miR‐140‐5p suppresses BMP2‐mediated osteogenesis in undifferentiated human mesenchymal stem cells

Hwang, Supyong; Park, Seul-Ki; Lee, Ha Yeon; Kim, Seong Who; Lee, Jung Shin; Choi, Eun Kyung; You, Dalsan; Kim, Choung‐Soo; Suh, Nayoung

doi:10.1016/j.febslet.2014.05.048

Cited by 129 publications

(99 citation statements)

References 39 publications

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“…Meanwhile, PDAC malignancy was found to be positively associated with miR-196a [11], miR-212 [12], and miR-31 [13]. We chose to focus on miR-140 because it is closely related to many different malignancies, such as mastocarcinoma [14], colorectal carcinoma [15], liver cancer [16], and osteosarcoma [17]. Our findings suggest that miR-140 could play tumor-inhibitive role in the above cancers.…”

Section: Introductionmentioning

confidence: 82%

MicroRNA-140 regulates cell growth and invasion in pancreatic duct adenocarcinoma by targeting iASPP

Liang

Gong

Zhang

et al. 2016

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MicroRNAs are ∼22 nucleotide RNAs processed from RNA hairpin structures that play important roles in regulating protein expression level via binding to mRNA, either suppressing its translation or speeding up its degradation. In humans, they regulate most protein-coding genes, including genes important in cancer and other diseases. In this study, the expression of microRNA-140 (miR-140) was demonstrated to be significantly suppressed in pancreatic duct adenocarcinoma specimens and cell lines, compared with their adjacent normal tissues. With the help of bioinformatics analysis, inhibitor of apoptosis-stimulating protein of p53 (iASPP) was identified to be a direct target of miR-140, and luciferase reporter experiment confirmed this discovery. Overexpression of miR-140 decreases the protein expressions of iASPP, ΔNp63, MMP2, and MMP9. Growth and invasion of PANC-1 cells were attenuated by overexpression of miR-140 in vitro. The suppressive effect of miR-140 on PANC-1 cell line could be partly balanced out by manual overexpression of iASPP. Above all, these findings provided insights into the functional mechanism of miR-140, suggested that the miR-140/iASPP axis may interfere with the proliferative and invasive property of pancreatic duct adenocarcinoma cells, and indicated that miR-140 could be a potential therapeutic target for pancreatic duct adenocarcinoma.

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Section: Introductionmentioning

confidence: 82%

MicroRNA-140 regulates cell growth and invasion in pancreatic duct adenocarcinoma by targeting iASPP

Liang

Gong

Zhang

et al. 2016

ABBS

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“…Recently, a growing body of evidence has revealed that miRNAs play essential roles in osteoblast differentiation [22][23][24][25].…”

Section: Discussionmentioning

confidence: 99%

MiR‐144‐3p regulates osteogenic differentiation and proliferation of murine mesenchymal stem cells by specifically targeting Smad4

et al. 2016

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Despite extensive research on osteoblast differentiation and proliferation in mesenchymal stem cells (MSCs), the accurate mechanism remains to be further elucidated. MicroRNAs have been reported to be key regulators of osteoblast differentiation and proliferation. Here, we found that miR‐144‐3p is down‐regulated during osteoblast differentiation of C3H10T1/2 cells. Overexpression of miR‐144‐3p inhibited osteogenic differentiation, whereas inhibition of miR‐144‐3p reversed this process. Furthermore, miR‐144‐3p inhibited the proliferation of C3H10T1/2 cells by arresting cells at the G0/G1 phase. Results from bioinformatics analysis, luciferase assay and western blotting demonstrated that miR‐144‐3p directly targeted Smad4. Additionally, Smad4 knockdown blocks the effects of miR‐144‐3p inhibitor. Therefore, we conclude that miR‐144‐3p negatively regulates osteogenic differentiation and proliferation of C3H10T1/2 cells by targeting Smad4.

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“…miRNA-140-5p and its binding site in the 3 0 UTR of BMP-2 are evolutionarily conserved miRNA-140-5p is able to repress BMP-2 in hMSCs [11], indicating that miRNA-140-5p may directly bind to the 3 0 UTR of BMP-2. Using the TargetScan Fish online algorithm, a potential miRNA-140 target site on the 3 0 UTR of BMP-2 was identified (Fig.…”

Section: Resultsmentioning

confidence: 98%

“…These studies indicated that there may be a regulatory and functional relationship between BMP-2 and miRNA-140-5p. Interestingly, a recent study demonstrated that BMP-2 was repressed by miRNA-140-5p in hMSCs [11], but the regulatory mechanism remained undiscovered. Using methods in bioinformatics, we found that both miRNA-140-5p and the miRNA-140-5p-binding site in the 3 0 UTR of BMP-2 are highly conserved among vertebrates, implying that the negative regulatory mechanism underlying the regulation of BMP-2 by miRNA-140-5p during bone and cartilage development is evolutionarily conserved.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐140‐5p impairs zebrafish embryonic bone development via targeting BMP‐2

et al. 2016

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MicroRNA‐140‐5p (miRNA‐140‐5p) is important for embryonic bone development. In this study, we found that miRNA‐140‐5p and its binding site in the 3′UTR of bone morphogenetic protein 2 (BMP‐2) are highly conserved among vertebrates, and miRNA‐140‐5p negatively regulates both zebrafish and human BMP‐2 genes. Microinjection of miRNA‐140‐5p or BMP‐2b morpholino into zebrafish embryos led to a similar phenotype, including shortened tails, curved trunks, and defects in cranial cartilage. Moreover, miRNA‐140‐5p injection induced zebrafish embryo malformation that could be significantly rescued by microinjection of BMP‐2 mRNA. In conclusion, our results indicated that miRNA‐140‐5p regulates zebrafish embryonic bone development via targeting BMP‐2.

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miR‐140‐5p suppresses BMP2‐mediated osteogenesis in undifferentiated human mesenchymal stem cells

Cited by 129 publications

References 39 publications

MicroRNA-140 regulates cell growth and invasion in pancreatic duct adenocarcinoma by targeting iASPP

MicroRNA-140 regulates cell growth and invasion in pancreatic duct adenocarcinoma by targeting iASPP

MiR‐144‐3p regulates osteogenic differentiation and proliferation of murine mesenchymal stem cells by specifically targeting Smad4

MicroRNA‐140‐5p impairs zebrafish embryonic bone development via targeting BMP‐2

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