Impact of Nischarin on EMT regulators in breast cancer cell lines.

Nischarin is an integrin-binding protein, which is well known as a novel tumor suppressor. In breast cancer, Nischarin serves a critical role in breast cancer cell migration and invasion. However, the molecular mechanism underlying the role of Nischarin remains unclear. Recent findings have demonstrated that epithelial-mesenchymal transition (EMT) increases the capacity of cell migration and invasion. As a member of the integrin family, it was hypothesized that Nischarin may regulate cellular processes via various signaling pathways associated with the EMT process. The present study detected the mRNA levels of EMT regulators via reverse transcription-quantitative PCR and related protein levels via western blotting in breast cancer cells, following NISCH-overexpression and -knockdown. The results demonstrated that Nischarin inhibits cell proliferation, migration and invasion in breast cancer cells. Furthermore, when the NISCH gene was overexpressed, the relative mRNA level of E-cadherin was increased, while the relative mRNA levels of several transcription factors, such as Snail, ZEB1, N-cadherin, Slug, Twist1 and vimentin, decreased. When NISCH was silenced, these results were reversed. The present results demonstrated that Nischarin suppresses cell migration and invasion via inhibiting the EMT process.

The genomic mutation spectrums of breast fibroadenomas in Chinese population by whole exome sequencing analysis.

Fibroadenomas (FAs) are the most common fibroepithelial lesions and the most common benign tumors of the breast in women of reproductive age. Although MED12 mutations, an overwhelming majority of all mutations, and some other gene mutations have been found in FAs, the genomic landscapes of FAs are still not completely clear and the genomic mutation spectrums of FAs in Chinese population remains unknown. Here, by performing whole exome sequencing of 12 FAs and the corresponding normal breast tissues in Chinese Han population, we observed the somatic and germline landscapes of genetic alterations. We identified 16 recurrently mutated genes with 37 nonsynonymous or frameshift somatic mutations and 27 recurrent somatic copy number variants (CNVs). In these mutated genes, MED12 was the most common in FAs, harboring 6 nonsynonymous/frameshift somatic mutations and 1 CNV. In addition, 6 germline mutations of tumor susceptibility genes in 5 FAs were identified and the tumor mutational burden of the 5 FAs was significantly higher than the other 7 FAs without germline mutations. This study provides genomic mutation spectrums of FAs in Chinese population and expand the genetic spectrum of FAs.

Identification of compounds from Paris polyphylla (ChongLou) active against Dactylogyrus intermedius.

The present study was designated to ascertain the anthelmintic activity of the rhizomes of Paris polyphylla and to isolate and characterize the active constituents. The methanol extract from rhizomes of P. polyphylla showed significant anthelmintic activity against Dactylogyrus intermedius with the median effective concentration (EC50) 22.5 mg L(-1). Based on this finding, the methanol extract was fractionated by silica gel column chromatography in a bioassay-guided fractionation yielding 2 bioactive compounds, the structures of these compounds were elucidated as formosanin C and polyphyllin VII. The in vivo tests revealed that formosanin C and polyphyllin VII were significantly effective against D. intermedius with EC50 values of 0.6 and 1.2 mg L(-1), respectively. The acute toxicities (LC50) of formosanin C and polyphyllin VII for grass carp were 2.8 and 2.9 mg L(-1), respectively. The overall results provide important information for the potential application of formosanin C and polyphyllin VII in the therapy of serious infection caused by D. intermedius.