Genome-wide identification of novel expression signatures reveal distinct patterns and prevalence of binding motifs for p53, nuclear factor-κB and other signal transcription factors in head and neck squamous cell carcinoma

Microarray profiling of ten head and neck cancer lines revealed novel p53 and NF-κB transcriptional gene expression signatures which distinguished tumor cell subsets in association with their p53 status

TSPY potentiates cell proliferation and tumorigenesis by promoting cell cycle progression in HeLa and NIH3T3 cells

BACKGROUND: TSPY is a repeated gene mapped to the critical region harboring the gonadoblastoma locus on the Y chromosome (GBY), the only oncogenic locus on this male-specific chromosome. Elevated levels of TSPY have been observed in gonadoblastoma specimens and a variety of other tumor tissues, including testicular germ cell tumors, prostate cancer, melanoma, and liver cancer. TSPY contains a SET/NAP domain that is present in a family of cyclin B and/or histone binding proteins represented by the oncoprotein SET and the nucleosome assembly protein 1 (NAP1), involved in cell cycle regulation and replication. METHODS: To determine a possible cellular function for TSPY, we manipulated the TSPY expression in HeLa and NIH3T3 cells using the Tet-off system. Cell proliferation, colony formation assays and tumor growth in nude mice were utilized to determine the TSPY effects on cell growth and tumorigenesis. Cell cycle analysis and cell synchronization techniques were used to determine cell cycle profiles. Microarray and RT-PCR were used to investigate gene expression in TSPY expressing cells. RESULTS: Our findings suggest that TSPY expression increases cell proliferation in vitro and tumorigenesis in vivo. Ectopic expression of TSPY results in a smaller population of the host cells in the G(2)/M phase of the cell cycle. Using cell synchronization techniques, we show that TSPY is capable of mediating a rapid transition of the cells through the G(2)/M phase. Microarray analysis demonstrates that numerous genes involved in the cell cycle and apoptosis are affected by TSPY expression in the HeLa cells. CONCLUSION: These data, taken together, have provided important insights on the probable functions of TSPY in cell cycle progression, cell proliferation, and tumorigenesis

Gas5 is an essential lncRNA regulator for self-renewal and pluripotency of mouse embryonic stem cells and induced pluripotent stem cells

Abstract Background The regulatory role of long noncoding RNAs (lncRNAs) have been partially proved in embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Methods In the current study, we investigated mouse ESC (mESC) self-renewal, differentiation, and proliferation in vitro by knocking down a lncRNA, growth arrest specific 5 (Gas5). A series of related indicators were examined by cell counting kit-8 (CCK-8) assay, quantitative reverse-transcription polymerase chain reaction (qRT-PCR), Western blot, alkaline phosphatase staining, propidium iodide (PI) staining, Annexin V staining, competition growth assay, immunofluorescence, and chromatin immunoprecipitation (ChIP)-qPCR. An in vivo teratoma formation assay was also performed to validate the in vitro results. qRT-PCR, fluorescence-activated cell sorting (FACS), alkaline phosphatase staining, and immunofluorescence were used to evaluate the role of Gas5 during mouse iPSC reprogramming. The regulatory axis of Dicer-miR291a–cMyc-Gas5 and the relationship between Gas5 and Tet/5hmC in mESCs was examined by qRT-PCR, Dot blot, and Western blot. Results We identified that Gas5 was required for self-renewal and pluripotency of mESCs and iPSCs. Gas5 formed a positive feedback network with a group of key pluripotent modulators (Sox2, Oct4, Nanog, Tcl1, Esrrb, and Tet1) in mESCs. Knockdown of Gas5 promoted endodermal differentiation of mESCs and impaired the efficiency of iPSC reprogramming. In addition, Gas5 was regulated by the Dicer-miR291a–cMyc axis and was involved in the DNA demethylation process in mESCs. Conclusions Taken together, our results suggest that the lncRNA Gas5 plays an important role in modulating self-renewal and pluripotency of mESCs as well as iPSC reprogramming

The complexity of antisense transcription revealed by the study of developing male germ cells

10.1016/j.ygeno.2005.12.006GENOMICS876681-69