Identification of a New
            <i>GLDC</i>
            Gene Alternative Splicing Variant and its Protumorigenic Roles in Lung Cancer

Yuan, Yingli; Sun, Luguo; Wang, Xu; Chen, Jingxian; Jia, Mingnan; Zou, Yunlong; Sa, Huanlan; Cai, Yangyang; Xu, Yinghui; Sun, Chao; Guo, Ye; Li, Hongwei; Ma, Kewei

doi:10.2217/fon-2019-0403

Cited by 8 publications

(4 citation statements)

References 23 publications

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“…GLDC, a key enzyme in the glycine cleavage system, is involved in glycine metabolism and the conversion of glycine into a one-carbon unit, thereby enhancing glucose metabolism, energy metabolism, and other metabolic processes [ 18 , 19 , 20 ]. Prior research demonstrates that elevated expression of GLDC boosts cell proliferation, reinforces cell antioxidant capacity, improves cell survival, and significantly expedites the development of an organism’s tissues and organs [ 21 , 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Profiling Based at Different Time Points after Hatching Deepened Our Understanding on Larval Growth and Development of Amphioctopus fangsiao

Bao

Liu

et al. 2023

Metabolites

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As the quality of life improves, there is an increasing demand for nutrition-rich marine organisms like fish, shellfish, and cephalopods. To address this, artificial cultivation of these organisms is being explored along with ongoing research on their growth and development. A case in point is Amphioctopus fangsiao, a highly valued cephalopod known for its tasty meat, nutrient richness, and rapid growth rate. Despite its significance, there is a dearth of studies on the A. fangsiao growth mechanism, particularly of its larvae. In this study, we collected A. fangsiao larvae at 0, 4, 12, and 24 h post-hatching and conducted transcriptome profiling. Our analysis identified 4467, 5099, and 4181 differentially expressed genes (DEGs) at respective intervals, compared to the 0 h sample. We further analyzed the expression trends of these DEGs, noting a predominant trend of continuous upregulation. Functional exploration of this trend entailed GO and KEGG functional enrichment along with protein–protein interaction network analyses. We identified GLDC, DUSP14, DPF2, GNAI1, and ZNF271 as core genes, based on their high upregulation rate, implicated in larval growth and development. Similarly, CLTC, MEF2A, PPP1CB, PPP1R12A, and TJP1, marked by high protein interaction numbers, were identified as hub genes and the gene expression levels identified via RNA-seq analysis were validated through qRT-PCR. By analyzing the functions of key and core genes, we found that the ability of A. fangsiao larvae to metabolize carbohydrates, lipids, and other energy substances during early growth may significantly improve with the growth of the larvae. At the same time, muscle related cells in A. fangsiao larvae may develop rapidly, promoting the growth and development of larvae. Our findings provide preliminary insights into the growth and developmental mechanism of A. fangsiao, setting the stage for more comprehensive understanding and broader research into cephalopod growth and development mechanisms.

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Section: Discussionmentioning

confidence: 99%

Transcriptome Profiling Based at Different Time Points after Hatching Deepened Our Understanding on Larval Growth and Development of Amphioctopus fangsiao

Bao

Liu

et al. 2023

Metabolites

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“…Although GLDC has been demonstrated to participate in regulating the development of tumors in some types of cancers, its roles in different cancers are controversial and not always consistent. Previous studies have shown that GLDC overexpression or its gene alternative splicing enhances cellular transformation and tumorigenesis and is correlated with poorer survival in nonsmall cell lung cancer (NSCLC) (6,13). Inhibition of GLDC transcript represses cell proliferation and colony formation in NSCLC and prostate cancer cells (14,15).…”

Section: Discussionmentioning

confidence: 99%

GLDC mitigated by miR-30e regulates cell proliferation and tumor immune infiltration in TNBC

et al. 2022

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BackgroundTNBC, whose clinical prognosis is poorer than other subgroups of breast cancer, is a malignant tumor characterized by lack of estrogen receptors, progesterone hormone receptors, and HER2 overexpression. Due to the lack of specific targeted drugs, it is crucial to identify critical factors involved in regulating the progression of TNBC.MethodsWe analyzed the expression profiles of TNBC in TCGA and the prognoses values of GLDC. Correlations of GLDC and tumor immune infiltration were also identified. CCK8 and BrdU incorporation assays were utilized to determine cell proliferation. The mRNA and protein levels were examined by using Real-time PCR and Western blot analysis.ResultsIn the present study, we analyzed the mRNA expression profiles of TNBC in TCGA and found that GLDC, a key enzyme in glycine cleavage system, was significantly up-regulated in TNBC tissues and higher expression of GLDC was correlated with a worse prognosis in TNBC. Moreover, the expression of GLDC was negatively correlated with macrophage and monocyte and positively correlated with activated CD4 T cell and type 2 T helper cell in TNBC. Overexpression of GLDC facilitated the proliferation of TNBC cells, whereas GLDC knockdown had the opposite effects. Additionally, miR-30e acts as a functional upstream regulator of GLDC and the inhibitory effects of miR-30e on cell proliferation were mitigated by the reintroduction of GLDC.ConclusionsThese results imply that miR-30e-depressed GLDC acts as a tumor suppressive pathway in TNBC and provides potential targets for the treatment of TNBC.

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“…GLDC is the P protein in the glycine cleavage system and can be combined with glycine to transfer the methylamine group of glycine to the T protein [ 158 ]. GLDC participates in the first and rate-limiting step of glycine decomposition [ 157 ].…”

Section: Another Seven N-myc Target Genesmentioning

confidence: 99%

A Review of the Regulatory Mechanisms of N-Myc on Cell Cycle

Dong

Jin

et al. 2023

Molecules

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Neuroblastoma has obvious heterogeneity. It is one of the few undifferentiated malignant tumors that can spontaneously degenerate into completely benign tumors. However, for its high-risk type, even with various intensive treatment options, the prognosis is still unsatisfactory. At the same time, a large number of research data show that the abnormal amplification and high-level expression of the MYCN gene are positively correlated with the malignant progression, poor prognosis, and mortality of neuroblastoma. In this context, this article explores the role of the N-Myc, MYCN gene expression product on its target genes related to the cell cycle and reveals its regulatory network in promoting tumor proliferation and malignant progression. We hope it can provide ideas and direction for the research and development of drugs targeting N-Myc and its downstream target genes.

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Identification of a New GLDC Gene Alternative Splicing Variant and its Protumorigenic Roles in Lung Cancer

Cited by 8 publications

References 23 publications

Transcriptome Profiling Based at Different Time Points after Hatching Deepened Our Understanding on Larval Growth and Development of Amphioctopus fangsiao

Transcriptome Profiling Based at Different Time Points after Hatching Deepened Our Understanding on Larval Growth and Development of Amphioctopus fangsiao

GLDC mitigated by miR-30e regulates cell proliferation and tumor immune infiltration in TNBC

A Review of the Regulatory Mechanisms of N-Myc on Cell Cycle

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