Four MicroRNAs Promote Prostate Cell Proliferation with Regulation of PTEN and Its Downstream Signals In Vitro

Abstract

BackgroundPhosphatase and tensin homologue (PTEN), as a tumor suppressor, plays vital roles in tumorigenesis and progression of prostate cancer. However, the mechanisms of PTEN regulation still need further investigation. We here report that a combination of four microRNAs (miR-19b, miR-23b, miR-26a and miR-92a) promotes prostate cell proliferation by regulating PTEN and its downstream signals in vitro.Methodology/Principal FindingsWe found that the four microRNAs (miRNAs) could effectively suppress PTEN expression by directly interacting with its 3’ UTR in prostate epithelial and cancer cells. Under-expression of the four miRNAs by antisense neutralization up-regulates PTEN expression, while overexpression of the four miRNAs accelerates epithelial and prostate cancer cell proliferation. Furthermore, the expression of the four miRNAs could, singly or jointly, alter the expression of the key components in the phosphoinositide 3-kinase (PI3K)/Akt pathway, including PIK3CA, PIK3CD, PIK3R1 and Akt, along with their downstream signal, cyclin D1.ConclusionsThese results suggested that the four miRNAs could promote prostate cancer cell proliferation by co-regulating the expression of PTEN, PI3K/Akt pathway and cyclin D1 in vitro. These findings increase understanding of the molecular mechanisms of prostate carcinogenesis and progression, even provide valuable insights into the diagnosis, prognosis, and rational design of novel therapeutics for prostate cancer.

MiR-92a regulates viability and angiogenesis of endothelial cells under oxidative stress

“…PTEN is the target of certain cellular miRNAs, including miR-19a/b [30], miR-29a [31], miR-214 [32], miR-205 [33] and miR-494 [34], which can directly suppress the expression of PTEN in a post-transcriptional manner. An inverse correlation between PTEN and miR-92 expression has been observed in many human cancer tissues, which typically express low levels of PTEN protein and high levels of miR-92a [19–21]. In the present study, we found that miR-92a overexpression enhanced endothelial cell viability under oxidative stress via augmenting Akt signaling, suggesting a vasculoprotective effect that is likely mediated through a PTEN-dependent mechanism.…”

“…An inverse correlation between the expression levels of PTEN and miR-92 has been reported in many human cancer tissues [19–21]. To investigate whether PTEN is a target of miR-92a, we analyzed PTEN protein levels in mi-RNA transfected HUVEC cells by western blot.…”

“…The level of miR-92a expression is inversely correlated with expression of phosphatase and tensin homolog (PTEN) in many tumor tissues [19–21]. The loss of PTEN leads to activation of Akt, also known as Protein kinase B (PKB), a regulator of endothelial cell apoptosis and angiogenesis [22].…”

Roles of PTEN (Phosphatase and Tensin Homolog) in Gastric Cancer Development and Progression

“…Negative regulators include MKK-4 (mitogen activated protein kinase kinase-4), TGF-β (transforming growth factor beta), NFκB (nuclear factor of kappa light polypeptide gene enhancer in B-cells), transcriptional cofactor c-JUN and oncogene BMI1; these were shown to suppress PTEN expression in several cancer models (Gericke et al, 2006;Lau et al, 2011;Meng et al, 2012). Many miRNAs are also known to impact on PTEN expression and function in both normal and pathological conditions (Tian et al, 2013). Posttranslational modifications such as active site oxidation, acetylation, phosphorylation, and ubiquitination can also regulate PTEN activity (Gericke et al, 2006;Tamguney and Stokoe, 2007).…”

Avaliação dos fatores indutores da transição epitélio-mesenquimal (EMT) na biologia das células endoteliais

“…Durante os últimos anos, o papel dos miRNAs na regulação da EMT e nas vias de sinalização associadas a esse processo têm sido observado em vários contextos de tumores humanos, dentre eles o miR-10b (MA; TERUYA-FELDSTEIN;WEINBERG, 2007), miR26a (DONG et al, 2014TIAN et al, 2013), miR-29 (RU et al, 2012), miR-34 (LIU et al, 2011SIEMENS et al, 2011;XU et al, 2014), miR-let7 (YU et al, 2007), miR-145 (HU et al, 2014) e miR-146a (ZHONG et al, 2010.…”