Research articles

Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic skin disease caused by mutations in the gene COL7A1. The authors developed a strategy to investigate the impact of each pathogenic mutation on skin integrity using CRISPR-mediated genome editing in mice in order to create a reliable animal model for the study of this devastating disease.

The authors show that LINC01963 is overexpressed in the PC3-DR cells and that LINC01963 silencing enhances the chemosensitivity of PC3-DR to docetaxel and inhibits tumorigenicity and lung metastasis. Silencing of LINC01963 ireduces TrkB protein levels to enhance the chemosensitivity of cells to docetaxel by competitively binding to miR-216b-5p.

The authors defined the role of DNA methyltransferase 1 (DNMT1) during heart failure and identified the underlying mechanism. DNMT1 enhances the methylation of the miR-152-3p promoter region. DNMT1 also enhances the expression of the transcription factor ETS1, which further elevates RhoH expression. DNMT1 therefore induces heart failure by inhibiting mitophagy of in H9c2 cells through regulating the miR-152-3p/ETS1/RhoH axis.

Mammals exhibit epidermal patterning, as seen in mouse tail scales and human skin microtopography. In this article, the authors demonstrate that type XVII collagen (COL17), a niche for epidermal stem cells, modulate epidermal patterning in mice and humans. COL17 further prevents wound-induced epidermal deformation. This study paves the way for elucidating the role of the stem cell niche in tissue pattern formation.

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.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the formation of cysts within the kidneys. The authors generated PKD1 heterozygous knockout (PKD1^insG/+) pigs by CRISPR-Cas9 and somatic cell cloning techniques. The founder cloned animals and progeny showed the renal cyst formation from the neonatal stage, interstitial fibrosis of the renal tissue, and the presence of a premature asymptomatic stage. Their findings demonstrate that PKD1^insG/+ pigs recapitulate the characteristic symptoms of ADPKD.