Articles

SLUG is expressed in the myoepithelial cells of normal salivary glands and is highly upregulated in the neoplastic myoepithelial cells and stromal cells of pleomorphic adenoma (PA). SLUG is less likely to be affected by PLAG1. SLUG is involved in the regulation of epithelial-mesenchymal transition (EMT) marker expression in primary cultured PA cells, indicating that SLUG might be a key transcription factor controlling EMT in PA.

A convolutional neural network (U-Net) for the assessment of aberrant CTLA-4 antibody staining using two independent antibody clones (MSVA-152R and CAL49) was trained and validated on 4582 tumor samples in this study. The deep learning-based framework facilitated automated CTLA-4 quantification in more than 90 different tumor entities via compensating for individual antibody shortcomings.

LncRNA ROR knockdown inhibits cardiomyocyte pyroptosis and inflammation induced by ischemia/reperfusion (I/R), while miR-185-5p knockdown accelerates the effect. ROR promotes CDK6 expression by targeting miR-185-5p. ROR promotes cardiomyocyte damage and pyroptosis by increasing CDK6 expression via miR-185-5p, suggesting that ROR may be a new therapeutic target of myocardial I/R injury.

Megalin shuttles hormones (stanniocalcin-1, angiotensin II, TGF-β) from the cell surface to the mitochondria through retrograde early endosomes to Golgi- and Rab32-mediated pathway (PMID: 29916093). Here we show STC1-FLAG expressed in megalin KO cells does not reach the mitochondria; thus, mitochondrial STC1 is extracellularly-derived. Leucines within the signal peptides of megalin and STC1 mediate their interaction; mutations of these leucines and interference with STC1-megalin binding diminishes mitochondrial respiration and glycolysis.

The imbalance between the proliferation and apoptosis of pulmonary arterial smooth muscle cells (PASMCs) is an important pathological process in pulmonary arterial hypertension (PAH). Mitochondrial dynamics and quality control play important roles in maintaining the cell proliferation–apoptosis balance. This paper reveals that miR-340-5p upregulates SIRT1/3 by targeting MFF, therefore improving mitochondrial dysfunction to maintain the proliferation–apoptosis balance of hypoxia-treated PAMSCs.

The authors demonstrate that the expression of SOCS-7 is decreased in (HCC) cells, as well as in patients, and overexpression of SOCS-7 significantly decreases the proliferation and migration of HCC cells and increases apoptosis in cultured HCC cells. An animal xenogeneic model shows that overexpression of SOCS-7 inhibits tumors, and knockout of SOCS-7 results in tumor growth.

The authors successfully developed two novel murine models for high-fat diet-induced nonalcoholic steatohepatitis that progresses to hepatic tumors with proliferative changes similar to those seen in humans. The jvs/+ mice with low carnitine as well as wild-type mice with early-stage impaired glucose tolerance induction by alloxan treatment developed obesity, insulin resistance, steatohepatitis and fibrosis, and eventually enhanced tumorigenesis. These results indicate that low carnitine and impaired glucose tolerance are important factors for the progression of nonalcoholic steatohepatitis.

The authors illustrate that ubiquitin-specific protease 35 (USP35) alleviates cisplatin-induced cell apoptosis by directly interacting with and stabilizing BIRC3. A significant positive correlation was observed between USP35 and BIRC3 in human NSCLC tissues. They hypothesize that USP35 plays a vital role in resistance to cisplatin-induced cell death through the overexpression of BIRC3, and might be a potentially novel therapeutic target in human NSCLC.

There is a lack of blood biomarkers to diagnose glioblastoma (GBM) patients. This retrospective pilot study aims to determine cell-free microRNAs (cfmiRs) in plasma samples from primary and recurrent GBM patients. Thus, 142 plasma and tissue samples were analyzed using the HTG miRNA whole transcriptome assay (WTA). By combining bioinformatic analysis and receiver operating characteristic curves, we showed that cfmiR-3180-3p and cfmiR-5739 have potential utility in primary and recurrent GBM diagnosis.

This study highlights a novel therapeutic target for glioma. Long noncoding RNA highly upregulated in liver cancer (HULC) stabilizes forkhead box M1 (FOXM1) to upregulate the expression of anterior gradient 2 (AGR2) and hypoxia-inducible factor-1α (HIF-1α), thereby promoting glycolysis and stemness of glioma stem cells and eventually accelerating the development of glioma.

The authors demonstrate that carnitine palmitoyltransferase 1A (CPT1A) expression is reduced in glioma stem cells (GSCs) in comparison with non-stem tumor cells. CPT1A overexpression promotes mitochondrial fusion and GSC differentiation by increasing the phosphorylation of dynamin-related protein 1 (Drp1) at Ser-637, thus impairing GSC-derived xenograft growth and prolonging survival in tumor-bearing mice. These results suggest that CPT1A could be a molecular target for GSC differentiation therapy.

Commensal microbe effects on alveolar bone homeostasis have been attributed to the oral microbiota, yet the impact of commensal gut microbes is unknown. Studies performed with segmented filamentous bacteria (SFB) monoassociated mice revealed commensal gut microbes modulate osteoimmune responses and skeletal homeostasis in alveolar bone. This work challenges the current paradigm that alveolar bone health is strictly regulated by oral microbes.

This study reveals a novel role for the stress-response protein sirtuin 6 (SIRT6) in modulation of glucolipid metabolism disorders in the liver and pancreas under conditions of overnutrution and starvation. The authors show that SIRT6 regulates SREBP1c through the AMPKα-mTORC1 pathway, which and then affects glucolipid metabolic enzymes in an LXR-independent pathway.

Osteosarcoma is a tumour with a highly complex genome, which hampers the identification of driver genes. Using a model of murine mesenchymal stem cells (MSCs) with deficient p15^Ink4b, p16^Ink4a, or p19^Arf that transform earlier compared to wild-type MSCs, the authors demonstrated that loss of p16^Ink4a is a driver of osteosarcomagenesis. This can be exploited with a CDK4/CDK6 inhibitor, as osteosarcoma cells showed sensitivity to palbociclib which might be used as a novel therapeutic option.

Under high-glucose conditions, LECs obtain characteristics of mesenchymal cells such as high migratory capacity and invasiveness, which is the foundational basis for DC progression. The authors demonstrated that lncRNA GAS5 facilitates high glucose-induced lens epithelial cell migration and epithelial-to-mesenchymal transition by regulating the miR-204-3p/TGFBR1 axis. This study, therefore, provides novel insights into the pathogenesis of DCs.

The smoothened (SMO) receptor maintains levels of insulin-like growth factor 1 receptor (IGF1R) in several types of cancer cells, and high protein levels of both receptors correlate with poor survival in diffuse large B-cell lymphoma (DLBCL) patients. Loss of SMO favors IGF1R degradation over recycling, and IGF1R-mediated AKT/PI3K signaling, but MAPK is not significantly impaired. The preferential disruption of AKT signaling correlates with a loss of IGF1R and AKT in raft microdomains.

Cholangiocytes are the primary targets of cholangiopathies. This study elucidates the role of miR-200c in maintaining cholangiocyte homeostasis making use of cell culture and mouse models of cholestasis. MiR-200c restrains the proliferative and neuroendocrine-like activation of cholangiocytes by targeting sestrin 1(SESN1) and inhibiting the IL-6/AKT feedback loop to prevent cholestatic liver injury. The findings provide critical mechanistic insights into biliary liver fibrosis and suggest miR-200c may be a novel therapeutic target of cholangiopathies.

Thioredoxin domain containing 5 (TXNDC5) is highly expressed in patients with septic shock. It is also upregulated in mice with lipopolysaccharide (LPS)-induced sepsis and mouse macrophages subjected to LPS stimulation. Txndc5 depletion reduced inflammatory cytokine production and affected recruitment of macrophages and neutrophils in LPS-challenged mice. TXNDC5 inhibition alleviated LPS-induced sepsis by inhibiting the nuclear factor kappa B signaling pathway. These findings suggest that TXNDC5 inhibition may be a therapeutic approach for sepsis.