Blocking Oncostatin M receptor abrogates STAT3 mediated integrin signaling and overcomes chemoresistance in ovarian cancer.

Chemotherapy such as cisplatin is widely used to treat ovarian cancer either before or after surgical debulking. However, cancer relapse due to chemotherapy resistance is a major challenge in the treatment of ovarian cancer. The underlying mechanisms related to chemotherapy resistance remain largely unclear.

Optimized proximity ligation assay (PLA) for detection of RNA-protein complex interactions in cell lines.

Conventional proximity ligation assay (PLA) suffers from target specificity issues that curtail their accuracy on interpreting proximal interactions in cell biology. Here, we present a reliable and sensitive approach by including a fluorochrome-labeled mRNA fragment along with biotin-labeled RNA probe and a target-specific antibody, which were used to generate proximal ligation signals through linear connectors in intact cells. This protocol will be particularly useful for studying the proximal interactions between RNA binding proteins (RBPs) and their target mRNAs in cells.

Tumor Derived Extracellular Vesicles Drive T Cell Exhaustion in Tumor Microenvironment through Sphingosine Mediated Signaling and Impacting Immunotherapy Outcomes in Ovarian Cancer.

SPHK1 (sphingosine kinase-1) catalyzes the phosphorylation of sphingosine to sphingosine-1-phosphate (S1P), is found to be highly expressed in solid tumors. Here, extracellular vesicles (EVs) are identified as the key transporters of SPHK1 to the tumor microenvironment. Consequently, SPHK1-packaged EVs elevate S1P levels in the tumor microenvironment, where S1P appears as an immunosuppressive agent.

Patient-Derived Ovarian Cancer Spheroids Rely on PI3K-AKT Signaling Addiction for Cancer Stemness and Chemoresistance.

Ovarian cancer is the most lethal gynecological malignancy among women worldwide and is characterized by aggressiveness, cancer stemness, and frequent relapse due to resistance to platinum-based therapy. Ovarian cancer cells metastasize through ascites fluid as 3D spheroids which are more resistant to apoptosis and chemotherapeutic agents. However, the precise mechanism as an oncogenic addiction that makes 3D spheroids resistant to apoptosis and chemotherapeutic agents is not understood.

Tim-1 Deficiency Aggravates High-Fat Diet-Induced Steatohepatitis in Mice.

Non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) is commonly associated with obesity and characterized by excessive lipid accumulation and liver inflammation. The T cell immunoglobulin and mucin domain 1 (Tim-1), also known as hepatitis A virus cellular receptor 1 (Havcr-1) and kidney injury molecule 1 (Kim-1), has been shown to affect innate immunity-driven proinflammatory cascade in liver ischemia-reperfusion injury. However, its contribution to obesity-related NAFLD/NASH remains unknown.

Genetic Manipulation of Sirtuin 3 Causes Alterations of Key Metabolic Regulators in Melanoma.

The mitochondrial sirtuin SIRT3 plays key roles in cellular metabolism and energy production, which makes it an obvious target for the management of cancer, including melanoma. Previously, we have demonstrated that SIRT3 was constitutively upregulated in human melanoma and its inhibition resulted in anti-proliferative effects in human melanoma cells and in human melanoma xenografts. In this study, we expanded our data employing knockdown and overexpression strategies in cell culture and mouse xenografts to further validate and establish the pro-proliferative function of SIRT3 in melanocytic cells, and its associated potential mechanisms, especially focusing on the metabolic regulation.

Peritoneal Spread of Ovarian Cancer Harbors Therapeutic Vulnerabilities Regulated by FOXM1 and EGFR/ERBB2 Signaling.

Peritoneal spread is the primary mechanism of metastasis of ovarian cancer, and survival of ovarian cancer cells in the peritoneal cavity as nonadherent spheroids and their adherence to the mesothelium of distant organs lead to cancer progression, metastasis, and mortality. However, the mechanisms that govern this metastatic process in ovarian cancer cells remain poorly understood. In this study, we cultured ovarian cancer cell lines in adherent and nonadherent conditions and analyzed changes in mRNA and protein levels to identify mechanisms of tumor cell survival and proliferation in adherent and nonadherent cells.

ERBB3-induced furin promotes the progression and metastasis of ovarian cancer via the IGF1R/STAT3 signaling axis.

High-grade serous carcinoma, accounts for up to 70% of all ovarian cases. Furin, a proprotein convertase, is highly expressed in high-grade serous carcinoma of ovarian cancer patients, and its expression is even higher in tumor omentum than in normal omentum, the preferred site of ovarian cancer metastasis. The proteolytic actions of this cellular endoprotease help the maturation of several important precursors of protein substrates and its levels increase the risk of several cancer.

miRNA551b-3p Activates an Oncostatin Signaling Module for the Progression of Triple-Negative Breast Cancer.

Genomic amplification of 3q26.2 locus leads to the increased expression of microRNA 551b-3p (miR551b-3p) in triple-negative breast cancer (TNBC). Our results demonstrate that miR551b-3p translocates to the nucleus with the aid of importin-8 (IPO8) and activates STAT3 transcription.

Correction to: Inhibitory effects of tea polyphenols by targeting cyclooxygenase-2 through regulation of nuclear factor kappa B, Akt and p53 in rat mammary tumors.

The authors regret to inform that there were unknowing errors in figures. The corrected images are given below. These figures are not affecting the results and conclusion of the manuscript.

Kidney Injury Molecule-1 Is Upregulated in Renal Lipotoxicity and Mediates Palmitate-Induced Tubular Cell Injury and Inflammatory Response.

Diabetic nephropathy is increasingly recognized as a major contributor to kidney failure in patients with obesity and type 2 diabetes. This study was designed to identify the molecular mediators of kidney injury associated with metabolic syndrome with or without hyperglycemia. We compared renal gene expression profiles in Zucker lean (ZL), Zucker obese (ZO), and Zucker diabetic (ZD) rats using cDNA microarray with quantitative verification of selected transcripts by real-time PCR.

4'-Bromo-resveratrol, a dual Sirtuin-1 and Sirtuin-3 inhibitor, inhibits melanoma cell growth through mitochondrial metabolic reprogramming.

Sirtuin-1 and -3 (SIRT1 and SIRT3) are important nicotinamide adenine dinucleotide (NAD )-dependent deacetylases known to regulate a variety of cellular functions. Studies have shown that SIRT1 and SIRT3 were overexpressed in human melanoma cells and tissues and their inhibition resulted in a significant antiproliferative response in human melanoma cells and antitumor response in a mouse xenograft model of melanoma. In this study, we determined the antiproliferative efficacy of a newly identified dual small molecule inhibitor of SIRT1 and SIRT3, 4'-bromo-resveratrol (4'-BR), in human melanoma cell lines (G361, SK-MEL-28, and SK-MEL-2).

Saturated fatty acid stimulates production of extracellular vesicles by renal tubular epithelial cells.

Lipotoxicity, an accumulation of intracellular lipid metabolites, has been proposed as an important pathogenic mechanism contributing to kidney dysfunction in the context of metabolic disease. Palmitic acid, a predominant lipid derivative, can cause lipoapoptosis and the release of inflammatory extracellular vesicles (EVs) in hepatocytes, but the effect of lipids on EV production in chronic kidney disease remains vaguely explored. This study was aimed to investigate whether palmitic acid would stimulate EV release from renal proximal tubular epithelial cells.

Albumin induces CD44 expression in glomerular parietal epithelial cells by activating extracellular signal-regulated kinase 1/2 pathway.

De novo expression of CD44 in glomerular parietal epithelial cells (PECs) leads to a prosclerotic and migratory PEC phenotype in glomerulosclerosis. However, the regulatory mechanisms underlying CD44 expression by activated PECs remain largely unknown. This study was performed to examine the mediators responsible for CD44 induction in glomerular PECs in association with diabetes.

Saturated fatty acids bound to albumin enhance osteopontin expression and cleavage in renal proximal tubular cells.

Osteopontin (OPN) is one of the proinflammatory cytokines upregulated in the kidneys of diabetic animals and patients with nephropathy. An increase in urinary albumin and albumin-bound fatty acids (FA) presents a proinflammatory environment to the proximal tubules in proteinuric kidney diseases including diabetic nephropathy. This study was designed to examine if FA overload could stimulate OPN expression and cleavage in renal tubule epithelial cells.

Endocytosis of Albumin Induces Matrix Metalloproteinase-9 by Activating the ERK Signaling Pathway in Renal Tubule Epithelial Cells.

Matrix metalloproteinase-9 (MMP-9) is dysregulated in chronic kidney diseases including diabetic nephropathy. This study was performed to examine the expression of MMP-9 in renal tubule epithelial cells (TECs) under diabetic conditions and its regulatory mechanisms. We characterized MMP-9 protein in diabetic animals and primary cultured rat TECs exposed to exogenous albumin and high glucose.