1,723,755 research outputs found
miR-4723 directly targets Abl kinases in prostate cancer cells.
<p>(A) Profiling of apoptotic genes and, (B) Cell cycle related genes after overexpression of miR-4723 in PC3 cells showing downregulation of Abl1 by miR-4723. (C) Relative mRNA expression of Abl1 gene as assessed by RT-PCR. (D) Schematic representation of the Abl1 and Abl2 3′-UTRs showing the relative positions of putative miR-4723 binding sites. (E) Immunoblots of endogenous Abl1, Abl2 and other miR-4723 targets in PC3 cells transfected as indicated. GAPDH was used a loading control. (F) Abl1 3′ UTR construct encompassing miR-4723 binding sites or the control construct was cotransfected into PC3 cells with miR-4723 or miR-CON and assayed for relative luciferase activity (*p<.05).</p
miR-4723 expression is widely attenuated in prostate cancer.
<p>(A) Quantitative RT-PCR analysis of relative miR-4723 expression levels in laser capture microdissected (LCM) PCa tissues (n = 57) and patient matched adjacent normal regions. Data were normalized to RNU48 control. Table summarizes the relative miR-4723 expression levels in these specimens. (B) Correlation of miR-4723 expression with clinicopathological characteristics of prostate cancer patients including Gleason grade, pathological stage and biochemical recurrence.</p
Clinical significance of miR-4723 expression in prostate cancer.
<p>(A) ROC curve analysis showing the ability of miR-4723 expression to discriminate between malignant and non-malignant prostate tissue samples. (B) Kaplan-Meier survival curves for prostate cancer patients, stratified based on miR-4723 expression (low and high). p value based on log rank test (*p<.05).</p
Overexpression of miR-4723 expression suppresses tumorigenicity of prostate cancer cells.
<p>To evaluate the functional significance of mir-4723 in prostate cancer, miR-4723 precursor was overexpressed in PC3/LNCaP cell lines by transient transfection followed by functional assays (performed 72 hrs post-transfection). (A) Morphological alterations in PC3/LNCaP cells upon miR-4723 expression assessed by phase-contrast microsopy. (B) Cellular viability assay, (C) Colony formation assay, (D) Transwell-migration assay and (E) Invasion assay in PC3/LNCaP cells mock transfected or transfected with miR-CON or miR-4723 (*P<.05).</p
[Veto of H. 4723, R-428]
This veto message from Governor Mark Sanford vetoes H. 4723, R-428, a bill that creates the South Carolina Affordable Housing Study Committee
Block Card 4723 Glenbrier Road
This image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: Ranch houses | 4723 Glenbrier Road (Toledo, Ohio) | Dwelling | Glendale Hills (Toledo, Ohio) | South Toledo Area (Toledo, Ohio
Block Card 4723 286th Street
This image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: Dwelling | 4723 286th Street (Toledo, Ohio) | Bungalow Style | Parkview Addition (Toledo, Ohio) | Point Place (Toledo, Ohio) | North Toledo Area (Toledo, Ohio
Block Card 4723 Cedarhurst Road
This image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: Ranch Style | Dwelling | 4723 Cedarhurst Road (Toledo, Ohio) | Elmhurst Park Addition (Toledo, Ohio) | Deveaux Area (Toledo, Ohio) | West Toledo (Toledo, Ohio
Block Card 4723 283rd Street
This image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: Dwelling | 4723 283rd Street (Toledo, Ohio) | Ranch houses | Parkview Addition (Toledo, Ohio) | Point Place (Toledo, Ohio) | North Toledo Area (Toledo, Ohio
MicroRNA-4723 inhibits prostate cancer growth through inactivation of the Abelson family of nonreceptor protein tyrosine kinases.
The Abelson (c-Abl) proto-oncogene encodes a highly conserved nonreceptor protein tyrosine kinase that plays a role in cell proliferation, differentiation, apoptosis and cell adhesion. c-Abl represents a specific anti-cancer target in prostate cancer as aberrant activity of this kinase has been implicated in the stimulation of prostate cancer growth and progression. However, the mechanism of regulation of c-Abl is not known. Here we report that Abl kinases are regulated by a novel microRNA, miR-4723, in prostate cancer. Expression profiling of miR-4723 expression in a cohort of prostate cancer clinical specimens showed that miR-4723 expression is widely attenuated in prostate cancer. Low miR-4723 expression was significantly correlated with poor survival outcome and our analyses suggest that miR-4723 has significant potential as a disease biomarker for diagnosis and prognosis in prostate cancer. To evaluate the functional significance of decreased miR-4723 expression in prostate cancer, miR-4723 was overexpressed in prostate cancer cell lines followed by functional assays. miR-4723 overexpression led to significant decreases in cell growth, clonability, invasion and migration. Importantly, miR-4723 expression led to dramatic induction of apoptosis in prostate cancer cell lines suggesting that miR-4723 is a pro-apoptotic miRNA regulating prostate carcinogenesis. Analysis of putative miR-4723 targets showed that miR-4723 targets integrin alpha 3 and Methyl CpG binding protein in addition to Abl1 and Abl2 kinases. Further, we found that the expression of Abl kinase is inversely correlated with miR-4723 expression in prostate cancer clinical specimens. Also, Abl1 knockdown partially phenocopies miR-4723 reexpression in prostate cancer cells suggesting that Abl is a functionally relevant target of miR-4723 in prostate cancer. In conclusion, we have identified a novel microRNA that mediates regulation of Abl kinases in prostate cancer. This study suggests that miR-4723 may be an attractive target for therapeutic intervention in prostate cancer
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