Identification of miRs-143 and -145 that Is Associated with Bone Metastasis of Prostate Cancer and Involved in the Regulation of EMT

Peng, Xinsheng; Guo, Wei; Tiejian, Liu; Wang, Xi; Tu, Xiang-An; Xiong, Dafu; Chen, Song; Lai, Yingrong; Du, Hong; Chen, Guangfu; Liu, Guanglin; Tang, Yubo; Huang, Shuai; Zou, Xuenong

doi:10.1371/journal.pone.0020341

Cited by 205 publications

(201 citation statements)

References 79 publications

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“…5). miR-143 has been shown to have an antimetastatic effect and is downregulated in several cancers (Takagi et al 2009, Kent et al 2010, Peng et al 2011. miR-143 and miR-145 are often cotranscribed and are usually investigated together as tumour suppressors (Kent et al 2014).…”

Section: :9mentioning

confidence: 99%

“…miR-143 and miR-145 are often cotranscribed and are usually investigated together as tumour suppressors (Kent et al 2014). In prostate cancer, over-expression of miR-143 and -145 reduces migration and invasion in vitro and tumour development and bone invasion in vivo (Peng et al 2011). Furthermore, lower expression of miR-143 and miR-145 in primary prostate cancers was significantly associated with tumour progression and the development of bone metastases (Peng et al 2011).…”

Section: :9mentioning

confidence: 99%

“…In prostate cancer, over-expression of miR-143 and -145 reduces migration and invasion in vitro and tumour development and bone invasion in vivo (Peng et al 2011). Furthermore, lower expression of miR-143 and miR-145 in primary prostate cancers was significantly associated with tumour progression and the development of bone metastases (Peng et al 2011). Interestingly, deregulation of miR-143 and miR-145 has not been seen in LN metastasis compared with primary prostate tumours (Spahn et al 2010).…”

Section: :9mentioning

confidence: 99%

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MicroRNAs associated with small bowel neuroendocrine tumours and their metastases

Miller¹,

Frampton²,

Malczewska³

et al. 2016

Endocrine-Related Cancer

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Novel molecular analytes are needed in small bowel neuroendocrine tumours (SBNETs) to better determine disease aggressiveness and predict treatment response. In this study, we aimed to profile the global miRNome of SBNETs, and identify microRNAs (miRNAs) involved in tumour progression for use as potential biomarkers. Two independent miRNA profiling experiments were performed (n = 90), including primary SBNETs (n = 28), adjacent normal small bowel (NSB; n = 14), matched lymph node (LN) metastases (n = 24), normal LNs (n = 7), normal liver (n = 2) and liver metastases (n = 15). We then evaluated potentially targeted genes by performing integrated computational analyses. We discovered 39 miRNAs significantly deregulated in SBNETs compared with adjacent NSB. The most upregulated (miR-204-5p, miR-7-5p and miR-375) were confirmed by qRT-PCR. Two miRNAs (miR-1 and miR-143-3p) were significantly downregulated in LN and liver metastases compared with primary tumours. Furthermore, we identified upregulated gene targets for miR-1 and miR-143-3p in an existing SBNET dataset, which could contribute to disease progression, and show that these miRNAs directly regulate FOSB and NUAK2 oncogenes. Our study represents the largest global miRNA profiling of SBNETs using matched primary tumour and metastatic samples. We revealed novel miRNAs deregulated during SBNET disease progression, and important miRNA-mRNA interactions. These miRNAs have the potential to act as biomarkers for patient stratification and may also be able to guide treatment decisions. Further experiments to define molecular mechanisms and validate these miRNAs in larger tissue cohorts and in biofluids are now warranted.

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Section: :9mentioning

confidence: 99%

Section: :9mentioning

confidence: 99%

Section: :9mentioning

confidence: 99%

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MicroRNAs associated with small bowel neuroendocrine tumours and their metastases

Miller¹,

Frampton²,

Malczewska³

et al. 2016

Endocrine-Related Cancer

View full text Add to dashboard Cite

show abstract

“…A separate study found that both miR-143 and miR-145 decreased in bone metastatic samples compared with primary tumors, and ectopic expression reduced migration, invasion and bone metastasis. 71 …”

Section: Tumor-intrinsic Mirna Regulation Of Bone Metastasismentioning

confidence: 99%

MicroRNAs as regulators of bone homeostasis and bone metastasis

Ell

Kang

2014

Bonekey Reports

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MicroRNAs (miRNAs) are short, endogenous RNAs that have essential roles in regulating gene expression through the disruption of target genes. The miRNA-induced suppression can occur through Argonaute-mediated cleavage of target mRNAs or by translational inhibition. System-wide studies have underscored the integral role that miRNAs play in regulating the expression of essential genes within bone marrow stromal cells. The miRNA expression has been shown to enhance or inhibit cell differentiation and activity, and elucidating miRNA targets within bone marrow cells has revealed novel regulations during normal bone development. Importantly, multiple studies have shown that miRNA misexpression mediates the progression of bone-related pathologies, including osteopetrosis and osteoporosis, as well as the development and progression of osteosarcoma. Furthermore, recent studies have detailed the capacity for miRNAs to influence bone metastasis from a number of primary carcinomas. Taken together, these findings reveal the significant clinical potential for miRNAs to regulate bone homeostasis, as well as to mediate bone-related pathologies.BoneKEy Reports 3, Article number: 549 (2014) | doi:10.1038/bonekey.2014.44 MiRNA Biogenesis and FunctionThe past decade has seen a torrent of novel research into the post-translational regulation of genes via microRNA-mediated suppression. The microRNAs (miRNAs) are a class of B22-nucleotide-long RNAs that repress gene expression through complementary binding to sites in the 3 0 -untranslated region (UTR) of target mRNAs. 1 Mature miRNAs are generated by the sequential cleavage of longer precursor transcripts, or pri-miRNAs, that are typically transcribed from intragenic or intergenic regions by RNA polymerase II. 2 The initial cleavage step, mediated by Drosha and the DGCR8 complex, occurs in the nucleus and produces a shortened (70-100 nucleotides) pre-miRNA hairpin. Pre-miRNAs are exported from the nucleus by Exportin 5, followed by a second cleavage by the ribonuclease Dicer that produces a double-stranded, B18-25-nucleotide-long mature miRNA. One miRNA strand will then combine with Argonaute (AGO2) proteins to produce an RNAinduced silencing complex, allowing for directed pairing with target mRNAs. 1

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“…30 In the androgen-insensitive PC-3 prostate cancer cell line, ectopic expression of miR-143 and miR-145 prevented EMT, reducing the migratory capacities of these cells in vitro and their propensity to metastasise to bone in vivo. 31 Further, miR-145 attenuates EMT and invasion of PC-3 cells through repression of the oncogenic protein HEF1. 32 The low miR-143 and miR-145 expression levels in prostate tumours and in bone metastasis biopsies were negatively correlated to bone relapses, free prostate-specific antigen level and the Gleason score, suggesting that these miRNAs could be used as biomarkers to discriminate different stages of prostate carcinomas and predict bone metastasis relapse.…”

Section: Mirnas In Primary Carcinomas Are Potential Predictive Factormentioning

confidence: 99%

Tumour-derived miRNAs and bone metastasis

Croset

Kan

Clézardin³

2015

BoneKEy Reports

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Skeletal metastases are complications of epithelial cancers, among which breast, prostate and lung carcinomas are the most osteotropic. In primary tumours, a subset of cancer cells undergoes epithelial-mesenchymal transition, acquires mobility to migrate into the surrounding stroma and seeds at distant sites to grow. The specific development of bone metastasis requires the recruitment of circulating tumour cells in the bone marrow, their adaptation to survive in the surrounding microenvironment where they alter the functions of osteoclasts and osteoblasts, and hijack signals coming from the bone matrix. Each of the molecular pathways underlining these steps is regulated by multiple factors, through the tight control of genes expressed by cancer cells interacting with cells from the bone microenvironment. In this context, miRNAs can act as master regulators of gene expression to control multiple aspects of bone metastasis formation, including cancer cell escape from the primary tumour site, cancer cell dissemination to bone and invasion of the bone marrow, as well as secondary outgrowth and tumour-stroma cell interactions. In the clinic, specific miRNA signatures have been identified in osteotropic cancer cells, raising the possibility that miRNAs could be used as biomarkers of bone metastasis. The regulatory activity of miRNAs in the bone microenvironment also suggests that miRNAs could be promising therapeutic targets.

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Identification of miRs-143 and -145 that Is Associated with Bone Metastasis of Prostate Cancer and Involved in the Regulation of EMT

Cited by 205 publications

References 79 publications

MicroRNAs associated with small bowel neuroendocrine tumours and their metastases

MicroRNAs associated with small bowel neuroendocrine tumours and their metastases

MicroRNAs as regulators of bone homeostasis and bone metastasis

Tumour-derived miRNAs and bone metastasis

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