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MicroRNAs play a critical role in chemoresistance and are implicated in various biological and pathological processes of cells. The objective of the present study was to explore the role of miR-133b and its mechanism in the regulation of cisplatin resistance and tumor progression in cisplatin-resistant non-small cell lung cancer (NSCLC) cells. Reverse transcription-quantitative polymerase chain reaction and western blot assays of the cisplatin-resistant cell lines A549/DPP and H1299/DDP displayed the reduced expression of miR-133b and increased expression of glutathione-S-transferase P1 (GSTP1) in the resistant cells compared with the respective parental cell lines A549 and H1299. Cell Counting kit-8, flow cytometry, colony formation and Transwell migration assays indicated that the overexpression of miR-133b increased the chemosensitivity to cisplatin and attenuated the proliferation and migration capacities of the cisplatin-resistant NSCLC cell lines in vitro. A dual-luciferase reporter assay demonstrated that miR-133b negatively regulated the expression of GSTP1 by targeting its 3′-untranslated region. In addition, the knockdown of GSTP1 by transfection with small interfering RNA exerted similar effects on cell chemosensitivity, proliferation and migration as did ectopic miR-133b expression, in addition to the upregulation of Bax and down-regulation of Bcl-2, survivin and matrix metalloproteinase expression. In conclusion, the present study findings provide the insights that miR-133b reduces cisplatin resistance and its overexpression contributes to the suppression of the malignant growth and aggressiveness of cisplatin-resistant NSCLC cells by targeting GSTP1. This could potentially be exploited as a novel therapeutic strategy for the reversal of cisplatin resistance.

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Purpose To research the distribution and quantitative changes of UT-A1, UT-B1, and AQP5 in uremic skin tissue. Methods 34 cases of uremic patients (UP) and 11 controls were recruited. Immunohistochemistry, immunofluorescence, RT-PCR, and Western Blot were used to identify the proteins in sweat glands. Results AQP5, UT-A1, and UT-B1 were expressed and localized in human skin basal lines, skin sweat glands, and sweat ducts, both in UP and controls. Compared to controls, AQP5 mRNA abundance was significantly decreased in UP (P < 0.01), and, with the decrease of eGFR, the AQP5 expression was significantly decreased (P < 0.05). By contrast, UT-A1 and UT-B1 mRNA abundance was significantly increased in the skin of UP compared with the control (P < 0.01), and, with the decrease of eGFR, the AQP5 expression was significantly increased (P < 0.05). We found that the gene changes were coincident with the corresponding target proteins. The urea transporter subtypes, UT-A1 and UT-B1, were expressed in the skin basal cell layer and exocrine sweat glands. The abundance of UT-A1 and UT-B1 in uremic sweat glands was significantly increased in UP, while the expression of AQP5 was decreased. Conclusion Elimination of urea through the skin by producing sweat is a potential therapeutic strategy for renal failure patients.

Diabetic nephropathy (DN) is the primary cause of end-stage renal disease, 1 and causes cardiovascular mortalities for patients with obesity or diabetes. 2 The typical structural characteristics of DN are thickening of tubular basement membranes and glomerular hypertrophy resulting from the aberrant deposition of the extracellular matrix (ECM) in the kidneys. 3 Additionally, renal dysfunction caused by DN is closely related to ECM deposition in glomerular mesangium and tubulointerstitium. 4 Tubulointerstitial fibrosis and glomerulosclerosis are the key factors of DN. 5,6 Unfortunately, effective therapeutic methods for DN have not been discovered, thus, further exploration of the molecular mechanisms in the pathophysiology of DN is in urgent need. MicroRNAs (miRNAs) are a category of non-coding RNA (ncRNA) molecules with 20-24 nucleotides in length. 7 Dysregulation of miR-NAs has been reported to regulate several biological process during the progression of DN. 8,9 In detail, miRNA-23a/27a attenuates renal fibrosis through muscle-kidney crosstalk in streptozotocin-induced diabetic mice. 10 Furthermore, miR-21 promotes renal tubular extracellular matrix (ECM) synthesis and accumulation to aggravate renal fibrosis in DN. 11 Most recently, miR-325-3p was confirmed to get involved in immobilization-induced suppression of luteinizing hormone translation and secretion. 12 Besides, miR-325-3p suppresses

Purpose/Objectives. Primary small cell esophageal carcinoma (SCEC) represents a rare and aggressive malignancy without any prospective clinical trial or established treatment strategy at present. Although previous studies have indicated similarities between SCEC and small cell lung cancer (SCLC) in terms of their clinical manifestations, pathology, and morphology, very little genetic information is available on this highly malignant tumor. At present, patients with SCEC are staged and treated according to the guidelines established for SCLC. However, early recurrence and distant metastasis are common, and long-time survivors are rare. Current options available for patients with relapsed SCEC are fairly unsatisfactory, and their prognosis is generally poor. Novel therapeutic approaches against SCEC are therefore urgently needed and require a deeper understanding of the underlying genetic mechanisms. The current investigation aims to characterize the gene expression profile and copy number variations (CNVs) in SCEC to clarify molecular markers and pathways that may possess clinical significance. Materials/Methods. De novo expression array was carried out on three matched sets of primary SCEC and adjacent normal tissue samples procured from the institutional tissue bank, utilizing the Affymetrix HG U133 Plus 2.0 Array. After individual tissue normalization, the statistical software GeneSpring GX 12.5 was used to determine differentially expressed genes (DEGs) in the tumors relative to their paired normal tissues. Gene enrichments in addition to functional annotation and gene interaction networks were performed using DAVID 6.8 and STRING 10.0, respectively. A gene alteration was determined to be recurrent if it was observed in at least 2 samples. Chromosomes X and Y were not included in calculations as gender differences are a known source of analysis bias. The DEGs of at least one SCEC sample could be mapped to the CNV regions (fold change (FC) ≥ 2 and false discovery rate (FDR) < 0.01) after gene expression profiling by RefSeq Transcript ID. These overlapped genes were subjected to the functional annotation using DAVID 6.8. In order to elucidate the effect of CNV on mRNA expression, we integrated the genome-wide copy number data and gene expression in 3 paired samples. CNV-associated gene expression aberration (CNV-FC) was calculated for the recurrent DEGs using previously published integrated microarray data as reference. Pearson's correlation coefficient was employed to determine if there was a statistical correlation between the gene expression log2 ratios and their copy numbers using the SPSS 19.0 software. Genes that possessed CNV-FC ≥ 2 and r ≥ 0.6 (p < 0.05) were determined to be genes potentially associated with cancer. Results. High-quality DNA and total RNA were first extracted from both SCEC and normal tissues. Microarray data showed significant upregulation in WNT gene sets and downregulation in the PTEN and notch gene sets in SCEC. Functional annotation showed that genes associated with DNA replicatio...