分析MYBL2在弥漫大B细胞淋巴瘤 (diffuse large B-cell lymphoma,DLBCL)中的表达及临床意义。方法:选择诊断为DLBCL的病例样本共128例,列为研究组;另选择同时间段内28例淋巴结反应性增生组织,纳入对照组。两组样本均检测MYBL2表达,对比...分析MYBL2在弥漫大B细胞淋巴瘤 (diffuse large B-cell lymphoma,DLBCL)中的表达及临床意义。方法:选择诊断为DLBCL的病例样本共128例,列为研究组;另选择同时间段内28例淋巴结反应性增生组织,纳入对照组。两组样本均检测MYBL2表达,对比分析MYBL2在DLBCL中的表达水平及意义。结果:研究组的MYBL2表达水平显著高于对照组,差异有统计学意义(P<0.05)。DLBCL中不同免疫亚型中MYBL2表达的差异有统计学意义(P<0.05)。且MYBL2表达与C-myc表达呈正相关(rs=0.198,P=0.037<0.05)。结论:MYBL2在DLBCL中高表达,提示MYBL2可能参与DLBCL的生物过程。MYBL2 在non-GCB亚型DLBCL中表达更高,且与C-myc的表达呈正相关,提示MYBL2高表达可能与DLBCL差预后相关,可作为诊断弥漫大B细胞淋巴瘤的辅助手段,临床可进一步推广应用。展开更多
MYBL2(MYB proto-oncogene like 2)is an emerging prognostic marker for malignant tumors,and its potential role in osteosarcoma and its relationship with immune infiltration in pan-cancer is yet to be elucidated.We const...MYBL2(MYB proto-oncogene like 2)is an emerging prognostic marker for malignant tumors,and its potential role in osteosarcoma and its relationship with immune infiltration in pan-cancer is yet to be elucidated.We constructed a transcription factor activity profile of os-teosarcoma using the single-cell regulatory network inference algorithm based on single-cell RNA sequencing data obtained from the Gene Expression Omnibus.Subsequently,we calcu-lated the extent of MYBL2 activation in malignant proliferative osteoblasts.We also explored the association between MYBL2 and chemotherapy resistance in osteosarcoma.Furthermore,we systematically correlated MYBL2 with immunological signatures in the tumor microenviron-ment in pan-cancer,including immune cell infiltration,immune checkpoints,and tumor immu-notherapy prognosis.Finally,we developed and validated a risk score(MRGS),derived an osteosarcoma risk score nomogram based on MRGS,and tested its ability to predict prognosis.MYBL2 and gene enrichment analyses in osteosarcoma and pan-cancer revealed that MYBL2 was positively correlated with cell proliferation and tumor immune pathways.MYBL2 expres-sion positively correlated with SLC19A1 in pan-cancer and osteosarcoma cell lines.Pan-cancer immune infiltration analysis revealed that MYBL2 was correlated with myeloid-derived sup-pressor cells,Th2 cell infiltration,CD276,RELT gene expression,and tumor mutation burden.展开更多
Anthocyanin accumulation is recognized as a visible biomarker of plants that have suffered from environmental stresses. However, the molecular mechanisms underlying stress-induced anthocyanin biosynthesis remain uncle...Anthocyanin accumulation is recognized as a visible biomarker of plants that have suffered from environmental stresses. However, the molecular mechanisms underlying stress-induced anthocyanin biosynthesis remain unclear. Expression of anthocyanin-specific genes is regulated by the conserved MBW complex, which is composed of the MYB, bHLH, and WD40 subunRs in higher plants. MBW activity is repressed by MYBL2 and the JAZ family proteins, which bind competitively to bHLH and MYB/bHLH, respectively. Here, we found that MYBL2 and JAZs mediate gibberellic acid-inhibRed anthocyanin biosynthesis in Arabidopsis. Competitive pull-down and dual-lucifarase assays showed that DELLA proteins directly sequester MYBL2 and JAZ repressors, leading to the release of bHLH/MYB subunits and subsequently to the formation of active MBW complex, which then activates the anthocyanin biosynthetic pathway. The JAZ-DELLA-MYBL2 module also plays an Important role in abiotic stress-induced anthocy- anin biosynthesis. Furthermore, we found that the DELLA protein RGA accumulates upon plant exposure to abiotic stresses. Altogether, our data reveal that DELLA-promoted anthocyanin biosynthesis is mediated at least in part by MYBL2 and JAZ regulatory proteins, providing new insights into the coordinated regulation of plant growth and defense through metabolic pathway regulation.展开更多
Extensive studies in various plants show that the anthocyanin biosynthetic process is affected by environmental factors and regulated by many transcription factors through sophisticated regulatory networks. However, i...Extensive studies in various plants show that the anthocyanin biosynthetic process is affected by environmental factors and regulated by many transcription factors through sophisticated regulatory networks. However, it remains largely unclear about the roles of microRNA in this process. Here, we demonstrate that miR858a is a positive regulator of anthocyanin biosynthesis in Arabidopsis seedlings. Overexpression of miR858a enhances the accumulation of anthocyanins, whereas the reduced miR858a activity results in low levels of anthocyanins in STTM858 transgenic plants. We found that miR858a inhibits the expression of MYBL2, a key negative regulator of anthocyanin biosynthesis, by translational repression. In addition, ELONGATED HYPOCOTYL 5 （HYS） was shown to directly bind the MYBL2 promoter and represses its expression via specific histone modifications. Interestingly, we found that miR858a exhibits light- responsive expression in an HY5-dependent manner. Together, these results delineate the HY5- MIR858a-MYBL2 loop as a cellular mechanism for modulating anthocyanin biosynthesis, suggesting that integration of transcriptional and posttranscriptional regulation is critical for governing proper anthocyanin accumulation in response to light and other environmental factors.展开更多
基金supported by Changsha Natural Science Foundation,Hunan,China(No.kq2202382)the Natural Science Foundation of Hunan,China(No.2022JJ40802,2022JJ30928)the Project funded by China Postdoctoral Science Foundation(No.2022M713525).
文摘MYBL2(MYB proto-oncogene like 2)is an emerging prognostic marker for malignant tumors,and its potential role in osteosarcoma and its relationship with immune infiltration in pan-cancer is yet to be elucidated.We constructed a transcription factor activity profile of os-teosarcoma using the single-cell regulatory network inference algorithm based on single-cell RNA sequencing data obtained from the Gene Expression Omnibus.Subsequently,we calcu-lated the extent of MYBL2 activation in malignant proliferative osteoblasts.We also explored the association between MYBL2 and chemotherapy resistance in osteosarcoma.Furthermore,we systematically correlated MYBL2 with immunological signatures in the tumor microenviron-ment in pan-cancer,including immune cell infiltration,immune checkpoints,and tumor immu-notherapy prognosis.Finally,we developed and validated a risk score(MRGS),derived an osteosarcoma risk score nomogram based on MRGS,and tested its ability to predict prognosis.MYBL2 and gene enrichment analyses in osteosarcoma and pan-cancer revealed that MYBL2 was positively correlated with cell proliferation and tumor immune pathways.MYBL2 expres-sion positively correlated with SLC19A1 in pan-cancer and osteosarcoma cell lines.Pan-cancer immune infiltration analysis revealed that MYBL2 was correlated with myeloid-derived sup-pressor cells,Th2 cell infiltration,CD276,RELT gene expression,and tumor mutation burden.
文摘Anthocyanin accumulation is recognized as a visible biomarker of plants that have suffered from environmental stresses. However, the molecular mechanisms underlying stress-induced anthocyanin biosynthesis remain unclear. Expression of anthocyanin-specific genes is regulated by the conserved MBW complex, which is composed of the MYB, bHLH, and WD40 subunRs in higher plants. MBW activity is repressed by MYBL2 and the JAZ family proteins, which bind competitively to bHLH and MYB/bHLH, respectively. Here, we found that MYBL2 and JAZs mediate gibberellic acid-inhibRed anthocyanin biosynthesis in Arabidopsis. Competitive pull-down and dual-lucifarase assays showed that DELLA proteins directly sequester MYBL2 and JAZ repressors, leading to the release of bHLH/MYB subunits and subsequently to the formation of active MBW complex, which then activates the anthocyanin biosynthetic pathway. The JAZ-DELLA-MYBL2 module also plays an Important role in abiotic stress-induced anthocy- anin biosynthesis. Furthermore, we found that the DELLA protein RGA accumulates upon plant exposure to abiotic stresses. Altogether, our data reveal that DELLA-promoted anthocyanin biosynthesis is mediated at least in part by MYBL2 and JAZ regulatory proteins, providing new insights into the coordinated regulation of plant growth and defense through metabolic pathway regulation.
文摘Extensive studies in various plants show that the anthocyanin biosynthetic process is affected by environmental factors and regulated by many transcription factors through sophisticated regulatory networks. However, it remains largely unclear about the roles of microRNA in this process. Here, we demonstrate that miR858a is a positive regulator of anthocyanin biosynthesis in Arabidopsis seedlings. Overexpression of miR858a enhances the accumulation of anthocyanins, whereas the reduced miR858a activity results in low levels of anthocyanins in STTM858 transgenic plants. We found that miR858a inhibits the expression of MYBL2, a key negative regulator of anthocyanin biosynthesis, by translational repression. In addition, ELONGATED HYPOCOTYL 5 （HYS） was shown to directly bind the MYBL2 promoter and represses its expression via specific histone modifications. Interestingly, we found that miR858a exhibits light- responsive expression in an HY5-dependent manner. Together, these results delineate the HY5- MIR858a-MYBL2 loop as a cellular mechanism for modulating anthocyanin biosynthesis, suggesting that integration of transcriptional and posttranscriptional regulation is critical for governing proper anthocyanin accumulation in response to light and other environmental factors.
