MicroRNAs (miRNAs) act as important gene regulators in human genomes and their aberrant expression links to many malignancies. We previously identified a different characteristic miRNA expression profile in cervical cancer from that in cervical normal tissues, including the downregulated miR-424. However, the role and mechanism of miR-424 in cervical cancer still remain unknown. Here, we focused on identifying the tumor-suppressive function and clinical significance of miR-424 and exploring the mechanistic relevance by characterizing its target. We showed a significantly decreased expression of miR-424 in 147 cervical cancer tissues versus 74 cervical normal tissues by performing quantitative RT-PCR. In 147 cervical cancer tissue samples, low-level expression of miR-424 was positively correlated with poor tumor differentiation, advanced clinical stage, lymph node metastasis and other poor prognostic clinicopathological parameters. Further in vitro observations showed that enforced expression of miR-424 inhibited cell growth by both enhancing apoptosis and blocking G1/S transition, and suppressed cell migration and invasion in two human cervical cancer cell lines, SiHa and CaSki, implying that miR-424 functions as a tumor suppressor in the progression of cervical cancer. Interestingly, overexpression of miR-424 inhibited the expression of protein checkpoint kinase 1 (Chk1) and phosphorylated Chk1 (p-Chk1) at residues Ser345 and decreased the activity of luciferase-reporter containing the 3'-untranslated region (UTR) of Chk1 with predicted miR-424-binding site. Moreover, miR-424 expression levels were inversely correlated with Chk1 and p-Chk1 protein levels in both cervical cancer and normal tissues. Furthermore, RNAi-mediated knockdown of Chk1 decreased matrix metalloproteinase 9 expression and phenocopied the tumor suppressive effects of miR-424 in cell models. Taken together, our results identify a crucial tumor suppressive role of miR-424 in the progression of cervical cancer at least partly via upreglating the expression of Chk1 and p-Chk1, and suggest that miR-424 might be a candidate of prognostic predictor or an anticancer therapeutic target for cervical cancer patients.
Background:Chemo-resistance is one of the key causal factors in cancer death and emerging evidences suggest that microRNAs (miRNAs) have critical roles in the regulation of chemo-sensitivity in cancers. Cervical cancer is one of the most common malignancies in women and insensitive to chemotherapy clinically.Methods:The differentially expressed miRNAs in cervical squamous cell carcinoma tissues were screened by using a microarray platform (μParaflo Sanger miRBase release 13.0). The expression of miR-375 was determined by stem-loop RT–PCR using 23 clinical cervical cancer samples and 2 cervical cancer cell lines. We exogenously upregulated miR-375 expression in SiHa and Caski cells using a pre-miRNA lentiviral vector transfection and observed its impact on paclitaxel sensitivity using MTS. The cells that stably overexpressed miR-375 were subcutaneously injected into mice to determine tumour growth and chemo-sensitivity in vivo.Results:Twenty-one differentially expressed miRNAs were found by miRNA microarray between pro- and post-paclitaxel cervical cancer tissues. Of those, miR-375 showed consistent high expression levels across paclitaxel-treated cervical cells and tissues. Paclitaxel induced upregulated miR-375 expression in a clear dose-dependent manner. Forced overexpression of miR-375 in cervical cancer cells decreased paclitaxel sensitivity in vitro and in vivo.Conclusion:Collectively, our results suggest that miR-375 might be a therapeutic target in paclitaxel-resistant cervical cancer.
A tomography system is presented that uses wavelength-scanned direct absorption of two transitions of a target species (NH 3 in the demonstration experiment) to determine the distributions of gas concentration and temperature. The absorption measurements are performed simultaneously from four platforms that each rotate a beam from a single laser through an 11 • arc, acquiring a data set from all four laser platforms in 100 ms to enable observation of dynamic flow events. The laser is wavelength scanned through two absorption transitions with different internal energy producing two sets of equations with species mole fraction and temperature as independent variables. The mole fraction and temperature distributions are reconstructed using the algebraic reconstruction technique (ART) for this set of incomplete projections. A numerical simulation is used to evaluate the measurement accuracy for measurements of an NH 3 mixture escaping from an open pipe. This phantom distribution is then realized in the laboratory and the measurement strategy is demonstrated using a tunable diode laser absorption spectroscopy (TDLAS) measurement using a single laser near 1.5 μm to scan adjacent transitions in NH 3 . The reconstruction of NH 3 concentration and gas temperature is compared with independently determined values to illustrate the fidelity of the tomographically reconstructed distributions for the NH 3 mole fraction assuming a fixed temperature and for unknown mole fraction and temperature. Potential extensions of this research in the future include evaluation of other reconstruction algorithms and investigation of the dynamic distribution of various gases for combustion diagnostics.
In the present study, two experiments were performed to study the effects of feeding fermented corn and soybean meal mixed feed (FMF) with Bacillus subtilis and Enterococcus faecium to lactating sows on the performance of the sows and their progeny. In experiment 1, 60 sows were allocated to the following three dietary treatments: 1) sows fed a corn and soybean meal basal diet (control) from day 3 before parturition to weaning, 2) sows fed a diet with 7.5% FMF, and 3) sows fed a diet with 15% FMF. Results indicated that feeding 15% FMF significantly improved (P < 0.05) the sows' ADFI, the individual piglet weaning weights, and piglet weight gain and reduced (P < 0.05) the backfat loss of sows compared with the control group. However, the 7.5% FMF treatment did not alter the performance of the sows or their progeny. Therefore, we considered the level of 15% FMF to be more efficient than 7.5% FMF. To verify the results of experiment 1, we performed experiment 2, in which 60 sows at 111 d of gestation were allocated into the following two dietary treatments: 1) sows fed a basal lactation diet (control) from d 111 of gestation to weaning and 2) sows fed a basal diet with 15% FMF. Compared with the control group, 15% FMF inclusion significantly increased (P < 0.05) the sows' ADFI, litter weight gain, and individual piglet weight gain during lactation and markedly decreased the backfat loss of sows (P < 0.05) and piglet diarrhea incidence (P < 0.05). Additionally, the milk yield and IgA contents of the milk in sows fed 15% FMF were greater (P < 0.05) than those of the control group. Furthermore, the apparent total tract digestibility of GE, DM, and total P of sows was increased (P < 0.05) with 15% FMF supplementation. Therefore, the present study indicates that supplementing sow diets with 15% FMF from parturition to weaning has the potential to 1) increase sow ADFI, milk production, milk IgA content, and nutrient digestibility and promote sow reproductive performance by shortening the weaning-to-estrous interval and 2) promote the growth performance of their progeny and decrease diarrhea incidence.
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