Role of miRNALet-7and Its Major Targets in Prostate Cancer

Abstract

Prostate cancer is worldwide the sixth leading cause of cancer related death in men thus early detection and successful treatment are still of major interest. The commonly performed screening of the prostate-specific antigen (PSA) is controversially discussed, as in many patients the prostate-specific antigen levels are chronically elevated in the absence of cancer. Due to the unsatisfying efficiency of available prostate cancer screening markers and the current treatment outcome of the aggressive hormone refractory prostate cancer, the evaluation of novel molecular markers and targets is considered an issue of high importance. MicroRNAs are relatively stable in body fluids orchestrating simultaneously the expression of many genes. These molecules are currently discussed to bear a greater diagnostic potential than protein-coding genes, being additionally promising therapeutic drugs and/or targets. Herein we review the potential impact of the microRNA let-7 family on prostate cancer and show how deregulation of several of its target genes could influence the cellular equilibrium in the prostate gland, promoting cancer development as they do in a variety of other human malignant neoplasias.

Down-regulation of let-7 microRNA increased K-ras expression in lung damage induced by radon

“…More recently, Shen et al (2015) reported that the single-nucleotide polymorphism in the promoter region of let-7 family is strongly associated with susceptibility to lung adenocarcinoma in Chinese individuals, especially in females who are more than 60 years old. In addition, aberrant expression of let-7 has also been observed in many other human malignancies (Ma et al, 2014), with a distinct expression pattern in cancer development (Boyerinas et al, 2010;Wagner et al, 2014). It has been reported that the let-7 family expression is closely associated with pathologic classification in lung cancer (Esquela-Kerscher et al, 2008;Kumar et al, 2008;Trang et al, 2011).…”

Let-7 Suppresses B Cell Activation through Restricting the Availability of Necessary Nutrients

“…Moreover, a double-negative feedback loop between let-7 and c-Myc has been well established (Kolenda et al, 2014;Sampson et al, 2007;Wagner et al, 2014;Wang et al, 2012). Therefore, to further investigate the mechanism of the let-7adf cluster in regulating the uptake and utilization of glutamine in activated B cells, we examined the expression of c-Myc in the let-7adf cluster KO B cells.…”

Protease-activated Receptor-2 (PAR-2)-mediated Nf-κB Activation Suppresses Inflammation-associated Tumor Suppressor MicroRNAs in Oral Squamous Cell Carcinoma

“…Here, we demonstrate that PAR-2 activation suppresses three antiinflammatory microRNAs: let-7d, miR-23b, and miR-200c. let-7d has been shown to target pro-inflammatory mRNAs encoding IL6, IL13, and TLR4 (47)(48)(49). miR-23b limits tissue inflammation via suppression of Nf-B activation and inflammatory cytokine expression by targeting TAB2, TAB3, and IKK␣ (50).…”