Volume 102 Issue 5, May 2022
Inside the USCAP Journals
Recent progress on the biological functions of exosome-derived noncoding RNAs (exo-ncRNAs) in liver diseases is discussed in this review. Exo-ncRNAs are involved in the initiation and progression of liver diseases by regulating hepatic lipid metabolism, internal immunity, viral infection, fibrosis, biliary atresia and cancer. Exo-ncRNAs have clinical implications as promising biomarkers and therapeutic targets, especially for non-invasive diagnosis.
SIRT6 regulates SREBP1c-induced glucolipid metabolism in liver and pancreas via the AMPKα-mTORC1 pathway
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.
MiR-200c-3p targets SESN1 and represses the IL-6/AKT loop to prevent cholangiocyte activation and cholestatic liver fibrosis
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.
LncRNA MAPKAPK5_AS1 facilitates cell proliferation in hepatitis B virus -related hepatocellular carcinoma
The present study reveals that the hepatitis-B (HBV) antigen HBeAg found in HBV+HCC upregulates long non-coding RNA MAPKAPK5_AS1 (MAAS) expression in M2 macrophages by affecting its m6A modification. MAAS is transferred to HBV+HCC cells via exosomes, which in turn facilitates their proliferation. This is a novel role for MAAS and further elucidates the mechanism of HBeAg-induced HBV-related HCC development.
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.
The MFF-SIRT1/3 axis, regulated by miR-340-5p, restores mitochondrial homeostasis of hypoxia-induced pulmonary artery smooth muscle cells
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.
Ubiquitin-specific protease 35 (USP35) mediates cisplatin-induced apoptosis by stabilizing BIRC3 in non-small cell lung cancer
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.
Interactions between leucines within the signal peptides of megalin and stanniocalcin-1 are crucial for regulation of mitochondrial metabolism
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.
Conventional histological and cytological staining with simultaneous immunohistochemistry enabled by invisible chromogens
Conventional histological and cytological stains, including hematoxylin & eosin and Papanicolaou, are combined with immunohistochemistry and simultaneously evaluated on the same specimen slide by use of invisible chromogens. Visible and invisible light used to illuminate the specimen are separated and directed to color and monochrome cameras, respectively, providing conventional stain and immunohistochemistry in side-by-side videos on the computer monitor. Alternatively, multispectral imaging of single microscope fields provides archiving and further evaluation utilizing image processing.
A generative adversarial approach to facilitate archival-quality histopathologic diagnoses from frozen tissue sections
The authors synthesized formalin-fixed paraffin-embedded (FFPE)-like images (“virtual FFPE”) from frozen (FF) section samples. Five board-certified pathologists evaluated the results in a blinded test. Clinical assessments of disease on the virtual FFPE images showed a higher inter-observer agreement compared to FF images. These findings suggest that virtual FFPE images can increase the quality and speed of histopathologic examinations without adding to cost or effort.
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 (PKD1insG/+) 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 PKD1insG/+ pigs recapitulate the characteristic symptoms of ADPKD.