A regulator of the protein phosphatase 2A (PP2A), a4, has been implicated in a variety of functions that regulate many cellular processes. To explore the role of a4 in human cell transformation and tumorigenesis, we show that a4 is highly expressed in human cells transformed by chemical carcinogens including benzo(a)pyrene, aflatoxin B 1 , N-methyl-N 0 -nitro-N-nitrosoguanidine, nickel sulfate and in several hepatic and lung cancer cell lines. In addition, overexpression of a4 was detected in 87.5% (74/80) of primary hepatocellular carcinomas, 84.0% (21/25) of primary lung cancers and 81.8% (9/11) of primary breast cancers, indicating that a4 is ubiquitously highly expressed in human cancer. Functional studies revealed that elevated a4 expression results in an increase in cell proliferation, promotion of cell survival and decreased PP2A-attributable activity. Importantly, ectopic expression of a4 permits non-transformed human embryonic kidney cells (HEKTER) and L02R cells to form tumors in immunodeficient mice. Furthermore, we show that the highly expressed a4 in transformed cells or human tumors is not regulated by DNA hypomethylation. A microRNA, miR-34b, that suppresses the expression of a4 through specific binding to the 3 0 -untranslated region of a4 is downregulated in transformed or human lung tumors. Taken together, these observations identify that a4 possesses an oncogenic function. Reduction of PP2A activity due to an enhanced a4-PP2A interaction contributes directly to chemical carcinogen-induced tumorigenesis.
MicroRNAs (miRNAs) represent a group of novel therapeutic small molecules involved in the management of lung cancer treatment. Our study aims to investigate the potential role of miRNAs in the treatment of non-small cell lung cancer (NSCLC). Human miRNA microarray was performed in 60 recurrent NSCLC patient tissue samples following radiotherapy and their adjacent normal tissues. miRNA profiling results were validated using quantitative real-time PCR. Inner cell radiosensitivity and endogenous miRNA expression was determined by colony-formation assay and RT-PCR. We determined the effect of miRNA on cell proliferation, survival and metastasis; tumor xenografts were taken to identify the presence of miRNA in vivo. miRNA panel results indicated that a total of 14 miRNAs were differentially expressed in the recurrent NSCLC samples. In our study, miRNA-95 was highly overexpressed in recurrent NSCLC cells. Knockdown of miRNA-95 expression increased the radiosensitivity of NSCLC, promoted tumor cell apoptosis and decreased cellular proliferation. In vivo assays demonstrated reduced tumor growth and resistance to radiation in tumor xenografts by downregulating miRNA-95. Our study demonstrated a potential therapeutic measure of miRNA-95 as a radiosensitive marker for the treatment of non-small lung cancer.
The equilibrium geometries of three isomeric hexapyrrolidine C(60) adducts with T(h), D(3), and S(6) symmetries are optimized by means of the B3LYP method at the 6-31G basis sets in this paper. On the basis of the optimized structures, the excited state and third-order nonlinear optical properties, such as third-harmonic generation (THG), electric-field-induced second-harmonic generation (EFISHG), and degenerate four-wave mixing (DFWM), and two-photon absorption (TPA) cross sections, delta, are calculated by using the TDB3LYP model based on the 6-31G level coupled with the sum-over-states (SOS) method. The computational results show that the transition energies from S(0) to S(1) of the T(h) hexaadduct and the D(3) hexaadduct have a remarkable blue shift by comparison with that of the C(60) parent. These results are in agreement with experimental ones. However, the first singlet excitation energy of the S(6) hexaadduct has a red shift compared with that of the C(60) parent. Accordingly, we predict that different positions located by six addends may result in the different spectrum properties. Finally, the two-photon absorption cross sections indicate that the largest average value of resonant TPA, delta, of the D(3) hexaadduct has a red shift compared with those of the T(h) and S(6) hexaadducts.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.