MicroRNA-296-5p (miR-296-5p) functions as a tumor suppressor in prostate cancer by directly targeting Pin1

Lee, Kuen-Haur; Lin, Fengyi; Hsu, Tai-I; Lin, Jen-Tai; Guo, Jing; Tsai, Chen Hsun; Lee, Yu Cheng; Lee, Yu Chieh; Chen, Chi Long; Hsiao, Michael; Lu, Pei Jung

doi:10.1016/j.bbamcr.2014.06.001

Cited by 93 publications

(75 citation statements)

References 52 publications

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“…Down-regulation of miR-296 has been reported in many human cancers[31–34]. It typically occurs in later phases of carcinogenesis and is associated with the progression to aggressive disease[33,34].…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profile of the Clinically Aggressive Micropapillary Variant of Bladder Cancer

et al. 2016

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Background Progression of conventional urothelial carcinoma of the bladder to a tumor with unique microscopic features referred to as micropapillary carcinoma is coupled with aggressive clinical behavior signified by a high propensity for metastasis to regional lymph nodes and distant organs resulting in shorter survival. Objective To analyze the expression profile of micropapillary cancer and define its molecular features relevant to clinical behavior. Design, setting, and participants We retrospectively identified 43 patients with micropapillary bladder cancers and a reference set of 89 patients with conventional urothelial carcinomas and performed whole-genome expression mRNA profiling. Outcome, measurements and statistical analysis The tumors were segregated into distinct groups according to hierarchical clustering analyses. In addition, the tumors were classified according to luminal, p53-like, and basal categories using previously described algorithm. We applied IPA and GSEA for pathway analyses. Cox proportional hazards models and Kaplan-Meier methods were used to assess the relationship between survival and molecular subtypes. The expression profile of micropapillary cancer was validated for selected markers by immunohistochemistry on parallel tissue microarrays. Results We show that the striking features of micropapillary cancer are downregulation of miR-296 and activation of chromatin-remodeling complex RUVBL1. In contrast to conventional urothelial carcinomas which, based on their expression, can be equally divided into luminal and basal subtypes, micropapillary cancer is almost exclusively luminal, displaying enrichment of active PPARγ and suppression of p63 target genes. As with conventional luminal urothelial carcinomas, a subset of micropapillary cancers exhibit activation of wild-type p53 downstream genes and represent the most aggressive molecular subtype of the disease, with the shortest survival. Conclusions Micropapillary cancer evolves through the luminal pathway and is characterized by the activation of miR-296 and RUVBL1 target genes. Limitations The involvement of miR-296 and RUVBL1 in the development of micropapillary bladder cancer was identified by the analyses of correlative associations of genome expression profiles and requires mechanistic validation. Patient summary Our observations have important implications for prognosis and for possible future development of more effective therapies for micropapillary bladder cancer.

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Section: Discussionmentioning

confidence: 99%

Gene Expression Profile of the Clinically Aggressive Micropapillary Variant of Bladder Cancer

et al. 2016

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“…Recently, we found that Pin1 may be regulated either by miRNA or post-translational modification by Aurora A (Table 1). 11,21 In the following sections, we will describe specific molecular interactions that taken together comprise the landscape of Pin1 activity in cell cycle progression ( Figure 1). …”

Section: Pin1 Regulation Of the Cell Cyclementioning

confidence: 99%

Landscape of Pin1 in the cell cycle

Lin

Lee

et al. 2015

Exp Biol Med (Maywood)

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Pin1 is a peptidyl-prolyl isomerase which plays a critical role in many diseases including cancer and Alzheimer's disease. The essential role of Pin1 is to affect stability, localization or function of phosphoproteins by catalyzing structural changes. Among the collection of Pin1 substrates, many have been shown to be involved in regulating cell cycle progression. The cell cycle disorder caused by dysregulation of these substrates is believed to be a common phenomenon in cancer. A number of recent studies have revealed possible functions of several important Pin1-binding cell cycle regulators. Investigating the involvement of Pin1 in the cell cycle may assist in the development of future cancer therapeutics. In this review, we summarize current knowledge regarding the network of Pin1 substrates and Pin1 regulators in cell cycle progression. In G1/S progression, cyclin D1, RB, p53, p27, and cyclin E are all well-known cell cycle regulators that are modulated by Pin1. During G2/M transition, our lab has shown that Aurora A suppresses Pin1 activity through phosphorylation at Ser16 and cooperates with hBora to modulate G2/M transition. We conclude that Pin1 may be thought of as a molecular timer which modulates cell cycle progression networks.

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“…Recently, a bioinformatics analysis revealed that miR-296-5p has a conserved binding site in the Pin1 3 0 -untranslated region (UTR) directly interacting with the 3 0 -UTR of Pin1 mRNA. Moreover, miR-296-5p expression was found to be inversely correlated with Pin1 expression in PCa cell lines and PCa tissues, and the restoration of miR-296-5p or the knockdown of Pin1 had the same effect on the inhibition of the ability of cell proliferation and anchorage-independent growth of PCa cell lines [134]. miR-18a, which belongs to the miR17-92 cluster, is upregulated in PCa.…”

Section: Mirnas As Therapeutic Tool In Prostate Cancermentioning

confidence: 98%

Gene interference strategies as a new tool for the treatment of prostate cancer

et al. 2015

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Prostate cancer (PCa) is one of the most common cancer in men. It affects older men and the incidence increases with age; the median age at diagnosis is 67 years. The diagnosis of PCa is essentially based on three tools: digital rectal exam, serum concentration of prostate specific antigen, and transrectal ultrasound-guided biopsy. Currently, the therapeutic treatments of this cancer are different and range from the prostatectomy to hormonal therapy, to radiation therapy, to immunotherapy, and to chemotherapy. However, additional efforts are required in order to find new weapons for the treatment of metastatic setting of disease. The purpose of this review is to highlight new therapeutic strategies based on gene interference; in fact, numerous siRNA and miRNA in the therapeutic treatment of PCa are reported below.

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MicroRNA-296-5p (miR-296-5p) functions as a tumor suppressor in prostate cancer by directly targeting Pin1

Cited by 93 publications

References 52 publications

Gene Expression Profile of the Clinically Aggressive Micropapillary Variant of Bladder Cancer

Gene Expression Profile of the Clinically Aggressive Micropapillary Variant of Bladder Cancer

Landscape of Pin1 in the cell cycle

Gene interference strategies as a new tool for the treatment of prostate cancer

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