Background: We postulated that microRNAs (miRNAs) might be involved in hepatocellular carcinoma (HCC) targeted chemotherapy with paclitaxel. This study sought to generate a list of potential miRNA-based biomarkers and their potential targets to better understand the response to paclitaxel treatment in HCC. Methods: Cell viability proliferation assays were conducted to test the sensitivity of the HepG2 cells to paclitaxel. The morphological changes of apoptosis were assessed with 4′,6-diamidino-2-phenylindole staining. Differential expression patterns of miRNA in the HepG2 cells either treated or not treated were analyzed using miRNA microarrays. Results: The array experiments have identified 54 miRNAs whose basal expression levels differed by >2-fold and p < 0.05 between the two phenotypic groups. The data were validated by a quantitative real-time PCR of 8 selected miRNAs (miR-21, miR-1274a, miR-1260, miR-1290, miR-508-5p, miR-877, miR-1246, miR-183*). The PI3K/Akt, mitogen-activated protein kinase (MAPK), TGF-β, ErbB, p53, cell cycle, mammalian target of rapamycin, and Jak-STAT signaling pathways were involved in paclitaxel-induced apoptosis. Conclusions: The manipulation of one or more of these miRNAs could be an important approach for the improved management of paclitaxel therapy.

Kashin-Beck Disease (KBD) is an endemic osteochondropathy, the pathogenesis of which remains unclear now. In this study, we compared gene expression profiles of articular cartilage derived respectively from KBD patients and normal controls. Total RNA were isolated, amplified, labeled and hybridized to Agilent human 1A 22 k whole genome microarray chip. qRT-PCR was conducted to validate our microarray data. We detected 57 up-regulated genes (ratios ≥2.0) and 24 down-regulated genes (ratios ≤0.5) in KBD cartilage. To further identify the key genes involved in the pathogenesis of KBD, Bayesian analysis of variance for microarrays(BAM) software was applied and identified 12 potential key genes with an average ratio 6.64, involved in apoptosis, metabolism, cytokine & growth factor and cytoskeleton & cell movement. Gene Set Enrichment Analysis (GSEA) software was used to identify differently expressed gene ontology categories and pathways. GSEA found that a set of apoptosis, hypoxia and mitochondrial function related gene ontology categories and pathways were significantly up-regulated in KBD compared to normal controls. Based on the results of this study, we suggest that chronic hypoxia-induced mitochondrial damage and apoptosis might play an important role in the pathogenesis of KBD. Our efforts may help to understand the pathogenesis of KBD as well as other osteoarthrosis with similar articular cartilage lesions.

Background: Kashin-Beck Disease (KBD) is an endemic osteochondropathy. Mycotoxins are believed to play an important role in the pathogenesis of KBD. Because the molecular mechanism of mycotoxin-induced cartilage lesions remains unclear, there is not effective treatment for KBD now. To identify key genes involved in the mycotoxin-induced cartilage lesions, we compared the expression profiles of mycotoxin-related genes (MRG) between KBD cartilage and healthy cartilage. Methods: Total RNA was isolated from cartilage samples, following by being amplified, labeled and hybridized to Agilent human whole genome microarray chip. qRT-PCR was conducted to validate the microarray data. 1,167 MRG were derived from the environmentally related genomic database Toxicogenomics. The microarray data of MRG was subjected to single gene and gene ontology (GO) expression analysis for identifying differently expressed genes and GO. Results: We identified 7 up-regulated MRG and 2 down-regulated MRG in KBD cartilage, involved in collagen, apoptosis, metabolism and growth & development. GO expression analysis found that 4 apoptosis-related GO and 5 growth & development-related GO were significantly up-regulated in KBD cartilage. Conclusions: Based on the results of previous and our studies, we suggest that mycotoxins might contribute to the development of KBD through dysfunction of MRG involved in collagen, apoptosis and growth & development in cartilage.