PDF file - 73K

PDF file - 204K, Microarray analysis of EMT-relevant genes in HHV-8-infected LNCaP-V219 cells cultured in androgen depleted (CSFBS) conditions.

PDF file - 118K, Temporal changes in EZH2, SUZ12 and the H3K27-me3 mark during sodium butyrate-induced reactivation of HHV-8.

<p>PDF file - 124K, Reactivation of HHV-8 from LNCaP-v219 cells relieves EZH2-mediated repression of DAB2IP and MSMB expression.</p>

<p>PDF file - 112K, Microarray analysis of altered genes in HHV-8-infected LNCaP-V219 cells cultured in androgen depleted (CSFBS) conditions.</p>

PDF file - 135K, Predicted outcomes of interactions between HHV-8 and components of the repressive Polycomb repressor complex (PRC2) during latency and upon viral reactivation.

PDF file - 149K, Long-term infection and reactivation of HHV-8 in DU145 cells.

PDF file - 121K, MSMB induces apoptosis in PC3 cells but reverses HHV-8-induced androgen-independent growth in LNCaP-v219 cells.

This is a case series of three patients in our hospital system who developed acquired thrombotic thrombocytopenic purpura (aTTP) after testing positive for COVID-19 infection. Two patients had acute COVID-19 infections, and one had COVID-19 IgG antibodies consistent with prior COVID-19 infection. Twelve additional cases of aTTP after COVID-19 infection were found in the literature. COVID-19 creates alterations in the vWF-ADAMTS-13 axis with reduced ADAMTS-13 in acute illness that may lead those patients who are predisposed into fulminant aTTP. Further genetic studies are necessary to uncover why some patients with COVID-19 can have concurrent aTTP. For those with a prior COVID-19 infection, molecular mimicry with autoantibodies to ADAMTS-13 is likely the predominant trigger, but having an underlying predisposition (prior episode of TTP, genetic predisposition to autoimmune conditions, or breast cancer history) creates an environment that could be a possible trigger for aTTP.

Hepatitis C virus (HCV) infection is a serious worldwide healthcare issue. Its association with various liver diseases including hepatocellular carcinoma (HCC) is well studied. However, the study on the relationship between HCV infection and the development of insulin resistance and diabetes is very limited. Current research has already elucidated some underlying mechanisms, especially on the regulation of metabolism and insulin signalling by viral proteins. More studies have emerged recently on the correlation between HCV infection-derived miRNAs and diabetes and insulin resistance. However, no studies have been carried out to directly address if these miRNAs, especially circulating miRNAs, have causal effects on the development of insulin resistance and diabetes. Here, we proposed a new perspective that circulating miRNAs can perform regulatory functions to modulate gene expression in peripheral tissues leading to insulin resistance and diabetes, rather than just a passive factor associated with these pathological processes. The detailed rationales were elaborated through comprehensive literature review and bioinformatic analyses. miR-122 was identified to be one of the most potential circulating miRNAs to cause insulin resistance. This result along with the idea about the driver function of circulating miRNAs will promote further investigations that eventually lead to the development of novel strategies to treat HCV infection-associated extrahepatic comorbidities.

Abstract Steroid hormone receptors such as estrogen and progesterone receptors are well studied in breast cancer pathology; they are also used as drug targets for breast cancer therapy in the clinic. In contrast, glucocorticoid (GC) as a ubiquitous stress activated steroid hormone is less investigated in breast cancer. However, GC is frequently used as a co-treatment for breast cancer chemotherapy that generates some controversial effects to even promote cancer progression or recurrence in certain subtypes of breast cancer. To address this clinical issue, we focused on investigating the specificity of GC signaling on breast cancer cell behaviors in this study. When breast cancer cells were treated by dexamethasone (Dex), they were more responsive to cell migration (measured by electric cell-substrate impedance sensing, ECIS) than the effects on cell proliferation and apoptosis, wherein MDA-231 (triple negative breast cancer) cell was more sensitive to Dex than MCF7 cell (luminal A subtype). Further gene expression analysis by qRT-PCR microarray revealed that the glucocorticoid receptor (GR) responsive gene patterns are different between these two subtypes of breast cancer cells. One of remarked changes was that Snai2 (a zinc finger transcriptional factor) was highly activated in both cell lines. Western blotting analysis confirmed that MDA-231 cells have much higher basal level of Snai2 but with less fold increase upon Dex treatment than MCF-7. GR response elements (GREs) were also identified in the promoter region of Snai2, thus confirming Snai2 as a new target gene of GR in breast cancer. When Snai2 was knocked out by CRISPR, it was found that the basal migration rate was decreased in both cell lines. More importantly, their response rates to Dex treatment were also decreased as compared to the wild type cells. These decreases in cell migration are similar to those treated by GR antagonist RU486, thus confirming that Snai2 is a mediator to regulate the effects of GC/GR signaling on breast cancer cell migration. In summary, this study identified Snai2 as a new target gene of GR to regulate cell migration and potentially metastasis in response to GC signaling. The differential regulation of different subtypes of breast cancer cells by GC signaling was also confirmed. (+ equal contribution; * Corresponding author). Citation Format: Jun Ling, Adit Singhal, Zenaida P. Lopez-Dee, Brittany Porreca, Trinity Sprague. Snai2 is a new target to mediate glucocorticoid signaling on breast cancer cell migration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 45.

Abstract Mechanisms underlying progression to androgen-independent prostate cancer following radical ablation therapy remain poorly defined. Although intraprostatic infections have been highlighted as potential cofactors, pathogen influences on pathways that support tumor regrowth are not known. To explore this provocative concept, we derived androgen-sensitive and -insensitive prostate epithelial cells persistently infected with human herpesvirus 8 (HHV-8), an oncogenic herpesvirus that has been detected in normal prostate epithelium, prostate adenocarcinoma, and biologic fluids of patients with prostate cancer, to explore its effects on transition to hormone-refractory disease. Strikingly, we found that HHV-8 infection of androgen-sensitive prostate cancer cells conferred the capacity for androgen-independent growth. This effect was associated with altered expression and transcriptional activity of the androgen receptor (AR). However, HHV-8 infection bypassed AR signaling by promoting enhancer of zeste homolog 2 (EZH2)–mediated epigenetic silencing of tumor-suppressor genes, including MSMB and DAB2IP that are often inactivated in advanced disease. Furthermore, we found that HHV-8 triggered epithelial-to-mesenchymal transition. Although HHV-8 has not been linked etiologically to prostate cancer, virologic outcomes revealed by our study provide mechanistic insight into how intraprostatic infections could constitute risk for progression to androgen-independent metastatic disease where EZH2 has been implicated. Taken together, our findings prompt further evaluations of the relationship between HHV-8 infections and risk of advanced prostate cancer. Cancer Res; 73(18); 5695–708. ©2013 AACR.