Down-Regulation of miR-183 Promotes Migration and Invasion of Osteosarcoma by Targeting Ezrin

Zhu, Junfeng; Feng, Yupeng; Ke, Zunfu; Yang, Zheng; Zhou, Jing; Huang, Xiaorong; Wang, Liantang

doi:10.1016/j.ajpath.2012.02.023

Cited by 136 publications

(110 citation statements)

References 51 publications

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“…It was demonstrated that miR-183 targets ezrin, an intermediate between the plasma membrane and the actin cytoskeleton involved, together with radixin, in epithelial cell morphogenesis and adhesion [75], and may play a central role in the regulation of migration and metastasis in breast cancer [76], osteosarcoma [77] and lung cancer [78]. miR-183 is markedly down-regulated in osteosarcoma cells and tissues compared with matching normal bone tissues and its expression levels significantly correlated with lung metastasis as well as with local recurrence of osteosarcoma [77].…”

Section: Mirnas and Metastasismentioning

confidence: 99%

microRNA: New Players in Metastatic Process

Triulzi¹,

Iorio²,

Tagliabue³

et al. 2013

Oncogene and Cancer - From Bench to Clinic

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Section: Mirnas and Metastasismentioning

confidence: 99%

microRNA: New Players in Metastatic Process

Triulzi¹,

Iorio²,

Tagliabue³

et al. 2013

Oncogene and Cancer - From Bench to Clinic

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“…41 MiR-183 and miR-143, which target Ezrin and MMP-13, respectively, can similarly inhibit osteosarcoma migration and invasion. 42,43 Importantly, ectopic expression of miR-143 was able to suppress lung metastasis in a mouse model of human osteosarcoma. 43 Conversely, miR-27a enhanced migration and invasion in vitro while simultaneously increasing pulmonary and bone metastasis after intravenous inoculation.…”

Section: Mirna Expression Influences Growth and Progression Of Osteosmentioning

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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“…34,35 Given the profound effect that regulated miRNA expression has on bone marrow cell differentiation and activity, it is perhaps not surprising that misregulation of miRNAs has also been linked to a number of bone-related pathologies, including miRNAs as biomarkers for bone metastasis progression A Aleč ković and Y Kang [36][37][38] and osteosarcoma. [39][40][41][42][43] Importantly, misregulated miRNAs have been proposed as potential biomarkers of the specific bone-related diseases as they may accurately reflect the disease state of the bone. Because osteoporosis is caused by an imbalance between bone formation and resorption, misregulated bone marrow miRNAs represent promising indicators of assessment of bone fragility and provide potential therapeutic options to restore homeostasis.…”

Section: Mirna Regulation In Bone Homeostasismentioning

confidence: 99%

Bone marrow stroma-derived miRNAs as regulators, biomarkers and therapeutic targets of bone metastasis

Alečković

Kang

2015

BoneKEy Reports

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MicroRNAs (miRNAs) are short, endogenous RNA molecules that have essential roles in regulating gene expression. They control numerous physiological and cellular processes, including normal bone organogenesis and homeostasis, by enhancing or inhibiting bone marrow cell growth, differentiation, functional activity and crosstalk of the multiple cell types within the bone. Hence, elucidating miRNA targets in bone marrow stromal cells has revealed novel regulations during bone development and maintenance. Moreover, recent studies have detailed the capacity for bone stromal miRNAs to influence bone metastasis from a number of primary carcinomas by interfering with bone homeostasis or by directly influencing metastatic tumor cells. Owing to the current lack of good diagnostic biomarkers of bone metastases, such changes in bone stromal miRNA expression in the presence of metastatic lesions may become useful biomarkers, and may even serve as therapeutic targets. In particular, cell-free and exosomal miRNAs shed from bone stromal cells into circulation may be developed into novel biomarkers that can be routinely measured in easily accessible samples. Taken together, these findings reveal the significant role of bone marrow stroma-derived miRNAs in the regulation of bone homeostasis and bone metastasis. Biogenesis and Function of miRNAsMicroRNAs (miRNAs) are a large family of noncoding B22-nucleotide-long RNA molecules that negatively regulate gene expression. 1 It is estimated that miRNAs regulate about 50% of all protein-coding genes. 2 They repress gene expression through complementary binding to sites in the 3 0 -untranslated region (UTR) of target mRNAs. 3,4 miRNA-mediated inhibition occurs either by mRNA degradation or translational silencing. Cleavage of target mRNAs occurs when the miRNA and the target mRNA exhibit perfect complementarity. 3 Conversely, miRNA-mRNA pairings with imperfect complementarity result in translational inhibition in the absence of target cleavage. 3,5 Thus, even in the absence of perfect binding, the association between an miRNA and a target 3 0 -UTR still results in the suppression of a target protein. Owing to the relatively short length of the seed sequence that binds to the 3 0 -UTR (5-7 nucleotides), each miRNA can potentially recognize hundreds of mRNAs and is thus a powerful molecular manager that can control several gene regulatory networks simultaneously.miRNA genes are typically transcribed into stem-loop structures from intra-or intergenic regions by RNA polymerase II and undergo sequential cleavage steps to produce mature miRNAs. 2 In the nucleus, newly transcribed pri-miRNAs (primary miRNAs) are cleaved by a complex formed by the RNase III enzyme Drosha and the double-stranded RNA-binding protein Pasha (or DGCR8) to produce precursor miRNAs. These precursor miRNAs are about 70-100 nucleotides long. 6 They are exported from the nucleus by Exportin 5 and the Ran-GTP cofactor, 7 where they undergo a second cleavage by the endoribonuclease Dicer to produce a double-stranded, B18-2...

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Down-Regulation of miR-183 Promotes Migration and Invasion of Osteosarcoma by Targeting Ezrin

Cited by 136 publications

References 51 publications

microRNA: New Players in Metastatic Process

microRNA: New Players in Metastatic Process

MicroRNAs as regulators of bone homeostasis and bone metastasis

Bone marrow stroma-derived miRNAs as regulators, biomarkers and therapeutic targets of bone metastasis

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