miRNA-29b Suppresses Prostate Cancer Metastasis by Regulating Epithelial–Mesenchymal Transition Signaling

Abstract

Prostate cancer remains the second leading cause of cancer deaths among American men. Early diagnosis increases survival rate in patients; however, treatments for advanced disease are limited to hormone ablation techniques and palliative care. Thus, new methods of treatment are necessary for inhibiting prostate cancer disease progression. Here, we have shown that miRNA-29b (miR-29b) expression was lower in prostate cancer cells (PC3 and LNCaP) as compared with immortalized prostate epithelial cells. Between these two prostate cancer cell lines, metastatic prostate cancer PC3 cells displayed lower expression of miR-29b. We also observed a significant downregulation of miR-29b expression in human prostate cancer tissues as compared with patient-matched nontumor tissues. PC3 cells ectopically expressing miR-29b inhibited wound healing, invasiveness, and failed to colonize in the lungs and liver of severe combined immunodeficient mice after intravenous injection, while PC3 cells expressing a control miRNA displayed metastasis. Epithelial cell marker E-cadherin expression was enhanced miR-29b transfected in prostate cancer cells as compared with cells expressing control miRNA. On the other hand, N-cadherin, Twist, and Snail expression was downregulated in PC3 cells expressing miR-29b. Together these results suggested that miR-29b acts as an antimetastatic miRNA for prostate cancer cells at multiple steps in a metastatic cascade. Therefore, miR-29b could be a potentially new attractive target for therapeutic intervention in prostate cancer.

The role of Snail in prostate cancer

“…51 MicroRNA-29b (miR-29b) is lower in prostate cancer cells and tissue as compared with normal epithelial cells, and its overexpression in PC3 prostate cancer cells decreased Snail, Twist and N-cadherin levels, while E-cadherin levels was increased. 52 LIV-1, a zinc transporter protein has been shown to induce EMT by increasing Snail, MMP-2 and -9 activation which results in shedding of heparin binding-epidermal growth factor (HB-EGF). 53 This leads to constitutive phosphorylation of epidermal growth factor receptor (EGFR) and subsequent ERK signaling leading to increased prostate cancer metastasis to bone and soft tissue.…”

MicroRNA-497 Suppresses Proliferation and Induces Apoptosis in Prostate Cancer Cells

“…Up to now, more than 50 miRNAs are abnormally expressed, leading to alteration in the expression and activity of their targets in PCa, such as miR-21, miR-320, miR-29b and miR34c (Ribas et al, 2009;Hagman et al, 2010;Hsieh et al, 2012;Ru et al, 2012 all prostate carcinoma samples compared with the BPH samples (Porkka et al, 2007;Watahiki et al, 2011). Several studies showed that the potential functions of miR-497 in human breast cancer (Li et al, 2011;Shen et al, 2012), neuroblastoma (Yadav et al, 2011), cervical cancer (Zheng et al, 2012), gastric cancer (Zhu et al, 2012) and colorectal cancer (Guo et al, 2012).…”

microRNA-29b: an Emerging Player in Human Cancer

“…In accord with these data, miR-29b directly targets site in the 3'UTR of snail to inhibit tumor metastasis in prostate cancer cells. Consistently, exogenous expression of miR-29b inhibits Mcl-1 and MMP-2 protein expression, and affects metastatic cascade including tumor invasion, motility, cellular survival, and proliferation (Ru et al, 2012). Tiam1, overexpressed in CRC, was validated as a target of miR-29b by binding directly in the Tiam1 3'UTR.…”