THBS1 Is a Novel Serum Prognostic Factors of Acute Myeloid Leukemia

Zhu, Lifei; Li, Qiong; Wang, Xiaoguo; Liao, Jun; Zhang, Wei; Gao, Lei; Liu, Yao; Zhang, Cheng; Zhang, Xi; Rao, Jun; Kong, Peiyan

doi:10.3389/fonc.2019.01567

Cited by 27 publications

(14 citation statements)

References 36 publications

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“…Bone is a primary site for breast cancer metastases, and patients often suffer from osteolytic bone metastases, which is incurable [ 16 ]. Previously, we conducted integrated bioinformatics analysis to find several possible key genes which are related with bone metastasis [ 13 ]. Currently, we used same gene dataset, expanding to find differential LncRNAs which are associated with bone metastasis, and further elucidate more possible LncRNA-mRNA interaction pairs.…”

Section: Discussionmentioning

confidence: 99%

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New insight into long non-coding RNAs associated with bone metastasis of breast cancer based on an integrated analysis

Huang¹,

Liu²,

Chen³

et al. 2021

Cancer Cell Int

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Background Bone is the most common site of metastatic breast cancer, and it is a leading cause of breast cancer-related death. This study aimed to explore bone metastasis-related long non-coding RNAs (lncRNAs) in breast cancer. Methods Four mRNA datasets and two lncRNA datasets of bone metastasis, lung metastasis and liver metastasis of breast cancer were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) in group of bone metastasis vs lung metastasis and bone metastasis vs liver metastasis, as well as the overlap of the two groups, were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and protein–protein interaction (PPI) network construction of DEmRNAs were conducted. The cis nearby-targeted DEmRNAs of DElncRNAs were obtained. Quantitative real-time polymerase chain reactions (qRT-PCR) was used to detect the expression levels of selected DEmRNAs and DElncRNAs. LOC641518-lymphoid enhancer-binding factor 1 (LEF1) pair was selected to verify its role in migration and invasion capability of breast cancer cells by wounding healing assay and transwell invasion assay. Results A total of 237 DEmRNAs were obtained in bone metastasis compared with both lung metastasis and liver metastasis. A total of three DElncRNAs in bone metastasis compared with both lung metastasis and liver metastasis were obtained. A total of seven DElncRNA-nearby-targeted DEmRNA pairs and 15 DElncRNA-nearby-targeted DEmRNA pairs in group of bone metastasis vs lung metastasis and bone metastasis vs liver metastasis, were detected, respectively. Four cis LncRNA-mRNA interaction pairs were identified, which are LOC641518-LEF1, FLJ35024-Very Low Density Lipoprotein Receptor (VLDLR), LOC285972-Retinoic Acid Receptor Responder 2 (RARRES2) and LOC254896-TNF receptor superfamily member 10c (TNFRSF10C). qRT-PCR using clinical samples from our hospital confirms the bioinformatics prediction. siRNA knocking down LOC641518 down-regulates LEF1 mRNA expression, and reduces the migration and invasion capability of breast cancer cells. Conclusions We concluded that four LncRNA-mRNA pairs, including LOC641518-LEF1, may play a central role in breast cancer bone metastasis.

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Section: Discussionmentioning

confidence: 99%

“…Ethical approval was obtained from the ethics committee of the First People’s Hospital of Chengdu and informed written consent was obtained from all of subjects. All the patients in the current study were same as described in the previous publication [ 13 ].…”

Section: Methodsmentioning

confidence: 99%

New insight into long non-coding RNAs associated with bone metastasis of breast cancer based on an integrated analysis

Huang¹,

Liu²,

Chen³

et al. 2021

Cancer Cell Int

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“…THBS1 is known to inhibit cell growth and to induce myeloid differentiation of the promyelocytic AML cell line HL-60 [ 43 ]. It has also been shown that THBS1 is lowly expressed in AML patients [ 44 ]. MMP8 gene encodes the metalloproteinase 8.…”

Section: Discussionmentioning

confidence: 99%

A novel leukemic route of mutant NPM1 through nuclear import of the overexpressed long noncoding RNA LONA

Gourvest

Clara

et al. 2021

Leukemia

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The most frequent genetic alteration in acute myeloid leukemia (AML) is the mutation of nucleophosmin 1 (NPM1). Yet, its downstream oncogenic routes are not fully understood. Here, we report the identification of one l ong noncoding RNA (lncRNA) o verexpressed in N PM1-mutated A ML patients (named LONA) whose intracellular localization inversely reflects that of NPM1. While NPM1 is nuclear and LONA cytoplasmic in wild-type NPM1 AML cells, LONA becomes nuclear as mutant NPM1 moves toward the cytoplasm. Gain or loss of function combined with a genome-wide RNA-seq search identified a set of LONA mRNA targets encoding proteins involved in myeloid cell differentiation (including THSB1, MAFB, and ASB2) and interaction with its microenvironment. Consistently, LONA overexpression in mutant NPM1 established cell lines and primary AML cells exerts an anti-myeloid differentiation effect, whilst it exerts an opposite pro-myeloid differentiation effect in a wild type NPM1 setting. In vivo, LONA overexpression acts as an oncogenic lncRNA reducing the survival of mice transplanted with AML cells and rendering AML tumors more resistant to AraC chemotherapy. These data indicate that mutation-dependent nuclear export of NPM1 leads to nuclear retention and consequent oncogenic functions of the overexpressed lncRNA LONA, thus uncovering a novel NPM1 mutation-dependent pathway in AML pathogenesis.

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“…Such quantitative differences in the release of extracellular regulators may contribute to the previously described differences among various stem cell niches in their regulation of normal hematopoiesis [ 3 ]. Many of the extracellular regulators involved in normal hematopoiesis are also important in leukemic hematopoiesis although their function in leukemic hematopoiesis is less well characterized; e.g., collagen/integrin/Rac1 [ 56 , 57 ], the CDH1 [ 58 ] and CDH2 cadherins [ 59 ], thrombospondin [ 60 , 61 ], TGFβ [ 62 , 63 , 64 ], osteopontin [ 65 ] and LOX/lipid metabolism [ 66 , 67 ] all seem to be important for leukemogenesis and/or chemosensitivity in hematological malignancies.…”

Section: Discussionmentioning

confidence: 99%

The Extracellular Bone Marrow Microenvironment—A Proteomic Comparison of Constitutive Protein Release by In Vitro Cultured Osteoblasts and Mesenchymal Stem Cells

Aasebø

Birkeland

Selheim

et al. 2020

Cancers

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Mesenchymal stem cells (MSCs) and osteoblasts are bone marrow stromal cells that contribute to the formation of stem cell niches and support normal hematopoiesis, leukemogenesis and development of metastases from distant cancers. This support is mediated through cell–cell contact, release of soluble mediators and formation of extracellular matrix. By using a proteomic approach, we characterized the protein release by in vitro cultured human MSCs (10 donors) and osteoblasts (nine donors). We identified 1379 molecules released by these cells, including 340 proteins belonging to the GO-term Extracellular matrix. Both cell types released a wide range of functionally heterogeneous proteins including extracellular matrix molecules (especially collagens), several enzymes and especially proteases, cytokines and soluble adhesion molecules, but also several intracellular molecules including chaperones, cytoplasmic mediators, histones and non-histone nuclear molecules. The levels of most proteins did not differ between MSCs and osteoblasts, but 82 proteins were more abundant for MSC (especially extracellular matrix proteins and proteases) and 36 proteins more abundant for osteoblasts. Finally, a large number of exosomal proteins were identified. To conclude, MSCs and osteoblasts show extracellular release of a wide range of functionally diverse proteins, including several extracellular matrix molecules known to support cancer progression (e.g., metastases from distant tumors, increased relapse risk for hematological malignancies), and the large number of identified exosomal proteins suggests that exocytosis is an important mechanism of protein release.

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THBS1 Is a Novel Serum Prognostic Factors of Acute Myeloid Leukemia

Cited by 27 publications

References 36 publications

New insight into long non-coding RNAs associated with bone metastasis of breast cancer based on an integrated analysis

New insight into long non-coding RNAs associated with bone metastasis of breast cancer based on an integrated analysis

A novel leukemic route of mutant NPM1 through nuclear import of the overexpressed long noncoding RNA LONA

The Extracellular Bone Marrow Microenvironment—A Proteomic Comparison of Constitutive Protein Release by In Vitro Cultured Osteoblasts and Mesenchymal Stem Cells

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