BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
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2025
·
IF 3.7
Yanxue Zhao,Xinpei Liu,Zining Wu,Guotao Ma,Quanli Gao,Jun Zheng,Chaoji Zhang
Rhabdomyosarcoma (RMS), a common malignant tumor in children, presents numerous challenges in clinical treatment. This study investigated the specific functions and regulatory mechanisms of distal-less homeobox 5 ( DLX5 ) in RMS. Data from TCGA, GEO and GEPIA databases were downloaded and analyzed. The effect of DLX5 and PAX3-FOXO1 on RMS cells was examined through cellular experiments. Binding activity between DLX5 and H3K9me2 was assessed using pull-down and chromatin immunoprecipitation-qPCR assays. Additionally, RMS model mice were constructed via xenotransplantation to validate the in vivo effects of DLX5 on RMS. The results revealed that DLX5 was upregulated in RMS tissues and increased in various RMS cell lines, particularly in alveolar RMS cell lines. DLX5 knockdown inhibited malignant biological behaviors. Besides, DLX5 expression was associated with myogenic differentiation of RMS cells. While the overexpression or knockdown of DLX5 did not affect PAX-FOXO1 expression. PAX3-FOXO1 knockdown reduced DLX5 expression, indicating that DLX5 act as a downstream effector of PAX3-FOXO1 . Mechanistically, PAX3-FOXO1 regulated DLX5 expression through KDM4B/H3K9me2 axis. In vitro experiments further demonstrated that knockout of DLX5 or KDM4B inhibited tumor growth. In conclusion, DLX5 expression was increased in PAX3-FOXO1 –driven RMS, and its knockdown inhibited malignant biological behaviors of RMS cells. Moreover, the aberrant expression of DLX5 in PAX3-FOXO1 –driven RMS was regulated by KDM4B/H3K9me2 axis. These findings provided potential therapeutic targets for RMS treatment.
研究领域:
分子生物学
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肿瘤学
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表观遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INVESTIGATIONAL NEW DRUGS
·
2023
·Vol. 41
·期 1
·134-141
·
IF 3.4
Yan Gaobo,Zhang Hongyan,Li Yan,Miao Guoqiang,Liu Xiaolei,Lv Qifan
Lysine-specific demethylase 1 (LSD1) has been a promising target to treat prostate cancer, and discovery of novel LSD1 inhibitors would have great clinical significance. In this work, viscosalactone B was first identified as a novel LSD1 inhibitor. Viscosalactone B isolated from Withania Somnifera displayed antiproliferative activity against PC3, DU145, C42B, PC3/MDVR, DU145/MDVR, and C42B/MDVR cells with IC 50 values of 1.17, 0.72, 3.86, 2.06, 0.96 and 1.15 μM, respectively. In comparison, it was a selective LSD1 inhibitor with an IC 50 value of 970.27 nM and could induce a significant accumulation of LSD1 substrates H3K9me1, H3K9me2, and H3K4me1 in a concentration-dependent manner in DU145 cells. According to docking studies, it formed hydrogen bonds with the Thr11, Lys14, and Arg8 residues of LSD1. Importantly, while it displayed potent antitumor efficacy in vivo, it did not show obvious cytotoxicity on the major organs of nude mice. Therefore, viscosalactone B, as a novel LSD1 inhibitor, is a potential candidate that can be used for the treatment of prostate cancer in clinics.
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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化学生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Cell and Developmental Biology
·
2021
·
IF 6.684
Sun Yan-Li,Wang Xue-Lin,Yang Lei-Lei,Ge Zhao-Jia,Zhao Yong,Luo Shi-Ming,Shen Wei,Sun Qing-Yuan,Yin Shen
Paraquat (PQ) is a widely used non-selective and oxidizing herbicide in farmland, orchards, flower nursery, and grassland. Overuse of PQ will accumulate in the body and affect the reproduction in mammals. In this study, we found that PQ could reduce the female fertility by oral administration for 21 days in mice. PQ exposure could impair the nuclear maturation by perturbing the spindle assembly and kinetochore–microtubule attachment to cause the misaligned chromosomes during meiosis. In the meantime, PQ exposure disturbed the mitochondrial distribution and enhanced the level of reactive oxygen species and early apoptosis, which thereby deteriorated the early embryo development. Also, PQ administration could cause some changes in epigenetic modifications such as the level of H3K9me2 and H3K27me3. Therefore, PQ administration reduces the female fertility by impairing the nuclear and cytoplasmic maturation of oocytes in mice.
研究领域:
生殖生物学
·
毒理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
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