The SOX4/miR-17-92/RB1 Axis Promotes Prostate Cancer Progression.

Although androgen-deprivation treatment (ADT) is the main treatment for advanced prostate cancer (PCa), it eventually fails. This failure invariably leads to castration-resistant prostate cancer (CRPC) and the development of the neuroendocrine (NE) phenotype. The molecular basis for PCa progression remains unclear. Previously, we and others have demonstrated that the sex-determining region Y-box 4 (SOX4) gene, a critical developmental transcription factor, is overexpressed and associated with poor prognosis in PCa patients. In this study, we show that SOX4 expression is associated with PCa progression and the development of the NE phenotype in androgen deprivation conditions. High-throughput microRNA profiling and bioinformatics analyses suggest that SOX4 may target the miR-17-92 cluster. SOX4 transcriptionally upregulates miR-17-92 cluster expression in PCa cells. SOX4-induced PCa cell proliferation, migration, and invasion are also mediated by miR-17-92 cluster members. Furthermore, RB1 is a target gene of miR-17-92 cluster. We found that SOX4 downregulates RB1 protein expression by upregulating the miR-17-92 expression. In addition, SOX4-knockdown restrains NE phenotype and PCa cell proliferation. Clinically, the overexpression of miR-17-92 members is shown to be positively correlated with SOX4 expression in PCa patients, whereas RB1 expression is negatively correlated with SOX4 expression in patients with the aggressive PCa phenotype. Collectively, we propose a novel model of a SOX4/miR-17-92/RB1 axis that may exist to promote PCa progression.

CUL4B/miR-33b/C-MYC axis promotes prostate cancer progression.

BACKGROUND: Cullin 4B (CUL4B), a scaffold protein that assembles CRL4B ubiquitin ligase complexes, is overexpressed in many types of solid tumors and contributes to epigenetic silencing of tumor suppressors. However, its clinical significance and underlying molecular mechanisms in prostate cancer (PCa) remain unknown. METHODS: The clinical significance of CUL4B in PCa was characterized by in silico method. RT-qPCR and Western blot were used to study the transcript and protein expression levels of CUL4B and C-MYC. Bioinformatics tools, chromatin immunoprecipitation (ChIP) and luciferase reporter assay were utilized to identify and characterize the microRNAs (miRNAs) regulated by CUL4B. The biological function of CUL4B and miR-33b-5p was evaluated by MTS, transwell, and wound healing assays, accordingly. RESULTS: CUL4B is significantly overexpressed in PCa tissues compared with benign prostatic tissues and its overexpression is correlated with poor prognosis. CUL4B promotes proliferation and aggressiveness of PCa cells in vitro. Mechanistically, we demonstrate that CUL4B upregulates the expression of C-MYC at post-transcriptional level through epigenetic silencing of miR-33b-5p. Importantly, CUL4B-induced oncogenic activity in PCa by targeting C-MYC is repressed by miR-33b-5p. CONCLUSIONS: Our results suggested a novel CUL4B/miR-33b/C-MYC axis implicated in PCa cell growth and progression. This might provide novel insight into how CUL4B contributed to PCa aggressiveness and progression.

Lipofuscin- and melanin-related fundus autofluorescence in patients with submacular idiopathic choroidal neovascularization.

PURPOSE: To compare melanin-related near-infrared fundus autofluorescence (NIA; excitation 787 nm, emission> 800 nm) with lipofuscin-related fundus autofluorescence (FAF; excitation 488 nm, emission > 500 nm) in patients with idiopathic choroidal neovascularization (ICNV). METHODS: FAF, NIA, fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were obtained using a confocal scanning laser Ophthalmoscope HRA2 (Heidelberg Retina Angiograph 2) in 18 eyes of 18 patients with ICNV. RESULTS: Eighteen eyes had classic CNV, and autofluorescence imaging showed hypoautofluorescence at the site of CNV. A well-defined hyperautofluorescent ring was detected surrounding the CNV in all 18 eyes with NIA imaging. In our sample, the FAF patterns around the CNV were classified as normal (n=1, 5.56%), well-defined hyperautofluorescent ring (n=7, 38.89%), or ill-defined hyperautofluorescent ring (n=10, 55.56%). CONCLUSION: The patterns of FAF and NIA indicated different involvement of lipofuscin and melanin in the pathophysiological process of ICNV. Compared to FAF imaging, NIA imaging appears to be a superior noninvasive method for in vivo visualization of retinal pigment epithelium (RPE) abnormalities in ICNV patients.

Characteristics of fundus autofluorescence in cystoid macular edema.

BACKGROUND: Fundus autofluorescence (FAF) imaging is a fast and noninvasive technique developed over the last decade. The authors utilized fluorescent properties of lipofuscin to study the health and viability of the retinal pigment epithelium (RPE)-photoreceptor complex. Observing the intensity and distribution of FAF of various retinal diseases is helpful for ascertaining diagnosis and evaluating prognosis. In this study, we described the FAF characteristics of cystoid macular edema (CME). METHODS: Sixty-two patients (70 eyes) with CME were subjected to FAF and fundus fluorescein angiography (FFA) by a confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph 2 (HRA2)). Characteristics of FAF images were compared with FFA images. RESULTS: FAF intensity in normal subjects was highest at the posterior pole and dipped at the fovea. All cases of CME showed fluorescein dye accumulated into honeycomb-like spaces in macular and formated a typical petaloid pattern or atypical petaloid pattern in the late phases of the angiography. Sixty-one eyes with CME on FAF images showed mild or moderate hyperautofluorescence petaloid pattern in fovea, the FAF patterns of these CME was perfectly corresponding with shape in their FFA images; nine eyes with CME secondary to exudative age related macular degeneration (AMD) showed expansion of the hypoautofluorescence without petaloid pattern in macula. CONCLUSION: FAF imaging can be used as a new rapid, non-invasive and ancillary technique in the diagnosis of the majority of CME, except for AMD and small part of other fundus diseases.

Downregulation of Nogo-A expression of oligodendrocytes in vitro with antisense oligodeoxynucleotides.

PURPOSE: To investigate the effect of antisense oligonucleotides (ODN) to Nogo-A mRNA expression in oligodendrocytes and to establish the base for further research of repair of optic nerve injury. METHOD: (1) Oligodendrocytes were obtained by inoculating the optic nerve of newborn (2 days) rats and were identified with galactocerebroside(GC) antibody immunocytochemical stain. (2) In order to observe the effects of antisense ODN on cultured cells, we set up five groups, including the groups of three concentration of antisense Nogo-A ODN (2 microM, 5 microM, 10 microM), a group with the random sequence added to the medium and the control group. Reverse transcription-polymerase chain reaction (RT-PCR) was adopted to study the effects of ODN on the expression of Nogo-A in oligodendrocytes. RESULTS: (1) Three days after inoculation, a few of round or fusiform shape cells migrated from optic nerve tissue; About 11 days later, the coverlips were completely covered by the cells; The cells identified with GC antibody immunocytochemical stain were positive cells. (2) The result of RT-PCR study showed that antisense Nogo-A ODN could significantly and specifically inhibit the expression of Nogo-A after 24 hours (P < 0.01). Random sequence has no effect on Nogo-A expression. CONCLUSION: Antisense Nogo-A ODN can effectively and specifically inhibit the expression of Nogo-A.