MicroRNA-143 Regulates Human Osteosarcoma Metastasis by Regulating Matrix Metalloprotease-13 Expression

Osaki, Mitsuhiko; Takeshita, Fumitaka; Sugimoto, Yui; Kosaka, Nobuyoshi; Yamamoto, Yusuke; Yoshioka, Yusuke; Kobayashi, Eisuke; Yamada, Tesshi; Kawai, Akira; Inoue, Toshiaki; Ito, Hisao; Oshimura, Mitsuo; Ochiya, Takahiro

doi:10.1038/mt.2011.53

Cited by 235 publications

(198 citation statements)

References 47 publications

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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%

“…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. 40 MiR-21 was similarly shown to function as a driver of osteosarcoma migration and invasion, and suppression of miR-21 reduced motility in osteosarcoma cell lines by direct targeting of RECK.…”

Section: Mirna Expression Influences Growth and Progression Of Osteosmentioning

confidence: 99%

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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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Section: Mirna Expression Influences Growth and Progression Of Osteosmentioning

confidence: 99%

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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“…Numerous reports have identified significantly reduced miR-143 expression in various tumors such as non-small cell lung, colorectal, gastric, pancreatic and prostate cancers, osteosarcomas, cervical cancer and leukemia (9)(10)(11)(12)(13)(14)(15)(16). However, to our knowledge, the current study is the first to investigate the function of miR-143 in regulating human HCC.…”

Section: Introductionmentioning

confidence: 63%

“…miR-143 expression in lung cancer tissues and identified that CD44 might be a direct target of miR-143 (24). MiR-143 is also involved in the suppression of bladder cancer and osteosarcoma by targeting cyclooxygenase-2 and matrix metalloprotease-13 (15,25), and the progression of colorectal cancer is reported to be significantly correlated with lower miR-143 expression (11). Xu et al overexpressed miR-143 in prostate cancer cells and observed that miR-143 transfection could effectively increase the sensitivity to docetaxel treatment, probably through RAS/MAPK signaling (26).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-143 inhibits tumorigenesis in hepatocellular carcinoma by downregulating GATA6

Xue

Yin

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. MicroRNAs serve a critical role in human hepatocellular carcinoma (HCC) progression. However, the exact role of microRNA-143 (miR-143) in HCC remains unclear. The current study investigates the molecular mechanism of miR-143 in HCC. In cultured HepG2 and Bel7402 cell lines, miR-143 levels were raised by lentivirus transduction. This significantly inhibited HCC progression in terms of cell invasion and proliferation in both HepG2 and Bel7402 cell lines (P<0.05). MiR-143 also significantly decreased tumor implantation in vivo (P<0.05). Regulation of miR-143 on its direct target, GATA-binding factor 6 (GATA6), was investigated by multiple strategies, including dual-luciferase assay, quantitative polymerase chain reaction and western blot analysis. The results indicated that miR-143 was downregulated in both HCC cell lines and human tumors. GATA6 was identified as the downstream target of miR-143 in HCC, and overexpressing GATA6 was able to counter the tumor-suppressive effect of miR-143 on HCC in HepG2 and Bel7402 cells by significantly increasing proliferation and invasion rates (P<0.05). Therefore, a novel epigenetic pathway was identified in which miR-143 may suppress the malignancy of HCC by targeting GATA6.

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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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MicroRNA-143 Regulates Human Osteosarcoma Metastasis by Regulating Matrix Metalloprotease-13 Expression

Cited by 235 publications

References 47 publications

MicroRNAs as regulators of bone homeostasis and bone metastasis

MicroRNAs as regulators of bone homeostasis and bone metastasis

MicroRNA-143 inhibits tumorigenesis in hepatocellular carcinoma by downregulating GATA6

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

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