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2024
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IF 3.4
Chao He,Xiuyuan Chen,Ying Chen,Jianying Sun,Manting Qi,Sonia Rocha,Mu Wang
Prostate cancer (PCa) is one of the leading causes of cancer morbidity and mortality in men. Metastasis is the main cause of PCa-associated death. Recent evidence indicated a significant reduction in PCa mortality associated with higher ω-3 polyunsaturated fatty acids (PUFAs) consumption. However, the underlying mechanisms remained elusive. In this study, we applied global acetylome profiling to study the effect of fatty acids treatment. Results indicated that oleic acid (OA, monounsaturated fatty acid, MUFA, 100 µM) elevates while EPA (eicosapentaenoic acid, 100 µM) reduces the acetyl-CoA level, which alters the global acetylome. After treatment, two crucial cell motility regulators, PFN1 and FLNA, were found with altered acetylation levels. OA increased the acetylation of PFN1 and FLNA, whereas EPA decreased PFN1 acetylation level. Furthermore, OA promotes while EPA inhibits PCa migration and invasion. Immunofluorescence assay indicated that EPA impedes the formation of lamellipodia or filopodia through reduced localization of PFN1 and FLNA to the leading edge of cells. Therefore, perturbed acetylome may be one critical step in fatty acid-affected cancer cell motility. This study provides some new insights into the response of ω-3 PUFAs treatment and a better understanding of cancer cell migration and invasion modulation.
研究领域:
肿瘤学
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生物化学
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细胞生物学
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营养学
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产品关联
DOI
PubMed
高影响因子
REPRODUCTIVE TOXICOLOGY
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2021
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IF 3.143
Jiadong Chen,Lian Kang,Junke Wang,Yuhao Wu,Lindong Han,Xiangqin Zheng,Yuexin Wei,Tianxin Zhao,Lianju Shen,Chunlan Long,Guanghui Wei,Shengde Wu
Di-(2-ethylhexyl) phthalate (DEHP) is an environmental endocrine disruptor that accumulates in organisms in various ways and induces male reproductive system disorders. In this study, we established a testicular injury model by gavage with different concentrations of DEHP. The testes were then collected for RNA sequencing (RNA-seq), and the results were analyzed by bioinformatics and verified by experiments. Our research results show that different concentrations of DEHP interfere with testicular development differently. Weighted gene coexpression network analysis (WGCNA) generated sixteen modules and identified the turquoise module as key. Then, estrogen receptor 1 (ESR1), filamin A (Flna) and Furin were identified as hub genes. qPCR and immunohistochemistry results revealed that all three hub genes were upregulated. We detected the locations of these genes by immunohistochemistry. ESR1 was mainly located in Leydig cells; Flna immunostaining is observed in the Leydig and some germ cells and Furin staining was seen in almost all types of testicular cells. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed enrichment mainly in MAPK signaling pathways, p53 signaling pathways, HIF-1 signaling pathways, protein processing in the endoplasmic reticulum, apoptosis, the cell cycle, RNA degradation, etc. This is the first study using WGCNA to investigate the mechanism of DEHP-induced injury in the prepubertal testis, providing new research angles to further understand the mechanism of DEHP-induced injury in the prepubertal testis.
研究领域:
毒理学
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生殖生物学
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分子生物学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
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