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As a newly discovered posttranslational modification (PTM), crotonylation has been identified in histone and nonhistone proteins and has important roles in the regulation of various diseases and biological processes. With the development of high-resolution mass spectrometry approaches, an increasing number of endogenous crotonylation has been detected and identified. The discovery of crotonylation regulatory enzymes paved the way for the study of crotonylation mechanism. In this review, we summarize the biological functions and regulatory mechanism of crotonylation in eukaryotes and introduce the recent progress on crotonylation in malignant tumor.
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Hypoxic preconditioning could improve the survival of mesenchymal stem cells (MSCs) in ischemic or hypoxic environments, but its exact mechanism remains to be further explored. This study aims to determine the role of lysine crotonylation (Kcr) in regulating the survival and proliferation of peripheral blood mesenchymal stem cells (PBMSCs) in the hypoxic culture. PBMSCs were isolated and cultured from rat peripheral blood mononuclear cells, and their surface markers were identified by flow cytometry. PBMSCs were first subjected to hypoxic/ normoxic preconditioning: hypoxic (1% O
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Objective: To investigate the effects of bromodomain-containing protein 4 (BRD4) inhibitor I-BET762 on histone crotonylation, proliferation and migration of prostate cancer cells. Methods: Three human prostate cancer cell lines, i.e., LNCaP, C4-2B and PC-3, were respectively treated with I-BET762 of half maximal inhibitory concentration. Histone crotonylation modification and acetylase expression were detected by Western blotting. CCK-8, transwell migration test and scratch test were used to detect the effects of I-BET762 on proliferation and migration of LNCaP, C4-2B and PC-3 cells. Results: I-BET762 inhibited the expression of histone acetylase P300 and GCN5, and reduced the histone crotonylation modification. Transwell migration test and scratch test showed that I-BET762 could inhibit the migration of prostate cancer cell lines LNCaP, C4-2B and PC-3 (all P<0.01); CCK-8 test showed that the proliferation of three prostate cancer cell lines was inhibited by I-BET762. Conclusion: In prostate cancer cells, I-BET762 can reduce the histone crotonylation and also inhibit cell proliferation and migration.
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Objective • To study whether lysine crotonylation can be used as a candidate biomarker for prostate cancer diagnosis, and its correlation with clinical stages and pathologic grades. Methods • Seventy-three cases of tumor and 7 normal prostate tissues were included in the study. The global levels of lysine crotonylation and histone H4 acetylation were detected in each sample by immunohistochemistry. Statistical comparison and correlation analysis were performed. Results • Compared with normal prostate tissue, the global level of lysine crotonylation was significantly reduced in prostate cancer tissue (P=0.001), while histone H4 acetylation levels were close to each other in two groups (P=0.704). No statistical difference in the levels of lysine crotonylation or histone H4 acetylation were found in different clinical stages and pathologic grades (P>0.05). There was no correlation between histone H4 acetylation and clinical stages or pathologic grades of prostate cancer. There was a positive correlation between lysine crotonylation and the grading of prostate cancer (r=0.493, P=0.000). Conclusion • Compared to histone H4 acetylation, lysine crotonylation is a better candidate biomarker to diagnose prostate cancer.