Emerging roles of piRNAs in cancer: challenges and prospects.

PiRNAs are a small class of non-coding small RNAs newly discovered in recent years. Millions of piRNAs have been discovered to date, and more than 20,000 piRNA genes have been found in the human genome. Due to the relatively small number of studies related to piRNA, our understanding of piRNAs is very limited. Currently, the clear biological function of piRNAs is transposon mobilization inhibition by promoting transcript degradation and regulating chromatin formation. In addition, piRNAs can form piRNA-PIWI protein complexes with some members of the PIWI branch of the Argonaute protein. Based on these biological functions, piRNAs and PIWI proteins are important in maintaining the genomic integrity of germline cells. Because of this, the popularity of piRNAs research has been focused on its role in germline cells for a long time after the discovery of piRNAs. As the field of research expands, there is growing evidence that piRNAs and PIWI proteins are abnormally expressed in various types of cancers, which may be potential cancer biomarkers and cancer therapeutic targets. In this review, we will focus on the relationship between piRNAs and PIWI proteins and cancers based on previous research, as well as their significance in cancer detection, grading and treatment.

Long noncoding RNA PANDA promotes esophageal squamous carcinoma cell progress by dissociating from NF-YA but interact with SAFA.

Esophageal squamous cell carcinoma (ESCC) is one of the major global health problems, especially in Asia. Long non-coding RNAs (lncRNAs) have been increasingly identified and characterized in almost every aspect of biology, especially in cancer biology. This research desires to explore the regulatory mechanism of lncRNA PANDA (PANDA) on ESCC process. Quantitative real-time PCR (qRT-PCR) was carried out to detect the PANDA expression, which was up-regulated in matched cancerous tissues and adjacent noncancerous tissues from 134 patients and 9 ESCC cell lines. Higher expression of PANDA in ESCC tissues was associated with TNM stage, advanced clinical stage, and shorter overall survival of ESCC patients by MTT, EDU, colony formation assay and flow cytometry in KYSE180 and KYSE450 cells. Exogenous down-regulation of PANDA expression significantly suppressed ESCC cells proliferation and colony formation by arresting G1-S checkpoint transition in vitro, and retarded the development of tumors in vivo. Meanwhile, qRT-PCR and western blot assays showed that depletion of PANDA reduced E2F1, cyclinD1, cyclinD2, cyclinE1 and Bcl-2 expression. RIP showed the interaction between PANDA and NF-YA or SAFA. Our findings suggested that, PANDA drifted away from NF-YA to promote the expression of NF-YA-E2F1 co-regulated proliferation-promoting genes, and to limit the cell apoptosis. In addition, PANDA binds SAFA to switch on the tumor proliferation program through CyclinD1/2-Cyclin E1 and Bcl-2 pathways. PANDA could serve as a potential prognostic biomarker and therapeutic target for ESCC.

Trichostatin differentially regulates Th1 and Th2 responses and alleviates rheumatoid arthritis in mice.

OBJECTIVE: Histone deacetylase inhibitors have shown suppressive effects on tumor growth and in some autoimmune diseases. However, the molecular mechanisms of their effects are not very clear. The purpose of this study was to investigate the effects of trichostatin A (TSA) on collagen-induced rheumatoid arthritis (CIA) in a mouse model and its underlying mechanisms. METHODS: CIA was induced in DBA/1 mice with type II collagen. Paws were scored to assess disease severity. Inflammation of joints was evaluated by histological examination. Real-time PCR was used to determine cytokine mRNA levels. Cytokine production in serum and in supernatants from dendritic to T cell co-cultures was measured by ELISA. T cell proliferation was determined using [(3)H] incorporation. Intracellular cytokine staining was used to measure interferon gamma (IFN-γ)- and interleukin (IL)-4-producing T cells in splenocytes. Chromatin immunoprecipitation was used to examine histone H3 and H4 acetylation. RESULTS: TSA potently suppressed the severity of arthritis and type II collagen-specific T cell responses in CIA. IFN-γ expression was high in CIA mice, but was inhibited by TSA treatment either at the same time as immunization or at the onset of arthritis manifestation. T cells from TSA-treated mice produced higher levels of IL-4 than cells from the control group. TSA predominantly suppressed Th1 cell proliferation in vitro by induction of apoptosis. In addition, TSA enhanced IL-4 gene expression of in vitro differentiated Th2 cells, and the mechanism is associated with an increased level of histone acetylation in the IL-4 gene promoter. CONCLUSIONS: While TSA selectively suppresses a Th1 response by inducing apoptosis, it upregulates IL-4 expression probably by increasing histone H3 and H4 acetylation of the IL-4 gene promoter. We conclude that TSA can induce a Th1/Th2 balance in vivo and exert protective effects on CIA.