No inherent reason exists to impose an upper-age limit for breast cancer screening; however, more data are needed on women's preferences for screening strategies.

Aberrant expression of miR-196a has been frequently reported in different cancers including pancreatic cancer. However, its function in pancreatic cancer has not been fully elucidated. Here, we investigated the expression pattern and the biological role of miR-196a in pancreatic cancer cell lines, as well as its interaction with a metastasis-related gene, nuclear factor-kappa-B-inhibitor alpha (NFKBIA). We demonstrated that miR-196a was up-regulated in human pancreatic cancer cell lines compared with immortalized pancreatic ductal epithelial cells by means of microRNAs microarray and qRT-PCR. Furthermore, down-regulation of miR-196a in PANC-1 suppressed its proliferation and migration with an increase in G0/G1 transition and decreased expression of Cyclin D1 and CDK4/6. Meanwhile, an increased expression in E-cadherin and decreased expression in N-cadherin and Vimentin were also observed. We identified a novel miR-196a target, NFKBIA, and down-regulation of miR-196a enhanced the expression of NFKBIA protein. Luciferase assay confirmed that NFKBIA was a direct and specific target of miR-196a. Silencing NFKBIA in PANC-1 cells enhanced its proliferation and migration. Taken together, our findings indicate that miR-196a is highly expressed in pancreatic cancer cell lines, and may play a crucial role in pancreatic cancer proliferation and migration, possibly through its downstream target, NFKBIA. Thus, miR-196a may serve as a potential therapeutic target for pancreatic cancer.

Osteoarthritis (OA) is the most common degenerative disease of the synovial joint. The synovial membrane is responsible for the inflammatory reaction leading to the secretion of macrophage-derived pro-inflammatory cytokines, such as IL-6. Suppressing IL-6 over-expression in synovial fibroblasts (SF) is a promising method to prevent OA development and progression, in which the prerequisite is the elucidation of the molecular mechanisms underlying IL-6 over-expression in SF. Currently, there are few reports concerning epigenetic modifications in IL-6 in OA SF. In the present study, we attempted to investigate this phenomenon. SF over-expressing IL-6 was collected from OA patients. DNA hypomethylation and histone hyperacetylation were observed in the IL-6 promoter regions in OA SF compared with normal SF. No differences in the status of H3K9 di-methylation, H3K27 tri-methylation and H3K4 tri-methylation were observed in the IL-6 promoter regions between normal and OA SF. DNA (cytosine-5-)-methyltransferase 3 alpha (Dnmt3a) overexpression and anacardic acid (histone acetyltransferase inhibitor) treatment increased DNA methylation and decreased histone acetylation in the IL-6 promoter, and IL-6 over-expression in OA SF was suppressed. These observations provide deeper insight into the pathogenesis of OA and can be used to design new drugs and develop new therapeutic methods to treat OA.

Regulatory T (Treg) cells are one of the major immunosuppressive cell types in cancer and a potential target for immunotherapy, but targeting tumor-infiltrating (TI) Treg cells has been challenging. Here, using single-cell RNA sequencing of immune cells from renal clear cell carcinoma (ccRCC) patients, we identify two distinct transcriptional fates for TI Treg cells, Fate-1 and Fate-2. The Fate-1 signature is associated with a poorer prognosis in ccRCC and several other solid cancers. CD177, a cell surface protein normally expressed on neutrophil, is specifically expressed on Fate-1 TI Treg cells in several solid cancer types, but not on other TI or peripheral Treg cells. Mechanistically, blocking CD177 reduces the suppressive activity of Treg cells in vitro, while Treg-specific deletion of Cd177 leads to decreased tumor growth and reduced TI Treg frequency in mice. Our results thus uncover a functional CD177+ TI Treg population that may serve as a target for TI Treg-specific immunotherapy.