MicroRNAs (miRNAs) are a class of small noncoding RNAs, which function in posttranscriptional regulation of gene expression. They are powerful regulators of various cellular activities including cell growth, differentiation, development, and apoptosis. They have been linked to many diseases, and currently miRNA-mediated clinical trial has shown promising results for treatment of cancer and viral infection. This review provides an overview and update on miRNAs biogenesis, regulation of miRNAs expression, their biological functions, and role of miRNAs in epigenetics and cell-cell communication. In addition, alteration of miRNAs following exercise, their associationwith diseases, and therapeutic potential will be explained. Finally, miRNA bioinformatics tools and conventional methods for miRNA detection and quantification will be discussed.
Background:
Despite worthy biologic rationale and numerous studies introducing therapeutic
strategies targeting Epidermal Growth Factor Receptor (EGFR), phase III clinical trials have claimed that these
current anti-EGFR agents did not significantly improve overall survival of Gastric Cancer (GC) patients. Therefore,
to discover flawless candidates of anti-EGFR therapy and ideal prognostic markers, innovative studies are
warranted.
Methods:
The aim of this study was to assess the expression profile of EGFR in GC, adjacent non-tumor and
normal gastric tissues by qRT-PCR, investigating the association of EGFR expression with clinicopathological
features, evaluating possible molecular interaction between EGFR and Androgen Receptor (AR), and elucidating
novel prognostic marker using Cox regression model.
Results:
Among 60 GC patients, 70% (42/60) overexpressed EGFR relative to normal gastric tissues. EGFR
overexpression was significantly correlated with the AR overexpression in GC patients. Although EGFR overexpression
was remarkably associated with unfavorable outcomes (HR= 4.067, 95% CI= 1.228-13.467, p= 0.022),
it was not an independent prognostic factor adjusted for other variables. However, we provided evidences that
simultaneous evaluation of EGFR and AR expression, could independently predict the outcome of GC patients
and could use as a precise prognostic marker. Moreover, it was revealed that induction or inhibition of AR
signaling could alter the mRNA expression of EGFR in GC cell lines.
Conclusion:
By targeting AR and EGFR using a potent AR inhibitor such as Enzalutamide, we postulate the
possible crosstalk between EGFR and AR pathways in GC. Moreover, our study provided evidences elucidating
a novel promising marker, simultaneous evaluation of EGFR and AR expression, which could properly predict
prognosis of gastric cancer patients.
Background: It is well-known that Aurora kinase A (AURKA) shows oncogenic properties in various tumor types including gastric cancer (GC). Moreover, previous studies have demonstrated that AURKA has a specific androgen receptor (AR) binding site in its promoter; thus, it could be regulated by AR. Since it has been shown that AR overexpresses in gastric cancer (GC) as a male-predominant tumor, the goal of this study was to evaluate the association between AR and AURKA and its prognostic value in GC patients. Materials and Methods: We assessed the expression profile of AURKA in 60 fresh GC and adjacent non-tumor tissues and 50 normal gastric specimen by qRT-PCR, and investigated the association of AURKA expression with clinicopathological features. Furthermore, we evaluated possible correlation between AURKA and AR to elucidate a novel prognostic marker using Kaplan-Meier method and Cox regression model. Conclusion: Among GC patients, 65% (39/60) overexpressed AURKA relative to normal gastric tissues. AURKA overexpression was significantly correlated with the AR overexpression in GC patients. Although AURKA expression alone was not remarkably associated with poor outcome, we provided some evidence that combined evaluation of AURKA and AR expression could independently predict survival of GC patients adjusted for other variables (HR=1.7, CI=1.314-3.833 p=0.042). Conclusion: These results indicate that AR and AURKA may crosstalk to promote GC progression. Our findings have clinical importance because they suggest simultaneous assessment of AURKA and AR expression as a novel potential prognostic marker.
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