Background/Aims: MicroRNAs (miRNAs, miRs) have emerged as important post-transcriptional regulators in various cancers. miR-543 has been reported to play critical roles in hepatocellular carcinoma and colorectal cancer, however, the role of miR-543 in the pathogenesis of prostate cancer has not been fully understood. Methods: Expression of miR-543 and Raf Kinase Inhibitory Protein (RKIP) in clinical prostate cancer specimens, two prostate cancer cell lines, namely LNCAP and C4-2B, were determined. The effects of miR-543 on proliferation and metastasis of tumor cells were also investigated with both in vitro and in vivo studies. Results: miR-543 was found to be negatively correlated with RKIP expression in clinical tumor samples and was significantly upregulated in metastatic prostate cancer cell line C4-2B compared with parental LNCAP cells. Further studies identified RKIP as a direct target of miR-543. Overexpression of miR-543 downregulated RKIP expression and promoted the proliferation and metastasis of cancer cells, whereas knockdown of miR-543 increased expression of RKIP and suppressed the proliferation and metastasis of cancer cells in vitro and in vivo. Conclusion: Our study demonstrates that miR-543 promotes the proliferation and metastasis of prostate cancer via targeting RKIP.
Accumulating evidences have indicated that aberrant expression of long non-coding RNAs (LncRNAs) is tightly associated with cancer development. Previous studies have reported that lncRNA XIST regulates tumor malignancies in several cancers. However, the underlying mechanism of XIST in prostate cancer remains unclear. In the current study, we found that XIST was down-regulated in prostate cancer specimens and cell lines. Low expression of XIST was correlated with poor prognosis and advanced tumor stage in prostate cancer patients. In gain and loss of function assays, we confirmed that XIST suppressed cellular proliferation and metastasis in prostate cancer both in vitro and in vivo. Furthermore, we found that XIST negatively regulates the expression of miR-23a and subsequently promotes RKIP expression at post-transcriptional level. Consequently, we investigated the correlation between XIST and miR-23a, and identified miR-23a as a direct target of XIST. In addition, over-expression of miR-23a efficiently abrogated the up-regulation of RKIP induced by XIST, suggesting that XIST positively regulates the expression of RKIP by competitively binding to miR-23a. Taken together, our study indicated that lncRNA XIST acts as a tumor suppressor in prostate cancer, and this regulatory effect of XIST will shed new light on epigenetic diagnostics and therapeutics in prostate cancer.
Graphene oxide (GO) has attracted intensive interest in the biomedical field in recent years. We investigate whether the use of functional graphene oxide as an efficient delivery system for delivering specific molecular antitumor therapeutics in vivo could achieve a more excellent antitumor effect. Constitutive activation of signal transducer and activator of transcription 3 (Stat3) promotes survival in a wide spectrum of human cancers. In this paper, we study the in vivo behavior of graphene oxide chemically functionalized with polyethylenimine and polyethylene glycol (GO-PEI-PEG) as a plasmid-based Stat3-specific small interfering RNA (siRNA) carrier in mouse malignant melanoma. The in vivo results indicate significant regression in tumor growth and tumor weight after plasmid-based Stat3 siRNA delivered by GO-PEI-PEG treatment. Moreover, there was no significant side effect from GO-PEI-PEG treatment according to histological examination and blood chemistry analysis in mice. Thus, our work is the first success of using GO-PEI-PEG as a promising carrier for plasmid Stat3 siRNA delivery and down-regulation of Stat3 by a polymer-mediated vehicle and suggests the great promise of graphene in biomedical applications such as cancer treatment.
BackgroundThe involvement of lipid metabolism in tumourigenesis and the progression of clear cell renal cell carcinoma (ccRCC) have been reported. However, the role of phospholipid profile alterations in ccRCC has not yet been systematically explored. In the present study, we compared the phospholipid compositions between ccRCC and paired normal renal tissues.MethodsThe phospholipid compositions of paired ccRCC and normal renal tissues were evaluated using liquid chromatography tandem mass spectrometry (LC/MS/MS). To evaluate the mRNA and protein levels of lysophosphatidylcholine acyltransferase (LPCAT), which converts lysophosphatidylcholine (LPC) to phosphatidylcholine (PC), qRT-PCR, western blotting and immunohistochemistry were performed. The correlations of LPCAT1 expression with clinicopathological features and prognosis were assessed. In addition, siRNAs were used to knockdown LPCAT1 expression in ccRCC cell lines, and its effect on cell proliferation, cell cycle, migration and invasion were investigated.ResultsThe phospholipid compositions of ccRCC and normal renal tissues were significantly different. Multiple LPC species were decreased and corresponding PC species were increased in cancer tissues. The mRNA and protein levels of LPCAT1 were up-regulated in ccRCC tissues compared with normal renal tissues, and LPCAT1 expression was significantly correlated with unfavourable pathological features (higher tumour grade, higher TNM stage and larger tumour size) and overall survival. In cell line experiments, LPCAT1 knockdown depleted PCs, inhibited cell proliferation, migration and invasion and induced cell cycle arrest at the G0/G1 phase.ConclusionSelective changes in PC and LPC composition were observed in ccRCC tissues. The overexpression of LPCAT1 promotes the development and progression of ccRCC, likely through the conversion of LPC to PC.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-017-0525-1) contains supplementary material, which is available to authorized users.
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Keywords:Time-fractional fourth-order reaction-diffusion problem Finite element method Finite difference scheme Caputo-fractional derivative Unconditional stability Optimal a priori error analysis a b s t r a c tIn this article, a finite difference/finite element algorithm, which is based on a finite difference approximation in time direction and finite element method in spatial direction, is presented and discussed to cast about for the numerical solutions of a time-fractional fourth-order reaction-diffusion problem with a nonlinear reaction term. To avoid the use of higher-order elements, the original problem with spatial fourth-order derivative need to be changed into a second-order coupled system by introducing an intermediate variable σ = ∆u. Then the fully discrete finite element scheme is formulated by using a finite difference approximation for time fractional and integer derivatives and finite element method in spatial direction. The unconditionally stable result in the norm, which just depends on initial value and source item, is derived. Some a priori estimates of L 2 -norm with optimal order of convergence O(∆ 2−α t +h m+1 ), where ∆ t and h are time step length and space mesh parameter, respectively, are obtained. To confirm the theoretical analysis, some numerical results are provided by our method.
In this article, a nonlinear fractional Cable equation is solved by a two-grid algorithm combined with finite element (FE) method. A temporal second-order fully discrete two-grid FE scheme, in which the spatial direction is approximated by two-grid FE method and the integer and fractional derivatives in time are discretized by second-order two-step backward difference method and second-order weighted and shifted Grünwald difference (WSGD) scheme, is presented to solve nonlinear fractional Cable equation. The studied algorithm in this paper mainly covers two steps: First, the numerical solution of nonlinear FE scheme on the coarse grid is solved; Second, based on the solution of initial iteration on the coarse grid, the linearized FE system on the fine grid is solved by using Newton iteration. Here, the stability based on fully discrete two-grid method is derived. Moreover, the a priori estimates with second-order convergence rate in time is proved in detail, which is higher than the L1-approximation result with O(τ 2−α + τ 2−β ). Finally, the numerical results by using the two-grid method and FE method are calculated, respectively, and the CPU-time is compared to verify our theoretical results.
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