Differential mRNA expression profiling of oral squamous cell carcinoma by high-throughput RNA sequencing

Differentially expressed genes are thought to regulate the development and progression of oral squamous cell carcinomas （OSCC）. The purpose of this study was to screen differentially expressed mRNAs in OSCC and matched paraneoplastic normal tissues, and to explore the intrinsic mechanism of OSCC development and progres- sion. We obtained the differentially expressed mRNA expression profiles in 10 pairs of fresh-frozen OSCC tissue specimens and matched paraneoplastic normal tissue specimens by high-throughput RNA sequencing. By using Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses, the functional significance of the differentially expressed genes were analyzed. We identified 1,120 sig- nificantly up-regulated mRNAs and 178 significantly down-regulated mRNAs in OSCC, compared to normal tissue. The differentially expressed mRNAs were involved in 20 biological processes and 68 signal pathways. Compared to adjacent normal tissue, the expression of MAGEAll was up-regulated; TCHH was down-regulated. These find- ings were verified by real-time PCR. These differentially expressed mRNAs may function as oncogenes or tumor suppressors in the development and progression of OSCC. This study provides novel insights into OSCC. However, further work is needed to determine if these differentially expressed mRNAs have potential roles as diagnostic bio- markers and candidate therapeutic targets for OSCC.

Metathesis of 1-butene and 2-butene to propene over Re_2O_7 supported on macro-mesoporous γ-alumina prepared via a dual template method

Macro-mesoporous γ-alumina support（MMA） was prepared by a sol-gel route in aqueous medium using pseudo-boehmite as aluminum source and polystyrene microspheres and Pluronic P123 as hard and soft dual templates,respectively.MMA had a BET specific surface area of about 259 m2 g-1,total pore volume of about 1.61 cm3 g-1,macropore diameter of about 102 nm,and mesopore diameter of about 14 nm.Re2O7/MMA and conventional Re2O7/Al2O3 were prepared by a incipient-wetness impregnation method,and their catalytic performances in the metathesis of 1-butene and 2-butene were tested in a fixed-bed tubular reactor.The result showed that Re2O7/MMA possessed higher activity and far longer working life-span than conventional Re2O7/Al2O3.

Preparation of mesoporous alumina with large pore size and their supported rhenium oxide catalysts in metathesis of 1-butene and 2-butene to propene

Mesoporous γ-aluminas with large pore size （up to 19 nm, denoted as MAI9） are prepared from dispersed pseudo-boehmite using pluronic P123 as template. It is found that these mesoporous alumina supported rhenium oxide catalysts were more active and have far longer working life-span in gas-phase metathesis of 1-butene and 2-butene to propene than rhenium oxide on conventional alumina with small pore size （5 nm）. At 60 ℃ and atmospheric pressure with WHSV = 1 h^-1, the similar stable conversions of butene （ca. 55%） for all the 13 wt% Re207/alumina catalysts were obtained near the chemical equilibrium, and the stable working life-spans of Re2OT/MA19 were far longer than that of Re2O7/A1203, being about 70 h and 20 h, respectively.

PYK2 mediates the BRAF inhibitor (vermurafenib)-induced invadopodia formation and metastasis in melanomas

Objective:The BRAF inhibitor,vemurafenib,has been widely used in the treatment of patients with melanoma-bearing BRAFV600E mutations.While the initial response to vemurafenib is usually excellent,the majority of patients eventually develop resistance and metastatic disease.However,the underlying molecular mechanism remains elusive.The objective of this study was therefore to identify additional molecular targets responsible for vemurafenib resistance.Methods:Western blots and immunohistochemistry analyses were used to evaluate expressions of PYK2 and p-PYK2 in cultured cells and melanoma tissue microarrays.The relationships of p-PYK2 with clinicopathological parameters were statistically analyzed.Invadopodia cell invasion,and a Ca2+assay were used to determine the effect of vemurafenib resistance-induced p-PYK2 on melanoma progression.A mouse model was used to assess the effects of PYK2 on melanoma metastasis.Results:Elevated p-PYK2 levels were detected in vemurafenib-resistant melanoma cells,and PYK2 was shown to regulate invadopodia formation in melanoma cells.Vemurafenib triggered invadopodia formation by activation of PYK2.Inhibition of PYK2 with either shRNA or the small molecule inhibitor,PF562711,dramatically reduced vemurafenib-induced invadopodia formation.Furthermore,knockdown of PYK2 significantly reduced melanoma lung metastasis in vivo.Increased expressions of p-PYK2 in melanoma patients were positively correlated with advanced stage(P=0.002),metastasis(P<0.001),and Clark grade(P<0.001),and were also associated with short overall survival[hazard ratio(HR)=3.304,P=0.007]and progression-free survival(HR=2.930,P=0.001).Conclusions:PYK2 mediated vemurafenib-induced melanoma cell migration and invasion.Inhibition of PYK2 resensitized melanoma cells to vemurafenib.Phospho-PYK2 was a prognostic biomarker in melanoma patients.

Overexpression of inhibinα(1-32)fusion protein promotes apoptosis and cell cycle arrest in a cervical cancer cell model(Hela cells)

Inhibins play important roles in the reproductive system. To evaluate whether inhibin α (1-32) fusion protein plays a role in cervical cancer growth, the plasmid pVAX-inhα was constructed and its effect on proliferation and apoptosis of the human cervical cancer cell line (Hela) was checked by flow cytometry and real-time PCR. The expression and localization of inhibin α protein were detected by RT-PCR and confocal mi- croscopy which showed that inhibin α protein was expressed and localized in the nucleus of Hela cells. Over ex- pression of inhibin α gene significantly induced cell apoptosis and ceased S phase of cell cycle. Furthermore, cell proliferation was significantly suppressed 96 h post-transfection and mRNA level of anti-apoptosis genes (Bcl-2, NFκB) were decreased but pro-apoptosis genes (Bax, wild type p53) and inhibin co receptor (TGFβR3) were increased, indicating that inhibin, through its co-receptor, might activate apoptotic and cell growth cascades which regulate proliferation and apoptosis in Hela cells. These results suggest that inhibin α (1-32) fusion pro- tein, located in the cell nucleus, can regulate Hela cells growth and apoptosis by induction of apoptotic pathways such as NFκB, Bcl-2 and p53 families. These findings may have a significant impact on future research regarding cervical cancer cell lines.