Stabilization of Snail by HIF-1α and TNF-α is required for hypoxia-induced invasion in prostate cancer PC3 cells.

Hypoxia has been involved in the development of tumor by regulating the expression of invasiveness-associated genes. However, the specific function of hypoxia in cancer cell invasion is still unclear. The aim of the present study was to determine the role of hypoxia in invasion of prostate cancer PC3 cells and to investigate the underlying mechanisms. We found that hypoxia significantly increased the invasive activity of PC3 cells, via up-regulation of the expression of hypoxia inducible factor 1α (HIF-1α) and the autocrine production of tumor necrosis factor α (TNF-α). More important, TNF-α cooperated with HIF-1α in promoting stabilization of Snail, a transcriptional repressor of E-cadherin expression, which lead to the up-regulation of invasiveness-associated genes MMP-9, fibronectin and vimentin. Snail silencing by specific siRNA significantly inhibited hypoxia-induced invasion of PC3 cells, indicating an essential role of Snail in conferring the malignant phenotype to cancer cells under hypoxic conditions. In conclusion, our data demonstrate that hypoxia promoted the invasiveness of prostate cancer PC3 cells via HIF-1α- and TNF-α-induced stabilization of Snail, suggesting a signaling mechanism involving HIF-1α/TNF-α/Snail that mediates invasiveness hypoxic tumor cells in the absence of neoangiogenesis.

Nanopore with Transverse Nanoelectrodes for Electrical Characterization and Sequencing of DNA.

A DNA sequencing device which integrates transverse conducting electrodes for the measurement of electrode currents during DNA translocation through a nanopore has been nanofabricated and characterized. A focused electron beam (FEB) milling technique, capable of creating features on the order of 1 nm in diameter, was used to create the nanopore. The device was characterized electrically using gold nanoparticles as an artificial analyte with both DC and AC measurement methods. Single nanoparticle/electrode interaction events were recorded. A low-noise, high-speed transimpedance current amplifier for the detection of nano to picoampere currents at microsecond time scales was designed, fabricated and tested for future integration with the nanopore device.

SATB1 overexpression regulates the development and progression in bladder cancer through EMT.

The global gene regulator Special AT-rich sequence-binding protein-1 (SATB1) has been reported to induce EMT-like changes and be associated with poor clinical outcome in several cancers. This study aims to evaluate whether SATB1 affects the biological behaviors of bladder transitional cell carcinoma (BTCC) and further elucidate if this effect works through an epithelial-mesenchymal transition (EMT) pathway. The expression of SATB1, E-cadherin (epithelial markers), vimentin (mesenchymal markers) in BTCC tissues and adjacent noncancerous tissues, as well as in two cell lines of bladder cancer were investigated. Whether the SATB1 expression is associated with clinicopathological factors or not was statistically analyzed. Cell invasion and migration, cell cycle, cell proliferation and apoptosis were evaluated in SATB1 knockdown and overexpressed cell lines. Our results showed that the expression of SATB1 was remarkably up-regulated both in BTCC tissues and in bladder cancer cell lines with high potential of metastasis. The results were also associated with EMT markers and poor prognosis of BTCC patients. Moreover, SATB1 induced EMT processes through downregulation of E-cadherin, upregulation of E-cadherin repressors (Snail, Slug and vimentin). SATB1 also promoted cell cycle progression, cell proliferation, cell invasion and cell migration, but did not alter cell survival. In conclusion, our results suggest that SATB1 plays a crucial role in the progression of bladder cancer by regulating genes controlling EMT processes. Further, it may be a novel therapeutic target for aggressive bladder cancers.

Short hairpin RNA targeting FOXQ1 inhibits invasion and metastasis via the reversal of epithelial-mesenchymal transition in bladder cancer.

The epithelial-mesenchymal transition (EMT) promotes cancer invasion and metastasis, however, the integrative mechanisms that coordinate the process are incompletely understood. In this study, we defined a pivotal functional role for the Forkhead transcription factor FOXQ1 in regulating EMT in bladder cancer. We initially investigated the expression of FOXQ1, TGF-ß1 and EMT biomarkers E-cadherin, Vimentin in 65 cases of bladder transitional cell carcinoma (BTCC) specimens by reverse transcription-polymerase chain reaction (RT-PCR), western blot analysis and immunohistochemistry. Search results indicated that FOXQ1 expression was inversely correlated to E-cadherin, but positively to TGF-ß1 and Vimentin in patients with BTCC (P<0.05). Furthermore, we aimed to construct short hairpin RNA (shRNA) expression plasmids against the FOXQ1 gene and transfect shRNAs into high metastatic potential human bladder cancer T24 cells with Lipofectamine 2000. RNAi-mediated suppression of FOXQ1 expression reversed the EMT process accompanied by upregulation of E-cadherin, as well as a loss expression of Vimentin in highly invasive T24 cells (P<0.05). The inhibition of FOXQ1 expression with shRNA vector also led T24 cells to acquire an epithelial cobblestone phenotype, significantly reduced motility and subsequent invasiveness of bladder cancer cells (P<0.05). In conclusion that FOXQ1 may be a novel EMT-inducing transcription factor through controlling the expression of E-cadherin and aggressiveness of cancer cells and targeting the transcription factor FOXQ1 could hence serve as a novel therapeutic strategy for cancer patients.