Pigment Cell & Melanoma Research
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2025
·Vol. 38
·期 4
·e70034
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IF 2.6
Man Cai,Liangyu Wang,Miao Sun,Meixi Liu,Yingchun Liu
Protein arginine methyltransferase 6 (PRMT6), a member of the PRMT family capable of self-arginine methylation, is down-regulated in melanoma, but the specific mechanism is still unclear. Our work demonstrated that PRMT6 overexpression significantly inhibited the ability of melanoma cells to proliferate, tumorigenicity, migration, and invasion, whereas PRMT6 knockdown rescued these malignant behaviors of melanoma cells. Mechanistically, we identified aldehyde dehydrogenase 1A1 (ALDH1A1) as a critical downstream target of PRMT6. PRMT6 knockdown up-regulated ALDH1A1 expression, exacerbating melanoma aggressiveness in vitro. Further investigations revealed that PRMT6 modulates ALDH1A1 expression by catalyzing asymmetric dimethylation of histone H3 at arginine 2 (H3R2me2a) and antagonizing the enrichment of histone H3 lysine 4 trimethylation (H3K4me3) at the ALDH1A1 promoter. In addition, dual-luciferase experiments showed that the transcription factor KLF4 may bind to the −1800 ~ +45 sequence of PRMT6, thereby negatively regulating PRMT6 expression in melanoma. Our findings underscore the tumor-suppressive role of PRMT6 in melanoma pathogenesis, highlighting its potential as a novel therapeutic target, particularly for metastatic melanoma.
研究领域:
癌症生物学
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分子生物学
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表观遗传学
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生物化学
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细胞生物学
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DOI
PubMed
高影响因子
Frontiers in Cell and Developmental Biology
·
2020
·
IF 5.186
Jiang Ying,Song Hanbing,Jiang Ling,Qiao Yu,Yang Dan,Wang Donghua,Li Ji
Background: Silybin was known to exert inhibition in prostate cancer, but the underlying mechanism remained largely unknown. This study was designed to find out the potential target of Silybin on prostate cancer and explore the relative mechanisms.Methods: Firstly, we screened the possible targets of Silybin through the PubChem database and Subpathway – GM. Then DU145 cells were transferred to investigate the correction about related targets, magnetic bead sorting and flow cytometry were used to sort and identify the cells. Proliferation, migration and invasion ability of DU145 cells were detected by MTT assay, Transwell assay, plate clonality and sphere formation assay. BALB/c nude mice were constructed models with implanted sarcoma and measured the tumor volume every 5 days as wells tumor weight. The levels of proteins were detected by Western blot and immunocytochemistry. RT-PCR was selected to test the expression of protein’s mRNA.Results: It was screened out the ALDH1A1 was highly correlated with subpathways of the Silybin risk metabolic pathway. And ALDH1A1 expression was positively correlated RARα with Ets1 by interfering with the ALDH1A1 gene. Importantly, ALDH1A1(+) cells showed proliferation, migration and invasion ability. In addition, it showed that Silybin exerted the inhibition on prostate cells by suppressed the proliferation, migration and invasion ability of cells in vitro experiment. Silybin also reduced the tumor volume and weight. And Silybin displayed obviously reduced the proteins and mRNA of ALDH1A1, RARα, Ets1 and MMP9 expressions.Conclusion: Our results indicated that Silybin showed inhibition of prostate cancer and the mechanism was involving with downregulating ALDH1A1 expression, thereby inhibiting the activation of RARα and preventing the activation of Ets1 to inhibit the growth and invasion of prostate cancer.
研究领域:
肿瘤学
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药理学
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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
Cancer Genomics & Proteomics
·
2026
·Vol. 23
·期 3
·407-429
·
IF 2.6
HANXUN YUE,ZENAN HU,GUOZHI WU,RENPENG LI,NA JIANG,YA ZHENG,YUPING WANG,YONGNING ZHOU
Background/Aim: Although aldehyde dehydrogenases 1 family member A1 (ALDH1A1) has been extensively studied in cancer, its role in hepatocellular carcinoma (HCC) remains poorly understood. This study was designed to characterize the expression pattern and functional roles of ALDH1A1 in HCC, and to further investigate its underlying molecular mechanisms using integrated proteomic analysis.
Materials and Methods: This study performed a pan-cancer analysis of ALDH1A1 expression, followed by validation of its expression levels in HCC tissue samples and cell lines. The expression of ALDH1A1 was manipulated using small interfering RNAs and lentiviral vector in HCC cell lines. And then the proliferation, migration, invasion, and tumorigenicity of HCC cells were observed in vitro and in vivo. Quantitative proteomic and phosphoproteomic profiling were conducted by liquid chromatography-tandem mass spectrometry, with comprehensive analyses and key findings validated by experiments.
Results: ALDH1A1 was highly expressed in HCC tissues but exhibited notable expression heterogeneity among HCC cell lines. Functionally, ALDH1A1 promoted the proliferation, migration, and tumorigenicity of HCC cells, while suppressing apoptosis and modestly attenuates invasion. Quantitative proteomic and phosphoproteomic analyses revealed that ALDH1A1 profoundly reshaped both protein expression and phosphorylation landscapes in HCC. Furthermore, we validated that ALDH1A1 positively regulates the expression of DMPK, PCMTD2, VAMP4, ARHGAP19, NOL4L, and ST7, while suppressing SLC31A1, DSTYK, CYP4F12, GPNMB expression. Rescue experiments indicated that ALDH1A1 may promote HCC via activating Rho family small GTPase. ALDH1A1 also significantly upregulated mTOR phosphorylation.
Conclusion: ALDH1A1 acts as an oncogenic driver and regulatory hub in HCC.
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DOI
PubMed
高影响因子
Translational Lung Cancer Research
·
2024
·Vol. 13
·期 10
·2698
·
IF 4
Ziying Zhao,Xiaoqing Feng,Huijuan Wu,Shuisheng Chen,Changsong Ma,Ziyun Guan,Luwen Lei,Kejing Tang,Xiao Chen,Yong Dong,Yubo Tang
Background Lung cancer is one of the most common malignant tumors worldwide. Despite advances in lung cancer treatment, patients still face challenges related to drug resistance and recurrence. Current methods for evaluating anti-cancer drug activity are insufficient, as they rely on two-dimensional (2D) cell culture and animal models. Therefore, the development of an in vitro drug evaluation model capable of predicting individual sensitivity to anti-cancer drugs would greatly enhance the success rate of drug treatments for lung cancer patients. The purpose of this research is to utilise conditional reprogramming technology to cultivate patient-derived lung cancer cells and to construct an in vitro 3D culture model using sodium alginate (SA) and gelatin. The aim is to study the biological characteristics of cells in the 3D culture model and to further investigate the sensitivity of anti-cancer drugs based on the alginate-gelatin 3D culture model. This approach provides new means and insights for personalized precision anti-cancer therapy and the development of new anti-cancer drugs. Methods Conditional reprogramming technology was used to generate conditionally reprogrammed lung adenocarcinoma cells (CRLCs). Alginate-gelatin hydrogel micro-beads were created to explore their potential use in the assessment of anti-cancer drugs. Cell proliferation was also examined using the MTS assay method. Live/dead staining was performed to estimate cell distribution and viability using calcein acetoxymethyl ester/propidium iodide (calcein-AM/PI) double staining. Protein expression was assessed by Western blot. Results The cells grown in the three-dimensional (3D) culture were in a state of continuous proliferation, and there was an obvious phenomenon of cell mass growth. The drug sensitivity assay results demonstrated that compared with the 2D-grown cells, the CRLCs grown in the alginate-gelatin hydrogel micro-beads exhibited more resistance to anti-cancer drugs. The results also showed that the 3D-cultured CRLCs showed greater protein expression levels of stem cell hallmarks, such as Nanog Homeobox (NANOG), SRY-Box Transcription Factor 2 (SOX-2), and aldehyde dehydrogenase 1 family member A1 (ALDH1A1), than the 2D-grown cells. Conclusions These findings suggest that the 3D hydrogel cell culture models more closely mimicked the in vivo biological and clinical behavior of cells, and demonstrated higher innate resistance to anti-cancer drugs than the 2D cell culture models, and thus could serve as valuable tools for diagnosis, drug screening, and personalized medicine.
研究领域:
肿瘤学
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药理学
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生物技术
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Foods
·
2024
·Vol. 13
·期 5
·737
·
IF 4.7
Jianhao Li,Zihang Shi,Xiankang Fan,Lihui Du,Qiang Xia,Changyu Zhou,Yangying Sun,Baocai Xu,Daodong Pan
The effects of low-sodium salt mixture substitution on the sensory quality, protein oxidation, and hydrolysis of air-dried chicken and its molecular mechanisms were investigated based on tandem mass tagging (TMT) quantitative proteomics. The composite salt formulated with 1.6% KCl, 0.8% MgCl2, and 5.6% NaCl was found to improve the freshness and texture quality scores. Low-sodium salt mixture substitution significantly decreased the carbonyl content (1.52 nmol/mg), surface hydrophobicity (102.58 μg), and dimeric tyrosine content (2.69 A.U.), and significantly increased the sulfhydryl content (74.46 nmol/mg) and tryptophan fluorescence intensity, suggesting that protein oxidation was inhibited. Furthermore, low-sodium salt mixture substitution significantly increased the protein hydrolysis index (0.067), and cathepsin B and L activities (102.13 U/g and 349.25 U/g), suggesting that protein hydrolysis was facilitated. The correlation results showed that changes in the degree of protein hydrolysis and protein oxidation were closely related to sensory quality. TMT quantitative proteomics indicated that the degradation of myosin and titin as well as changes in the activities of the enzymes, CNDP2, DPP7, ABHD12B, FADH2A, and AASS, were responsible for the changes in the taste quality. In addition, CNDP2, ALDH1A1, and NMNAT1 are key enzymes that reduce protein oxidation. Overall, KCl and MgCl2composite salt substitution is an effective method for producing low-sodium air-dried chicken.
研究领域:
食品科学
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蛋白质组学
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感官评价
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）