Upregulation of Breast Cancer Resistance Protein Expression was Decreased in Plasma Membrane of Colon Cancer with Metastasis of Lymphatic Node.

BACKGROUND: ATP-binding cassette sub-family G member 2 (ABCG2), an ABC transport protein involved in the efflux of anticancer compounds, has been reported to have altered expression levels in several cancers including breast, colon, and gastric cancer, etc. However, its expression change (up- or down-regulated in cancer) is still contradictory. METHODS: We performed immunohistochemistry to examine ABCG2 expression in the microarray with 90 pairs of colon cancer and their adjacent normal tissues. To find the expression of ABCG2 in lymphatic node metastasis (N1) and N0, we performed immunofluorescence, analyzed by Confocal technology. RESULTS: Compared to adjacent normal tissues, the percentage and density of positive cells expressing ABCG2 in colon cancer were significantly increased. In addition, ABCG2 expression in plasma membrane was related to lymph node metastasis in colon cancer, which was further verified to be downregulated by 2.7-fold in N1 to N0 through immunofluorescent analysis. CONCLUSIONS: ABCG2 expression in colon cancer was up-regulated, and its expression was decreased in the plasma membrane of colon cancer with lymphatic node metastasis (N metastasis).

Zika virus infects renal proximal tubular epithelial cells with prolonged persistency and cytopathic effects.

Zika virus (ZIKV) infection can cause fetal developmental abnormalities and Guillain-Barré syndrome in adults. Although progress has been made in understanding the link between ZIKV infection and microcephaly, the pathology of ZIKV, particularly the viral reservoirs in human, remains poorly understood. Several studies have shown that compared to serum samples, patients' urine samples often have a longer duration of ZIKV persistency and higher viral load. This finding suggests that an independent viral reservoir may exist in the human urinary system. Despite the clinical observations, the host cells of ZIKV in the human urinary system are poorly characterized. In this study, we demonstrate that ZIKV can infect renal proximal tubular epithelial cells (RPTEpiCs) in immunodeficient mice in vivo and in both immortalized and primary human renal proximal tubular epithelial cells (hRPTEpiCs) in vitro. Importantly, ZIKV infection in mouse kidneys caused caspase-3-mediated apoptosis of renal cells. Similarly, in vitro infection of immortalized and primary hRPTEpiCs resulted in notable cytopathic effects. Consistent with the clinical observations, we found that ZIKV infection can persist with prolonged duration in hRPTEpiCs. RNA-Seq analyses of infected hRPTEpiCs revealed a large number of transcriptional changes in response to ZIKV infection, including type I interferon signaling genes and anti-viral response genes. Our results suggest that hRPTEpiCs are a potential reservoir of ZIKV in the human urinary system, providing a possible explanation for the prolonged persistency of ZIKV in patients' urine.

Suppressor of cytokine signaling (SOCS)5 ameliorates influenza infection via inhibition of EGFR signaling.

Influenza virus infections have a significant impact on global human health. Individuals with suppressed immunity, or suffering from chronic inflammatory conditions such as COPD, are particularly susceptible to influenza. Here we show that suppressor of cytokine signaling (SOCS) five has a pivotal role in restricting influenza A virus in the airway epithelium, through the regulation of epidermal growth factor receptor (EGFR). Socs5-deficient mice exhibit heightened disease severity, with increased viral titres and weight loss. Socs5 levels were differentially regulated in response to distinct influenza viruses (H1N1, H3N2, H5N1 and H11N9) and were reduced in primary epithelial cells from COPD patients, again correlating with increased susceptibility to influenza. Importantly, restoration of SOCS5 levels restricted influenza virus infection, suggesting that manipulating SOCS5 expression and/or SOCS5 targets might be a novel therapeutic approach to influenza.