MYB原癌基因类似物2(MYBL2)作为MYB转录因子家族的一员,几乎在所有细胞中表达,但表达失调时具有致癌作用。MYBL2表达失调与癌细胞的细胞周期失调、无限增殖、凋亡逃避、转移扩散、细胞衰老及治疗抵抗等相关。同时,MYBL2通过调节上皮间...MYB原癌基因类似物2(MYBL2)作为MYB转录因子家族的一员,几乎在所有细胞中表达,但表达失调时具有致癌作用。MYBL2表达失调与癌细胞的细胞周期失调、无限增殖、凋亡逃避、转移扩散、细胞衰老及治疗抵抗等相关。同时,MYBL2通过调节上皮间质转化(epithelial to mesenchymal transition, EMT)及肿瘤免疫微环境,从而影响患者的预后。MYBL2及其下游转录参与基因有望成为癌症治疗的有效靶点,本文概述了MYBL2失调致癌机制及其在恶性肿瘤中的研究进展,以期为恶性肿瘤的靶向治疗和研究其浸润、转移的分子机制提供理论基础。展开更多
Background Undernutrition disrupts pregnant ewe's metabolic homeostasis and severely inhibits fetal growth and development.In this study,undernourished and nutrition-recovery pregnant sheep models and rumen epithe...Background Undernutrition disrupts pregnant ewe's metabolic homeostasis and severely inhibits fetal growth and development.In this study,undernourished and nutrition-recovery pregnant sheep models and rumen epithelial cells were utilized to investigate the mechanisms behind undernutrition-induced disruptions in male fetal rumen metabolism and development.Results Maternal undernutrition significantly reduced male fetal rumen weight and papilla length,width and surface area.Maternal undernutrition extremely suppressed nutrient metabolism and energy production in male fetal rumen via JAK3/STAT3 signaling to inhibit cell cycle progression and male fetal rumen development,while maternal nutritional recovery partially restored metabolic inhibition but failed to alleviate male fetal rumen development.Meanwhile,64 differentially expressed miRNAs(DEMs)were identified in male fetal rumen between undernourished ewes and controls.Novel miR-736 was overexpressed both in male fetal rumen of undernourished and nutrition-recovery models.E2F transcription factor 2(E2F2)and MYB proto-oncogene like 2(MYBL2)were the intersection of male fetal rumen differentially expressed genes(DEGs)and DEMs target genes integrated analysis and were predicted as novel miR-736 target genes.Further,we confirmed that novel miR-736 targeted and downregulated E2F2 and MYBL2 expression levels.Silencing E2F2 and MYBL2 promoted apoptosis and inhibited S-phase entry in rumen epithelial cells.Conclusions In summary,maternal undernutrition disrupted male fetal rumen metabolism and elevated novel miR-736,which targeted and downregulated E2F2 and MYBL2 to inhibit cell cycle progression and promote apoptosis,finally inhibited male fetal rumen development.This study provides new insights into the epigenetic mechanisms underlying maternal undernutrition-induced male fetal rumen developmental deficits.展开更多
成髓细胞瘤转录因子第2亚型(MYB proto-oncogene like 2, MYBL2)是MYB转录因子家族的成员,参与多种细胞的增殖、分化、凋亡。近年来,MYBL2作为一种转录调节因子,被发现其在肿瘤、炎性疾病等疾病中具有重要作用。一方面,MYBL2直接与启动...成髓细胞瘤转录因子第2亚型(MYB proto-oncogene like 2, MYBL2)是MYB转录因子家族的成员,参与多种细胞的增殖、分化、凋亡。近年来,MYBL2作为一种转录调节因子,被发现其在肿瘤、炎性疾病等疾病中具有重要作用。一方面,MYBL2直接与启动子结合区域结合,另一种通过与其他蛋白质相互作用结合。随着研究的深入,MYBL2在恶性肿瘤中的调控作用及分子机制逐步被揭示,但在不同肿瘤中的调控效应不尽相同。现在还需进一步研究MYBL2在各种恶性肿瘤中的调节机制,在未来MYBL2有成为恶性肿瘤的治疗靶点可能。本文根据近年恶性肿瘤中MYBL2的作用及其分子机制展开综述,为今后的研究提供新思路。MYB proto-oncogene like 2 (MYBL2) is a member of the MYB transcription factor family and is involved in the proliferation, differentiation and apoptosis of various cells. In recent years, MYBL2, as a transcriptional regulator, has been found to play an important role in tumors, inflammatory diseases and other diseases. On one hand, MYBL2 binds directly to promoter binding regions, and the other binds by interacting with other proteins. With the deepening of research, the regulatory role and molecular mechanism of MYBL2 in malignant tumors have been gradually revealed, but the regulatory effect in different tumors is not the same. It is still necessary to further study the regulatory mechanism of MYBL2 in various malignant tumors, and MYBL2 may become a therapeutic target for malignant tumors in the future. In this paper, we reviewed the role and molecular mechanism of MYBL2 in malignant tumors in recent years, providing new ideas for future research.展开更多
文摘MYB原癌基因类似物2(MYBL2)作为MYB转录因子家族的一员,几乎在所有细胞中表达,但表达失调时具有致癌作用。MYBL2表达失调与癌细胞的细胞周期失调、无限增殖、凋亡逃避、转移扩散、细胞衰老及治疗抵抗等相关。同时,MYBL2通过调节上皮间质转化(epithelial to mesenchymal transition, EMT)及肿瘤免疫微环境,从而影响患者的预后。MYBL2及其下游转录参与基因有望成为癌症治疗的有效靶点,本文概述了MYBL2失调致癌机制及其在恶性肿瘤中的研究进展,以期为恶性肿瘤的靶向治疗和研究其浸润、转移的分子机制提供理论基础。
基金supported by the National Natural Science Foundation of China(32402767)National Key Research and Development Program of China(2022YFD1301102)+3 种基金Anhui Province Natural Science Foundation Youth Project(2308085QC104)AAU Introduction of High-level Talent Funds(RC392107)Key Laboratory of Utilization of Livestock and Forage Resources in Circum-Tarim Region(Co-construction by Ministry and Province),Ministry of Agriculture and Rural Affairs(BSGJSYS202502)the China Agriculture Research System(CARS-38)。
文摘Background Undernutrition disrupts pregnant ewe's metabolic homeostasis and severely inhibits fetal growth and development.In this study,undernourished and nutrition-recovery pregnant sheep models and rumen epithelial cells were utilized to investigate the mechanisms behind undernutrition-induced disruptions in male fetal rumen metabolism and development.Results Maternal undernutrition significantly reduced male fetal rumen weight and papilla length,width and surface area.Maternal undernutrition extremely suppressed nutrient metabolism and energy production in male fetal rumen via JAK3/STAT3 signaling to inhibit cell cycle progression and male fetal rumen development,while maternal nutritional recovery partially restored metabolic inhibition but failed to alleviate male fetal rumen development.Meanwhile,64 differentially expressed miRNAs(DEMs)were identified in male fetal rumen between undernourished ewes and controls.Novel miR-736 was overexpressed both in male fetal rumen of undernourished and nutrition-recovery models.E2F transcription factor 2(E2F2)and MYB proto-oncogene like 2(MYBL2)were the intersection of male fetal rumen differentially expressed genes(DEGs)and DEMs target genes integrated analysis and were predicted as novel miR-736 target genes.Further,we confirmed that novel miR-736 targeted and downregulated E2F2 and MYBL2 expression levels.Silencing E2F2 and MYBL2 promoted apoptosis and inhibited S-phase entry in rumen epithelial cells.Conclusions In summary,maternal undernutrition disrupted male fetal rumen metabolism and elevated novel miR-736,which targeted and downregulated E2F2 and MYBL2 to inhibit cell cycle progression and promote apoptosis,finally inhibited male fetal rumen development.This study provides new insights into the epigenetic mechanisms underlying maternal undernutrition-induced male fetal rumen developmental deficits.
文摘成髓细胞瘤转录因子第2亚型(MYB proto-oncogene like 2, MYBL2)是MYB转录因子家族的成员,参与多种细胞的增殖、分化、凋亡。近年来,MYBL2作为一种转录调节因子,被发现其在肿瘤、炎性疾病等疾病中具有重要作用。一方面,MYBL2直接与启动子结合区域结合,另一种通过与其他蛋白质相互作用结合。随着研究的深入,MYBL2在恶性肿瘤中的调控作用及分子机制逐步被揭示,但在不同肿瘤中的调控效应不尽相同。现在还需进一步研究MYBL2在各种恶性肿瘤中的调节机制,在未来MYBL2有成为恶性肿瘤的治疗靶点可能。本文根据近年恶性肿瘤中MYBL2的作用及其分子机制展开综述,为今后的研究提供新思路。MYB proto-oncogene like 2 (MYBL2) is a member of the MYB transcription factor family and is involved in the proliferation, differentiation and apoptosis of various cells. In recent years, MYBL2, as a transcriptional regulator, has been found to play an important role in tumors, inflammatory diseases and other diseases. On one hand, MYBL2 binds directly to promoter binding regions, and the other binds by interacting with other proteins. With the deepening of research, the regulatory role and molecular mechanism of MYBL2 in malignant tumors have been gradually revealed, but the regulatory effect in different tumors is not the same. It is still necessary to further study the regulatory mechanism of MYBL2 in various malignant tumors, and MYBL2 may become a therapeutic target for malignant tumors in the future. In this paper, we reviewed the role and molecular mechanism of MYBL2 in malignant tumors in recent years, providing new ideas for future research.
