JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
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2026
·Vol. 45
·期 1
·103
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IF 14.3
Bai Guannan,Zhang Lin,Zhao Manli,Zhang Jingyao,Chen Wenhao
Background Osteosarcoma (OS) is an aggressive bone malignancy in adolescents, with poor prognosis and limited survival improvement over decades, necessitating new therapeutic targets. Prior research identified Leucyl-tRNA synthetase (LARS) as critical for OS proliferation, prompting this investigation into its underlying mechanisms. Method Utilizing clinical OS samples, we assessed LARS and primase p58 subunit 2 (PRIM2) expression via immunohistochemistry. In vitro studies employed OS cell lines for LARS/PRIM2 overexpression or knockdown, followed by functional assays: MTT, colony formation, EdU staining, Transwell migration/invasion, and flow cytometry for cell cycle/ROS/Ca 2 ⁺ analysis. Xenograft models were used to evaluate tumor progression in vivo . Multi-omics analyses included transcriptome sequencing, proteomic profiling, and telomeric repeat amplification protocol-PCR to assess translational regulation. Stable isotope labeling by amino acids in cell culture (SILAC) determined leucine-dependent PRIM2 synthesis. Mechanisms were further probed using inhibitors and rescue experiments. Results LARS expression is significantly elevated in OS, and its overexpression enhances proliferation but inhibits invasion and migration in vitro and in vivo . Conversely, LARS silencing in OS cells results in cell cycle arrest. Mechanistically, the upregulation of LARS in OS is associated with increased glycolysis and DNA replication and a reduction in endoplasmic reticulum stress, while elevating the oncogene PRIM2 through leucine-dependent translational control. Conclusion Our findings highlight the crucial oncogenic role of the LARS/PRIM2 axis in promoting the pathogenesis of OS, primarily through the alleviation of endoplasmic reticulum stress and the activation of translation processes.
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高影响因子
SCIENTIA HORTICULTURAE
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2024
·
IF 3.9
Linmu Chen,Jingna Yan,Yiwen Miu,Rui Huang,Hao Wei,Lilei Wang,Cheng Zhang,Lianyu Yuan,Huarong Tong
The distinct qualities of etiolated leaves from chlorotic tea cultivars are significantly related to their developmental stages during harvesting. In this study, Hjy ( Camellia sinensis L. cv . Huangjinye) as a light sensitive etiolated tea variety had a higher concentration of theanine (99.36 mg/g) and lower total catechins (119.15 mg/g) than normal green tea plant. The shading treatment could turn the yellow leaves to green and alter the levels of catechins, caffeine, and theanine of tea shoots in Hjy. Additionally, the buds and 2nd leaves of Hjy tea shoots had the highest content of theanine, whereas the 3rd leaves contained the highest caffeine and total catechins. Moreover, the three different developmental stages of Hjy tea leaves had different levels of pigments, total free amino acids, total polyphenols, and soluble protein. Transcriptome and metabolome analyses identified a total of 58,175 genes and 414 metabolites in the three developmental stages, which were most enriched in photosynthesis, primary metabolism, lipid metabolism, and flavonoid metabolism. The multi-omics analysis revealed that the accumulations of L- glutamic acid and L-glutamine were up-regulated by GOGATs and GDHs and down-regulated by GSs, TS , and ALaDC. WRKY24, WRKY27, MYB105, and some other genes related to plant development and ion balance were highly correlated with L- glutamic acid biosynthesis. The decreased expressions of LARs and ANRs contributed to the reduction of catechin, epigallocatechin, and epigallocatechin gallate. WRKY35 , W RKY53, MYB62 , and some other genes related to photosynthesis, plant development, monooxygenases, and glycosylation exhibit roles in regulating catechins biosynthesis. This study provided the novel information about the Hjy tea plant, and the integrated strategy of multi-omics allowed a mechanistic understanding of the differential accumulation of L- glutamic acid and catechins during the development of etiolated tea leaves.
研究领域:
植物科学
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分子生物学
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农学
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茶学
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高影响因子
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