Expression of microRNAs and protein‐coding genes associated with perineural invasion in prostate cancer

Prueitt, Robyn L.; Yi, Ming; Hudson, Robert S.; Wallace, Tiffany A.; Howe, Tiffany M.; Yfantis, Harris G.; Lee, Dong Hoon; Stephens, Robert M.; Liu, Chang Gong; Calin, George A.; Croce, Carlo M.; Ambs, Stefan

doi:10.1002/pros.20786

Cited by 130 publications

(111 citation statements)

References 51 publications

Supporting

Mentioning

108

Contrasting

Order By: Relevance

“…For example, hsa-let-7f was found to be significantly up-regulated in breast cancer (Yan et al, 2008), and hsa-miR-224 was found to be significantly up-regulated in prostate and thyroid cancer (Prueitt et al, 2008;Nikiforova et al, 2008). This might point out the presence of 'common' pathways that are used by cancers in different organ tissues.…”

Section: Discussionmentioning

confidence: 99%

Three dysregulated miRNAs control kallikrein 10 expression and cell proliferation in ovarian cancer

et al. 2010

View full text Add to dashboard Cite

BACKGROUND: Kallikrein-related peptidases (KLKs) are a family of serine proteases that have been shown to be dysregulated in several malignancies including ovarian cancer. The control of kallikrein genes and their physiological function in cancer is not well understood. We hypothesized that microRNAs (miRNAs) represent a novel mechanism for post-transcriptional control of KLK expression in cancer. METHODS: We first analysed miRNA expression in ovarian cancer in silico. A total of 98 miRNAs were reported to have altered expression in ovarian cancer. Three of these miRNAs were predicted to target KLK10. We experimentally verified the predicted miR -KLK10 interaction using two independent techniques, a luciferase assay with a construct containing the KLK10 3 0 untranslated region (UTR), pMIR -KLK10, and measuring KLK10 protein levels after transfection with miRNA. RESULTS: When we co-transfected cells with pMIR -KLK10 and either let-7f, miR-224, or mR-516a, we saw decreased luciferase signal, suggesting that these miRNAs can target KLK10. We then examined the effect of these three miRNAs on KLK10 protein expression and cell growth. Transfection of all miRNAs, let-7f, miR-224, and miR-516a led to a decrease in protein expression and cellular growth. This effect was shown to be dose dependent. The KLK10 protein levels were partially restored by co-transfecting let-7f and its inhibitor. In addition, there was a slight decrease in KLK10 mRNA expression after transfection with let-7f. CONCLUSIONS: Our results confirm that KLKs can be targeted by more than one miRNA. Increased expression of certain miRNAs in ovarian cancer can lead to decreased KLK protein expression and subsequently have a negative effect on cell proliferation. This dose-dependent effect suggests that a 'tweaking' or 'fine-tuning' mechanism exists in which the expression of one KLK can be controlled by multiple miRNAs. These data together suggest that miRNA may be used as potential therapeutic options and further studies are required.

show abstract

Section: Discussionmentioning

confidence: 99%

Three dysregulated miRNAs control kallikrein 10 expression and cell proliferation in ovarian cancer

et al. 2010

View full text Add to dashboard Cite

show abstract

“…76 Furthermore, enforced expression of miR125b promoted tumor growth through mediation of a broad attenuation of the intrinsic apoptosis pathway by targeting P53, PUMA and BAK1. 23 MiR-125b was also found to stimulate androgen-independent growth of prostate cancer cells in vitro.…”

Section: Mir-125b In Solid Tumors-oncomir or Tumor Suppressor?mentioning

confidence: 99%

MiR-125 in normal and malignant hematopoiesis

et al. 2012

View full text Add to dashboard Cite

MiR-125 is a highly conserved microRNA throughout many different species from nematode to humans. In humans, there are three homologs (hsa-miR-125b-1, hsa-miR-125b-2 and hsa-miR-125a). Here we review a recent research on the role of miR-125 in normal and malignant hematopoietic cells. Its high expression in hematopoietic stem cells (HSCs) enhances self-renewal and survival. Its expression in specific subtypes of myeloid and lymphoid leukemias provides resistance to apoptosis and blocks further differentiation. A direct oncogenic role in the hematopoietic system has recently been demonstrated by several mouse models. Targets of miR-125b include key proteins regulating apoptosis, innate immunity, inflammation and hematopoietic differentiation.

show abstract

“…Nonetheless, other miRNA species affected by Src transformation, including miR-218 and miR-224, may also have important roles in cancer progression (Murakami et al, 2006;Zanette et al, 2007;Guo et al, 2008;Ladeiro et al, 2008;Li et al, 2008;Nikiforova et al, 2008;Prueitt et al, 2008;Wang et al, 2008b;Schembri et al, 2009;Wang and Lee, 2009). Indeed, our results show that Src induces miR-224 expression to promote nonanchored growth of transformed cells, providing a possible explanation for the increased expression of miR-224 observed in a variety of tumors (Murakami et al, 2006;Guo et al, 2008;Ladeiro et al, 2008;Li et al, 2008;Nikiforova et al, 2008;Prueitt et al, 2008;Wang et al, 2008b). Valiunas et al (2005b) have shown that RNA molecules of the size of miRNA can transfer between cells through gap junction channels, particularly through channels formed by connexin 43.…”

Section: % Controlsmentioning

confidence: 99%

Regulation of miRNA expression by Src and contact normalization: effects on nonanchored cell growth and migration

Shen

Ichikawa³

et al. 2009

Oncogene

View full text Add to dashboard Cite

Transformation by the Src tyrosine kinase (Src) promotes nonanchored cell growth and migration. However, nontransformed cells can force Src-transformed cells to assume a normal morphology and phenotype by a process called 'contact normalization'. It has become clear that microRNA (miRNA) can affect tumorigenesis by targeting gene products that direct cell growth and migration. However, the roles of miRNA in Src transformation or contact normalization have not yet been reported. We examined the expression of 95 miRNAs and found 9 of them significantly affected by Src. In this study, we report that miR-218 and miR-224 were most significantly induced by Src, but not affected by contact normalization. In contrast, miR-126 was most significantly suppressed by Src and was induced by contact normalization in transformed cells. Mir-126 targets Crk, a component of the focal adhesion network that participates in events required for tumor cell migration. Accordingly, we show that miR-126 expression correlates inversely with Crk levels, motility and the invasive potential of human mammary carcinoma cells. Moreover, we show that miR-224 expression promotes nonanchored growth of nontransformed cells. These data reveal novel insights into how Src regulates miRNA expression to promote hallmarks of tumor cell growth and invasion, and how nontransformed cells can affect miRNA expression in adjacent tumor cells to inhibit this process.

show abstract

Expression of microRNAs and protein‐coding genes associated with perineural invasion in prostate cancer

Abstract: BACKGROUND-Perineural invasion (PNI) is the dominant pathway for local invasion in prostate cancer. To date, only few studies have investigated the molecular differences between prostate tumors with PNI and those without it.

Cited by 130 publications

References 51 publications

Three dysregulated miRNAs control kallikrein 10 expression and cell proliferation in ovarian cancer

Three dysregulated miRNAs control kallikrein 10 expression and cell proliferation in ovarian cancer

MiR-125 in normal and malignant hematopoiesis

Regulation of miRNA expression by Src and contact normalization: effects on nonanchored cell growth and migration

Contact Info

Product

Resources

About