Articles in 2019

The authors present a rare case of intracranial solitary fibrous tumors/hemangiopericytomas (SFT/HPC) with intraspinal metastasis. A DSTYK mutation (Met296Ile) was identified as a potential driver of intraspinal metastasis. This DSTYK mutation promotes cell migration and invasion of SFT/HPC cells via activation of ERK1/2/MMP2/9 signaling, which may provide new biological insights for SFT/HPC study.

In this work, the authors propose a new framework based on deep-learning to comprehensively assess the microvascular condition of the glioma patients by automated analysis of the H&E stained whole slide images. They show that microvascularity has a tight relationship with the diagnosis of glioma and can be used as an important prognostic indicator.

The authors report a previously unappreciated miR-26a-mediated regulatory model in which miR-26a promotes invasion/metastasis by inhibiting the phosphatase PTEN and inhibits cell proliferation by repressing the methyltransferase EZH2 in hepatocellular carcinoma. Although therapeutic miR-26a delivery significantly suppresses tumorigenesis in mice, further studies are warranted before it is a relevant as a target for HCC therapy.

The biologic features of diffuse large B-cell lymphoma (DLBCL) with PD-L1 expression remains unknown. This study demonstrates that DLBCL with PD-L1 expression features an activated B-cell receptor signal pathway, and that inhibiting BCR and blocking PD-L1 expression may synergize to target DLBCL.

This paper examines whether the nuclear E3 ubiquitin ligase MDM2 and/or the cyclin-dependent kinase CDK4 produce well-differentiated liposarcoma (WDLPS)/dedifferentiated liposarcoma (DDLPS) using transformed human bone marrow stem cells through in vitro and in vivo functional experiments. The authors found that co-overexpression of MDM2 and CDK4 causes high-grade sarcoma with a dedifferentiated liposarcoma-like morphology.

RXRα phosphorylation-deficient mutant mice with the mutation Thr 167 to Ala exhibit altered regulation of metabolic pathway gene expression in white adipose tissue. This result, combined with data on muscle and liver gene expression, suggest that the RXRα Thr 167 phosphorylation signal coordinates these three organs for regulation of energy metabolism and maintenance of glucose homeostasis.

Trp53 null and R270H mutations had comparable effects on tumor phenotypes in a genetically engineered mouse model of colorectal cancer (CRC). The mouse tumors with Trp53 null or R270H mutations as well as human CRCs with null or codon R273 missense mutations had similar gene expression profiles. These findings raise questions about a general role for gain-of-function effects for mutant p53 proteins in CRC.

The authors employed a monoclonal antibody, 297-11A, to determine preferential display of sialyl 6′-sulfo N-acetyllactosamine-capped O-glycans on high endothelial venules (HEVs) in human peripheral lymph nodes. These glycans were also displayed on HEV-like vessels in tumor-infiltrating lymphocyte aggregates in various cancers. Thus, 297-11A-positive sulfated glycans likely function in physiologic and pathologic lymphocyte trafficking.

High-mobility group box 1 (HMGB1) is actively secreted from inflammatory cells and acts via a non-cell autonomous mechanism to mediating cell proliferation and migration. The authors sought to determine the role of HMGB1 in modulation of dopaminergic neurons. Their results suggest that an increase of HMGB1, released from astrocytes, upregulates TH expression in a Parkinsonian mouse model, thereby maintaining dopaminergic neuronal functions.

In this paper, the authors show that miR-135b-5p has prognostic value for ductal carcinoma in situ with microinvasion (DCIS-Mi). The inhibition of miR-135b-5p promotes cell proliferation, epithelial–mesenchymal transition, migration and invasion by targeting (SDCBP). The MiR-135b-5p/SDCBP axis is a crucial determinant of breast cancer metastasis at a very early stage.

Lack of expression of Tgf-β1 in the embryonic lung mesenchyme led to severe lung hypoplasia, increase of cell apoptosis and reduced lung branching morphogenesis. In the mutant lung, FGF10 signaling pathway was inhibited and the vascular system was underdeveloped. This genetic mouse model will be helpful to identify the key pathogenic mechanisms underlying lung hypoplasia in humans.

The authors established a bioinformatics approach to assessing the impact of melanoma mutants, among a set of extra-cellular matrix structural proteins, on the sensitivity of matrix metalloproteinase-2 (MMP2), extensively associated with melanoma. Results indicate that tumor samples with mutant amino acids adjacent to MMP2 sites also represented a better survival rate.

CD271, also known as nerve growth factor receptor, is expressed in lung, penile, vulvar, and esophageal squamous carcinoma, but not in lung adenocarcinoma. This study determined that cell proliferation in lung squamous cell carcinoma depends on CD271, suggesting that siRNA against CD271 is a potential therapeutic strategy for certain cancers.

The authors show that normal apoAI/HDL and an apoAI mimetic have protective effects on damaged podocytes in culture. In vivo, infusion of the apoAI mimetic lessens glomerular damage, proteinuria, and atherosclerosis. These findings suggest that supplemental apoAI/apoAI mimetic 4F may be novel interventions to lessen podocyte damage, and the resulting proteinuria and atherosclerosis.

RNA binding proteins associated with amyotrophic lateral sclerosis and muscle myopathy possess sequence elements that bear resemblance to yeast prion domains. Fusion proteins of the nuclear matrix protein matrin 3 (MATR3), transactive response DNA binding proteinTARDBP43 (TDP43) or the RNA binding protein FUS with yellow fluorescent protein or mCherry were used to examine phase separation and protein interaction in mouse C2C12 myoblast cells. The authors show that N-terminal sequences in MATR3 can mediate phase separation into intranuclear droplet-like structures, which recruit TDP43 variants lacking RNA binding elements.

The main ligands involved in lymphangiogenesis, VEGF-C and VEGF-D, are abundantly present in renal tubules at baseline and are secreted following injury with subsequent increase in serum and urinary levels. Lymphatic vessel formation is robustly induced following kidney injury and such induction is independent of the nature of insult and is a hallmark of kidney disease.

Both toll-like receptors and nucleotide-binding oligomerization domain (NOD)-like receptors induce an inflammatory response at risk of causing tissue damage. However, the cross-regulation between interleukin-1 (IL-1) receptors and NOD2 is not completely understood. The authors show that IL-1α/β increase NOD2-induced inflammatory response by enhancing muramyl dipeptide-induced activation of MAPK signaling pathways via ERK, JNK, and P38.

Pirfenidone prevents lipotoxicity-induced insulin resistance and steatohepatitis by regulating immune cell accumulation and macrophage polarization in the livers of mice. Additionally, pirfenidone suppresses hepatic fibrosis by inhibiting activation of stellate cells and TGF-β1 expression; and reverses insulin resistance, hepatic inflammation, and fibrosis in mice with pre-existing nonalcoholic steatohepatitis.

In order to find a therapeutic target for triple negative breast cancer (TNBC), the authors performed a siRNA screening and identified the cell cycle regulator polo-like kinase 1 (PLK) as an essential molecule for survival of TNBC cells. PLK1 is highly expressed in TNBC tissue and inhibition of PLK1 triggers apoptosis in a series of TNBC cell lines.

This paper defines the role of the protein autophagy-related 7 (Atg7) in triple-negative breast cancer (TNBC). Atg7 inhibits proliferation and migration, and promotes apoptosis of TNBC cells. Furthermore, Atg7 prevents epithelial-mesenchymal transition through downregulation of aerobic glycolysis. Atg7 is therefore a potential prognostic marker and therapeutic target for TNBC.