Solution structure of human myeloid-derived growth factor suggests a conserved function in the endoplasmic reticulum

Bortnov, Valeriu; Tonelli, Marco; Lee, Woonghee; Lin, Ziqing; Annis, Douglas S.; Demerdash, Omar; Bateman, Alex; Mitchell, Julie C.; Ge, Ying; Markley, John L.; Mosher, Deane F.

doi:10.1038/s41467-019-13577-5

Cited by 20 publications

(20 citation statements)

References 61 publications

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“…C19orf10 is highly conserved in evolution and is mainly localized in the Golgi and endoplasmic reticulum, but it functions extracellularly [8]. The N-terminus and C-terminus of human C19orf10 contain a signal peptide and a conserved sequence of the endoplasmic reticulum, respectively, but human C19orf10 has no sequence homology with any other proteins [9]. Structural analysis has revealed that C19orf10 consists of 10 antiparallel β-strands forming a β-sandwich, and its folding topology is not similar to other cytokines or growth factors [10].…”

Section: Introductionmentioning

confidence: 99%

C19orf10 promotes malignant behaviors of human bladder carcinoma cells via regulating the PI3K/AKT and Wnt/β-catenin pathways

Li¹,

Mao²,

Zhao³

et al. 2021

J. Cancer

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Background:Chromosome 19 open reading frame 10 (C19orf10) is a myocardial repair mediator overexpressed in hepatocellular carcinoma. However, its function and clinical value in bladder cancer (BC) have not been reported. This study aimed to investigate the role of C19orf10 in BC progression and explore underlying mechanisms. Methods: C19orf10 expression in BC tissues and human BC cell lines was assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. The correlation between the C19orf10 protein levels determined by immunohistochemical staining and the clinicopathological characteristics of 192 BC patients was evaluated. BC cell lines SW780, J82 and UMUC-3 were transfected with small interfering RNA (siRNA) targeting C19orf10 or plasmids overexpressing C19orf10. Cell proliferation, migration and invasion were measured by Cell Counting Kit-8, Colony formation, EdU incorporation and Transwell assays. The effect of small hairpin RNA (shRNA)-mediated stable C19orf10 knockdown on tumor formation was assessed in a xenograft mouse model. The expressions of epithelial-mesenchymal transition (EMT) markers, PI3K/AKT and Wnt/β-catenin signaling pathways-related molecules were determined by western blot assay. Results: C19orf10 was significantly upregulated in the BC tissues and a panel of human BC cell lines. High expression of C19orf10 was positively associated with malignant behaviors in BC. C19orf10 knockdown inhibited cell proliferation, migration, and invasion in SW780 and J82 cells, while C19orf10 overexpression in UMUC-3 cells resulted in opposite effects. In addition, C19orf10 silence in SW780 cells suppressed tumor growth in xenograft mice. Moreover, C19orf10 promotes the malignant behaviors and EMT of human bladder carcinoma cells via regulating the PI3K/AKT and Wnt/β-catenin pathways. Conclusion: C19orf10 is overexpressed in BC and functions as an oncogenic driver that promotes cell proliferation and metastasis, and induces EMT of BC cells via mechanisms involving activation of the PI3K/AKT and Wnt/β-catenin pathways. This study provides valuable insight on targeting C19orf10 for BC treatment.

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Section: Introductionmentioning

confidence: 99%

C19orf10 promotes malignant behaviors of human bladder carcinoma cells via regulating the PI3K/AKT and Wnt/β-catenin pathways

Li¹,

Mao²,

Zhao³

et al. 2021

J. Cancer

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“…Here we use MYDGF (Myeloid Derived Growth Factor) as an example KO gene to illustrate this application of scTenifoldKnk. MYDGF , also known as C19orf10 , is a 142-residue protein broadly expressed in multiple tissues and cell types [79, 80]. Mydgf has been shown in a mouse model to enhance cardiac myocyte survival, tissue repair, and angiogenesis caused by myocardial infarction [81].…”

Section: Resultsmentioning

confidence: 99%

“…MYDGF , also known as C19orf10 , is a 142-residue protein broadly expressed in multiple tissues and cell types. 58,59 Mydgf has been shown in a mouse model to enhance cardiac myocyte survival, tissue repair, and angiogenesis caused by myocardial infarction. 60 To elucidate MYDGF ’s function, we downloaded multiple human scRNAseq data sets from the PanglaoDB database.…”

Section: Resultsmentioning

confidence: 99%

“…66 Identified functions were also related to promoting survival and growth, as previously reported. 60,[68][69][70] In summary, we used Mydgf as an example gene to demonstrate that scTenifoldKnk can be used to knock out a gene across multiple cell types in order to identify shared as well as cell typespecific functions of the KO gene.…”

Section: Results 7: Characterization Of a Multifunctional Gene Using Sctenifoldknk Following Systematic Ko Of The Gene In Multiple Cell Tmentioning

confidence: 99%

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scTenifoldKnk: an efficient virtual knockout tool for gene function predictions via single-cell gene regulatory network perturbation

Osorio

Zhong

et al. 2021

Preprint

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Gene knockout (KO) experiments are a proven approach for studying gene function. A typical KO experiment usually involves the phenotypic characterization of KO organisms. The recent advent of single-cell technology has greatly boosted the resolution of cellular phenotyping, providing unprecedented insights into cell-type-specific gene function. However, the use of single-cell technology in large-scale, systematic KO experiments is prohibitive due to the vast resources required. Here we present scTenifoldKnk, a machine learning workflow that performs virtual KO experiments using single-cell RNA sequencing (scRNA-seq) data. scTenifoldKnk first uses data from wild-type (WT) samples to construct a single-cell gene regulatory network (scGRN). Then, a gene is knocked out from the constructed scGRN by setting weights of the gene's outward edges to zeros. ScTenifoldKnk then compares this "pseudo-KO" scGRN with the original scGRN to identify differentially regulated (DR) genes. These DR genes, also called virtual-KO perturbed genes, are used to assess the impact of the gene KO and reveal the gene's function in analyzed cells. Using existing data sets, we demonstrate that the scTenifoldKnk analysis recapitulates the main findings of three real-animal KO experiments and confirms the functions of genes underlying three Mendelian diseases. We show the power of scTenifoldKnk as a predictive method to successfully predict the outcomes of two KO experiments that involve intestinal enterocytes in Ahr-/- mice and pancreatic islet cells in Malat1-/- mice, respectively. Finally, we demonstrate the use of scTenifoldKnk to perform systematic KO analyses, in which a large number of genes are virtually deleted, allowing gene functions to be revealed in a cell type-specific manner.

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“…This physiological event leads to an alteration in metabolic machinery accompanied by predominance of glycolysis and protection from damage by free radicals (20). This cellular stress is the main trigger for secretion of myeloid-derived growth factor (MYDGF) protein to act as a paracrine/autocrine survival factor, a notion that justi es upregulation of this protein in FT (21). It is the rst report of differential expression of MYDGF protein in FT and TP.…”

Section: Discussionmentioning

confidence: 99%

Proteome Profiling of Human Placenta Reveals Developmental Stage-Dependent Alterations in Protein Signature

Sarvestani¹,

Shojaeian

Vanaki

et al. 2021

Preprint

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Introduction Placenta is a complex organ that plays a significant role in the maintenance of pregnancy health. It is a dynamic organ that undergoes dramatic changes in growth and development at different stages of gestation. In the first-trimester, the conceptus develops in a low oxygen environment that favors organogenesis in the embryo and cell proliferation and angiogenesis in the placenta; later in pregnancy, higher oxygen concentration is required to support the rapid growth of the fetus. This transition, which appears unique to the human placenta, must be finely tuned through successive rounds of protein signature alterations. This study compares placental proteome in normal first-trimester (FT) and term human placentas (TP). MethodsNormal human first-trimester and term placental samples were collected and differentially expressed proteins were identified using two-dimensional liquid chromatography-tandem mass spectrometry.ResultsDespite the overall similarities, 120 proteins were differently expressed in first and term placentas. Out of these, 120 proteins, expression of 72 was up-regulated and that of 48 was down-regulated in the first when compared with the full term placentas. Twenty out of 120 differently expressed proteins were sequenced, among them seven showed increased (GRP78, PDIA3, ENOA, ECH1, PRDX4, ERP29, ECHM), eleven decreased (TRFE, ALBU, K2C1, ACTG, CSH2, PRDX2, FABP5, HBG1, FABP4, K2C8, K1C9) expression in first-trimester compared to the full-term placentas and two proteins exclusively expressed in first-trimester placentas (MESD, MYDGF). DiscussionAccording to Reactome and PANTHER softwares, these proteins were mostly involved in response to chemical stimulus and stress, regulation of biological quality, programmed cell death, hemostatic and catabolic processes, protein folding, cellular oxidant detoxification, coagulation and retina homeostasis. Elucidation of alteration in protein signature during placental development would provide researchers with a better understanding of the critical biological processes of placentogenesis and delineate proteins involved in regulation of placental function during development.

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Solution structure of human myeloid-derived growth factor suggests a conserved function in the endoplasmic reticulum

Cited by 20 publications

References 61 publications

C19orf10 promotes malignant behaviors of human bladder carcinoma cells via regulating the PI3K/AKT and Wnt/β-catenin pathways

C19orf10 promotes malignant behaviors of human bladder carcinoma cells via regulating the PI3K/AKT and Wnt/β-catenin pathways

scTenifoldKnk: an efficient virtual knockout tool for gene function predictions via single-cell gene regulatory network perturbation

Proteome Profiling of Human Placenta Reveals Developmental Stage-Dependent Alterations in Protein Signature

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