Journal of Genetics and Genomics
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2021
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IF 4.275
Shunqi Pei,Xuehui Wang,Xuan Wang,Hao Huang,Huaping Tao,Binghua Xie,Aifen Yang,Mengsheng Qiu,Zhou Tan
Glioma is the most common type of tumor in the central nervous system, accounting for around 80% of all malignant brain tumors. Previous studies showed a significant association between nuclear morphology and the malignant progress of gliomas. By virtue of integrated proteomics and genomics analyses as well as experimental validations, we identify three nuclear lamin genes ( LMNA , LMNB1 , and LMNB2 ) that are significantly upregulated in glioma tissues compared with normal brain tissues. We show that elevated expressions of LMNB1 , LMNB2 , and LMNA in glioma cells are highly associated with the rapid progression of the disease and the knockdown of LMNB1 , LMNB2 , and LMNA dramatically suppresses glioma progression in both in vitro and in vivo mouse models. Moreover, the repression of glioma cell growth by lamin knockdown is mediated by the pRb-mediated G1-S inhibition. On the contrary, overexpression of lamins in normal human astrocytes dramatically induced nuclear morphological aberrations and accelerated cell growth. Together, our multi-omics-based analysis has revealed a previously unrecognized role of lamin genes in gliomagenesis, providing a strong support for the key link between aberrant tumor nuclear shape and the survival of glioma patients. Based on these findings, lamins are proposed to be potential oncogene targets for therapeutic treatments of brain tumors.
研究领域:
神经科学
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肿瘤学
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分子生物学
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基因组学
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蛋白质组学
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产品关联
DOI
PubMed
高影响因子
Autophagy
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2018
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IF 11.1
Zhen Yang,Qi Sun,Junfei Guo,Shixing Wang,Ge Song,Weiying Liu,Min Liu,Hua Tang
Emerging evidence has revealed that miRNAs could upregulate the expression levels of target genes. However, the molecular mechanism underlying upregulation of targets mediated by miRNAs remains unclear. In this study, we found a novel miRNA named MIR-G-1 by GRSF1-RNA immunoprecipitation (RIP)-deep sequencing, which could directly target and upregulate LMNB1 and TMED5 in a GRSF1-dependent manner in cervical cancer cells. In addition, upregulated MIR-G-1 in cervical cancer promoted a malignant phenotype in vitro and in vivo. TMED5 could interact with WNT7B and thus activated the canonical WNT-CTNNB1/β-catenin signaling pathway. MIR-G-1 mediated the activation of this pathway. Furthermore, MIR-G-1 promoted serum starvation-induced nuclear macroautophagy/autophagy, and accelerated taxol (TAX)-induced DNA-damage repair in cervical cancer cells. Collectively, these findings may provide a new insight into the upregulation mechanism and nuclear autophagy mediated by miRNAs and provide a potential biomarker for cervical cancer.Abbreviations: 3ʹUTR: 3′ untranslated region; EMSA: electrophoretic mobility shift assay; EMT: epithelial-mesenchymal transition; GRSF1: G-rich RNA sequence binding factor 1; IF: immunofluorescence; IP: immunoprecipitation; IHC: immunohistochemistry; lnc: long noncoding; miRNA:microRNA; TAX: taxol; TMED5: transmembrane p24 trafficking protein 5
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
Advanced Science
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2024
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IF 14.3
Fugang Liu,Jiaqing Liu,Yang Luo,Siyi Wu,Xu Liu,Haoran Chen,Zhewen Luo,Haitao Yuan,Feng Shen,Fangfang Zhu,Jian Ye
Metabolic dysregulation is a key driver of cellular senescence, contributing to the progression of systemic aging. The heterogeneity of senescent cells and their metabolic shifts are complex and unexplored. A microfluidic SlipChip integrated with surface-enhanced Raman spectroscopy (SERS), termed SlipChip-SERS, is developed for single-cell metabolism analysis. This SlipChip-SERS enables compartmentalization of single cells, parallel delivery of saponin and nanoparticles to release intracellular metabolites and to realize SERS detection with simple slipping operations. Analysis of different cancer cell lines using SlipChip-SERS demonstrated its capability for sensitive and multiplexed metabolic profiling of individual cells. When applied to human primary fibroblasts of different ages, it identified 12 differential metabolites, with spermine validated as a potent inducer of cellular senescence. Prolonged exposure to spermine can induce a classic senescence phenotype, such as increased senescence-associated β-glactosidase activity, elevated expression of senescence-related genes and reduced LMNB1 levels. Additionally, the senescence-inducing capacity of spermine in HUVECs and WRL-68 cells is confirmed, and exogenous spermine treatment increased the accumulation and release of H 2 O 2 . Overall, a novel SlipChip-SERS system is developed for single-cell metabolic analysis, revealing spermine as a potential inducer of senescence across multiple cell types, which may offer new strategies for addressing ageing and ageing-related diseases.
研究领域:
生物技术
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细胞生物学
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老年学
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代谢组学
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微流控技术
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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）