Purpose To investigate the involvement of hsa-microRNA-195-5p (miR-195) in progression and prognosis of human prostate cancer (PCa). Experimental Design qRT-PCR was performed to detect miR-195 expression in both PCa cell lines and clinical tissue samples. Its clinical significance was statistically analyzed. The roles of miR-195 and its candidate target gene ribosomal protein S6 kinase, 70kDa, polypeptide 1 (RPS6KB1) in PCa progression were confirmed based on both in vitro and in vivo systems. Results MiR-195 downregulation in PCa tissues was significantly associated with high Gleason score (P=0.001), positive metastasis failure (P<0.001) and biochemical recurrence (BCR, P<0.001). Survival analysis identified miR-195 as an independent prognostic factor for BCR-free survival of PCa patients (P=0.022). Then, we confirmed the tumor suppressive role of miR-195 through PCa cell invasion, migration and apoptosis assays in vitro, along with tumor xenografts growth, angiogenesis and invasion in vivo according to both gain-of-function and loss-of-function experiments. Additionally, RPS6KB1 was identified as a novel direct target of miR-195 through proteomic expression profiling combined with bioinformatic target prediction and luciferase reporter assay. Moreover, the re-expression and knockdown of RPS6KB1 could respectively rescue and imitate the effects induced by miR-195. Importantly, RPS6KB1 expression was closely correlated with aggressive progression and poor prognosis in PCa patients as opposed to miR-195. Furthermore, we identified MMP-9, VEGF, BAD and E-cadherin as the downstream effectors of miR-195-RPS6KB1 axis. Conclusion The newly identified miR-195-RPS6KB1 axis partially illustrates the molecular mechanism of PCa progression and represents a novel potential therapeutic target for PCa treatment.

Our previous microarray data showed that microRNA-224 (miR-224) was downregulated in human prostate cancer (PCa) tissues compared with adjacent benign tissues. However, the underlying mechanisms by which miR-224 is involved in PCa remain unclear. In this study, we identified TRIB1 as a target gene of miR-224. Forced expression of miR-224 suppressed PCa cell proliferation, invasion and migration, and promoted cell apoptosis by downregulating TRIB1. Moreover, the expression level of miR-224 in PCa tissues was negatively correlated with that of TRIB1. miR-224 downregulation was frequently found in PCa tissues with metastasis, higher PSA level and clinical stage, whereas TRIB1 upregulation was significantly associated with metastasis. Both miR-224 downregulation and TRIB1 upregulation were significantly associated with poor biochemical recurrence-free survival of patients with PCa. In conclusion, these findings reveal that the aberrant expression of miR-224 and TRIB1 may promote PCa progression and have potentials to serve as novel biomarkers for PCa prognosis.

Clin Invest Med 2008; 31 (1): E8-E15. AbstractObjective: Ki-67 is a proliferation-associated nuclear antigen and is expressed in all cycling cells except for resting cells in the G0-phase. PCNA is an acidic nuclear protein and has been recognized as a histologic marker for the G1/ S phase in the cell cycle. Ki-67and PCNA labeling indices are considered to reflect cell proliferation, particularly, growth fraction. The purpose of this study is to investigate the expression levels of Ki-67 and PCNA in prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and their potential on the early diagnosis of PCa. Methods: Human prostate cancer cell lines LNCaP and PC-3, human normal prostate epithelial cell line HuPEC, tissues from patients with PCa (121 cases) and BPH (45) and 36 normal cases were examined for the expression of Ki-67 and PCNA by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Then, the association of Ki-67 and PCNA expression with clinical grading of PCa was analyzed by immunohistochemistry staining. Results: The ratios of PCNA and Ki-67 expression levels in LNCaP and PC-3 were higher (P<0.05, P<0.001) than that in HuPEC. The two markers were differentially expressed in three tissues and showed increased expression in PCa (P<0.05) and BPH (P<0.05), relative to human normal prostate tissues. Compared with BPH, the ratio of Ki-67 and PCNA expressed in tumour tissue was increased (P<0.05). The increase of Ki-67 was greater than that of PCNA. Expression of the two markers increased after different grading of PCa cases Prostate cancer (PCa) is the second most frequent cause of male cancer-related death in the United States of America (USA) and Western Europe. Its incidence is continuously rising, with over 200 000 new cancers and 35 000~40 000 deaths per year, 1 Carcinogenesis and the mechanisms influencing the progression and prognosis of PCa is a multistep process, involving both genetic insults to epithelial cells and changes in epithelial-stromal interactions. 2 Despite extensive research PCa is not understood.There are two proliferative markers-Ki-67 and proliferating cell nuclear antigen (PCNA). Ki-67 antigen is expressed in proliferative cells throughout the G1, S, G2, and M phases, and provides a reliable index of cellular proliferation 3,4 PCNA is an acidic nuclear protein, expressed mainly in phase S of the cellular cycle. It becomes active, in various tissues par-

Aim: CD147 and MMPs have been demonstrated to be involved in tumor invasion and angiogenesis. The aim of this study was to analyze the clinicopathological significance of CD147, MMP-1, MMP-2 and MMP-9 expression in human prostate cancer (PCa) and to evaluate their involvement in the progression of PCa. Methods: CD147, MMP-1, MMP-2 and MMP-9 expression was assessed in paraffin-embedded specimens collected from 62 cases of PCa and 15 cases of benign prostatic hyperplasia (BPH) by immunohistochemistry. Spearman’s correlation was applied to determine possible relationships between CD147, MMP-1, MMP-2 and MMP-9 expression and PCa. The association of CD147 and MMP-2 protein expression with the clinicopathological characteristics and the prognosis of PCa was subsequently assessed. Results: CD147was expressed in 51/62 (82.3%) PCa patients and in 2/15 (13.3%) BPH cases. MMP-1, MMP-2 and MMP-9 expression was significantly higher in PCa tissue than in BPH tissue. Using Spearman analysis, a significant positive correlation between CD147 and MMP-1, MMP-2 and MMP-9 expression was found (p <0.05). CD147 and MMP-2 expression was correlated with TMN grade and Gleason score. Patients with concurrent expression of CD147+ and MMP-2+ had the lowest survival (p <0.01). Conclusion: The results suggest that concurrent expression of CD147 and MMP may be an important characteristic of PCa which may help in the prediction of PCa progression.

The ability to passivate defects and modulate the interface energy-level alignment (IEA) is key to boost the performance of perovskite solar cells (PSCs). Herein, we report ar obust route that simultaneously allows defect passivation and reduced energy difference between perovskite and hole transport layer (HTL) via the judicious placement of polar chlorine-terminated silane molecules at the interface. Density functional theory (DFT) points to effective passivation of the halide vacancies on perovskite surface by the silane chlorine atoms.A ni ntegrated experimental and DFT study demonstrates that the dipole layer formed by the silane molecules decreases the perovskite work function, imparting an Ohmic character to the perovskite/HTL contact. The corresponding PSCs manifest anearly 20 %increase in power conversion efficiency over pristine devices and am arkedly enhanced device stability.A ss uch, the use of polar molecules to passivate defects and tailor the IEA in PSCs presents apromising platform to advance the performance of PSCs.

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The stability of covalent organic frameworks (COFs) is essential to their applications. However, the common boronate ester-linked COFs are susceptible to attack by nucleophiles (such as water molecules) at the electron-deficient boron sites. To provide an understanding of the hydrolytic stability of the representative boronate ester-linked COF-5 and of the associated hydrolysis mechanisms, density functional theory (DFT) calculations were performed to characterize the hydrolysis reactions of the molecule formed by the condensation of 1,4-phenylenebis(boronic acid) (PBBA) and 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP) monomers; two cases were considered, one dealing with the freestanding molecule and the other with the molecule interacting with COF layers. It was found that the boronate ester (B-O) bond dissociation, which requires one H 2 O molecule, has a relatively high energy barrier of 22.3 kcal mol −1 . However, the presence of an additional H 2 O molecule significantly accelerates hydrolysis by reducing the energy barrier by a factor of 3. Importantly, the hydrolysis of boronate ester bonds situated in a COF environment follows reaction pathways that are different and have increased energy barriers. These results point to an enhanced hydrolytic stability of COF-5 crystals.

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