Articles in 2020

This study confirms that the expression of GTSE1 in prostate cancer is significantly increased and negatively correlated with patient prognosis. Furthermore, GTSE1 promotes prostate cancer cell proliferation via the SP1/FOXM1 signaling pathway, which facilitates tumorigenesis and progression. These results suggest that GTSE1 has potential value as a prognostic marker and therapeutic target in prostate cancer.

This study reveals that upregulation of lncRNA small nucleolar RNA host gene 5 (SNHG5), mediated by Yin Yang 1 (YY1), activates connective tissue growth factor (CTGF)/vascular endothelial growth factor (VEGFA) axis via targeting miR-26b to regulate angiogenesis of acute myelogenous leukemia (AML), providing new insights into mechanisms of AML.

This paper reports the optimisation of digital pathology approaches for evaluating drug responses in patient-derived explants at endpoint. The authors compare three image analysis software platforms and find that all three generate comparable data to that of a histomorphometrist. They also demonstrate the power of multi-immunofluorescence staining for monitoring multiple biomarkers simultaneously compared to virtual double staining of sequential sections by immunohistochemistry.

The authors show that plasminogen activator inhibitor-1 (PAI-1) derived from cancer-associated fibroblasts promotes the invasion of esophageal squamous cell carcinoma (ESCC) cells and the migration of macrophages via lipoprotein receptor-related protein 1 (LRP1). High expression of PAI-1 and/or LRP1 is associated with poor prognosis in patients with ESCC, and the PAI-1/LRP1 axis could be a target of anticancer therapy.

The correlation between SMAD4 mutations and clinico-molecular features in a Chinese non-small cell lung cancer (NSCLC) cohort was studied using next-generation sequencing. Integrated bioinformatics analyses based on public databases were conducted to further investigate the prognostic value of SMAD4. Results showed that SMAD4 alteration was associated with poor survival and resistance to platinum-based chemotherapy, suggesting that SMAD4 alteration might be a predictive marker in NSCLC.

Vascular endothelial growth factor secreted by placenta-derived mesenchymal stem cells (PD-MSCs) promotes follicular development and ovarian function after ovariectomy through vascular remodeling. These results provide fundamental data for understanding the therapeutic mechanisms of stem cell therapy based on placenta-derived mesenchymal stem cells PD-MSCs and provide a theoretical foundation for their application for obstetrical and gynecological diseases, including infertility and menopause.

Chronic stress can change hepatic lipid accumulation via elevation of hepatic β-muricholic acid levels in nonalcoholic steatohepatitis mice, disrupting bile acid homeostasis by induction of hepatic Cyp7a1 expression. This study describes a new role βMCA in the liver, indicating its potential usefulness for nonalcohol fatty liver disease therapy.

This study demonstrates that ATF-3 plays a suppressive function in melanoma tumor progression via a significant decrease in expression in metastatic melanoma and correlation with tumor virulence. ATF-3 overexpression significantly inhibits cell growth, migration, and invasion in vitro, and abrogates tumor growth in a human melanoma xenograft mouse model in vivo.

This study shows that exercise increases adropin levels and inhibits NLRP3 inflammasome activation in mice with diet-induced nonalcoholic steatohepatitis (NASH). Furthermore, adropin suppresses palmitic acid-induced NLRP3 inflammasome activation in hepatocytes and Kupffer cells. These results indicate that exercise may inhibit NLRP3 inflammasome activation via adropin induction, resulting in NASH improvement.

Nitric oxide (NO) plays an important role in tumor biology, including the generation and maintenance of cancer stem cells (CSCs) subpopulations. Here the authors show that the inhibition of NO production in estrogen-positive breast cancer not only impact the CSC subpopulation but also enhance the efficacy of hormonal therapy with tamoxifen.

Abnormal expression of myocardial infarction-related transcription factor 2 (Mirt2) is associated with myocardial infarction, cardiomyocyte apoptosis and oxidative stress in rats with acute myocardial infarction (AMI). These effects involve the miR-764/PDK1/AKT axis. Therefore, the current findings provide a theoretical basis for the diagnosis and treatment of clinical myocardial infarction by monitoring changes in Mirt2 levels.

An increase in podocyte apoptosis is positively correlated with the cytoplasmic distribution of YAP in focal segmental glomerulosclerosis (FSGS). YAP inhibition by verteporfin induces nuclear exclusion of YAP, thus increasing the podocyte apoptosis and accelerating disease progression. Therefore, this study suggests that YAP activation and nuclear distribution in podocytes is an endogenous anti-apoptotic mechanism during the progression of FSGS.

Injury-induced transforming growth factor β1 increases sphingosine 1-phosphate (S1P) generation by upregulating in sphingosine kinase 1 activity. The high levels of S1P formation stimulate the S1PR3-linked signaling pathway, which in turn increases vascular endothelial growth factor-A expression levels and angiogenesis in mouse corneas.

SECISBP2 overexpression is an independent negative prognostic predictor in diffuse large B-cell lymphoma. Additionally, SECISBP2 positively correlates with selenoprotein expression. In vitro, SECISBP2 knockout increases intracellular reactive oxygen species accumulation via the downregulation of selenoproteins, inhibiting cell growth and promoting cell death after doxorubicin treatment. Therefore, SECISBP2 is a potential therapeutic target for malignant lymphoma.

The authors show that genomes of female infertility patients harbor mutations within miRNA genes and 3’ UTR miRNA binding sites that are likely to affect maternal transcript clearance. Such disruption may not be compatible with zygotic genome activation and could cause a failure in embryonic development, implantation or cause early miscarriage, resulting in an infertility diagnosis.

The authors report the feasibility of generating, expanding, and enumerating viable patient-derived intraductal papillary mucinous neoplasm (IPMN) tumor and normal pancreatic organoids from fresh and cryopreserved resected tissue. Organoids were characterized histologically and genomically and recapitulated the morphological and mutational profiles of resected IPMNs, suggesting promise of organoids for translational efforts.

In this study, the authors provide evidence that ectopic expression of oncogenic mutant Kras in pancreatic ducts generates early and late (PanIN) and pancreatic ductal adenocarcinoma (PDAC) . They characterized this Ras rheostat model which reveals elevated Kras mutation frequency and loss of PTEN are important drivers of PanIN and invasive ductal derived PDAC.

In this study, effect of Osr1 deficiency in promoting non-alcoholic fatty liver disease progression was examined. The authors demonstrate that Osr1 regulates hepatic inflammation and cell survival through multiple signaling pathways and DNA methylation modification.

The authors investigated the clinicopathologic significance of microRNA-130b expression and analyzed its cancer-specific functions using a cancer cell line. High microRNA-130b expression was associated with adverse clinicopathologic parameters and poor patient outcomes. In vitro, downregulation of microRNA-130b caused a decrease in cell proliferation, migration, and invasion. Hence, miR-130b is a potential therapeutic target for lung cancer.

C-X-C chemokine receptor type 5 (CXCR5) regulates retinal pigment epithelium (RPE) homeostasis through PI3K/AKT signaling and by suppression of FOXO1 activation. CXCR5-deficency leads to decreased RPE differentiation, compromised barrier function, and increase in epithelial-mesenchymal transition markers (αSMA, N-cadherin, and vimentin) in CXCR5-deficient RPE cells in vitro and in CXCR5^−/− mice.