miR-196a Regulates Proliferation and Osteogenic Differentiation in Mesenchymal Stem Cells Derived From Human Adipose Tissue

Kim, Yeon Jeong; Bae, S; Yu, Sung Sook; Bae, Yong Chan; Jung, Jin Sup

doi:10.1359/jbmr.081230

Cited by 226 publications

(155 citation statements)

References 34 publications

Supporting

Mentioning

142

Contrasting

Unclassified

Order By: Relevance

“…40 In addition, overexpression of miR-196a inhibited the proliferation of human adipose tissue-derived mesenchymal stem cells while enhancing osteogenic differentiation. 41 Our results show that NPC cells become radioresistant by reducing the expression of miR--196a, and expression of miR-196a restores the sensitivity of radioresistant NPC to radiation therapy. Importantly, the expression level of miR-196a in clinical NPC samples is correlated with the sensitivity of NPC to radiotherapy.…”

Section: Discussionmentioning

confidence: 53%

IKKα-mediated biogenesis of miR-196a through interaction with Drosha regulates the sensitivity of cancer cells to radiotherapy

et al. 2016

View full text Add to dashboard Cite

Radioresistance is a major obstacle in successful clinical cancer radiotherapy, and the underlying mechanisms are not clear. Here we show that IKKα-mediated miR-196a biogenesis via interaction with Drosha regulates the sensitivity of nasopharyngeal carcinoma (NPC) cells to radiotherapy. Phosphorylation of IKKα at T23 site (p-IKKαT23) promotes the binding of IKKα to Drosha that accelerates the processing of miR-196a primary transcripts, leading to increased expressions of both precursor and mature miR-196a. Dephosphorylation of p-IKKαT23 downregulates miR-196a expression and promotes the resistance of NPC cells to radiation treatment. The miR-196a mimic suppresses while its inhibitor promotes the resistance of NPC to radiation treatment. Importantly, the expression of p-IKKαT23 is positively related to the expression of miR-196a in human NPC tissues, and expression of p-IKKαT23 and miR-196a is inversely correlated with NPC clinical radioresistance. Thus, our studies establish a novel mechanistic link between the inactivation of IKKαT23-Drosha-miR-196a pathway and NPC radioresistance, and de-inactivation of IKKαT23-Drosha-miR-196a pathway would be an efficient way to restore the sensitivity of radioresistant NPC to radiotherapy.

show abstract

Section: Discussionmentioning

confidence: 53%

IKKα-mediated biogenesis of miR-196a through interaction with Drosha regulates the sensitivity of cancer cells to radiotherapy

et al. 2016

View full text Add to dashboard Cite

show abstract

“…For example, the misexpression of miR-196a in the anterior of Xenopus laevis embryos caused eye anomalies (Qiu et al, 2009). Moreover, Kim et al (2009) showed that miR-196a was an important regulator for the proliferation and osteogenic differentiation of human adipose tissuederived mesenchymal stem cells.…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of serum miR-196a in cervical intraepithelial neoplasia and cervical cancer

Liu¹,

Xin²,

F³

2015

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. Previous studies have reported that miR-196a is upregulated in cervical cancer tissues and cell lines. However, whether serum miR196a is increased in patients with cervical cancer or cervical intraepithelial neoplasia (CIN), and its potential clinical value remained unknown. In total, 105 cervical cancer patients, 86 CIN patients, and 50 healthy volunteers were recruited. Quantitative reverse transcription-polymerase chain reaction was performed to compare the serum levels miR-196a in all participants. The associations between serum miR-196a and CIN grade/ clinicopathological parameters of cervical cancer were also examined. A survival analysis was performed using the Kaplan-Meier method. Univariate and multivariate analyses were conducted to explore the independent risk factors for cervical cancer. Our results revealed that serum miR196a levels were higher in patients with cervical cancer (P < 0.01) and CIN (P < 0.05) compared to those in healthy controls. Serum miR-196a was associated with CIN grade and various cervical cancer parameters including tumor size (P = 0.031), lymph node metastasis (P = 0.018),

show abstract

“…However, Runx2 has been shown to negatively regulate expression of the miR cluster 23a∼27a∼24-2, thereby increasing expression of bone markers and enhancing osteoblast differentiation (14). In human adipose tissue-derived MSCs (hADSCs), miR-26a has been reported to repress the translation of the osteogenic marker, SMAD1 (15), whereas overexpression of miR-196a regulates HOXC8, enhances osteogenic differentiation, and decreases hADSC proliferation (16). miR-125b has been shown to inhibit osteoblast differentiation in the mouse MSC line ST2 (17), whereas miR-133 and -135 directly target Runx2 and Smad5, respectively, and inhibit differentiation of osteoprogenitors of C2C12 mesenchymal cells (18).…”

mentioning

confidence: 99%

MicroRNA-138 regulates osteogenic differentiation of human stromal (mesenchymal) stem cells in vivo

Eskildsen

Taipaleenmäki

Stenvang

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

444

354

View full text Add to dashboard Cite

Elucidating the molecular mechanisms that regulate human stromal (mesenchymal) stem cell (hMSC) differentiation into osteogenic lineage is important for the development of anabolic therapies for treatment of osteoporosis. MicroRNAs (miRNAs) are short, noncoding RNAs that act as key regulators of diverse biological processes by mediating translational repression or mRNA degradation of their target genes. Here, we show that miRNA-138 (miR-138) modulates osteogenic differentiation of hMSCs. miRNA array profiling and further validation by quantitative RT-PCR (qRT-PCR) revealed that miR-138 was down-regulated during osteoblast differentiation of hMSCs. Overexpression of miR-138 inhibited osteoblast differentiation of hMSCs in vitro, whereas inhibition of miR-138 function by antimiR-138 promoted expression of osteoblast-specific genes, alkaline phosphatase (ALP) activity, and matrix mineralization. Furthermore, overexpression of miR-138 reduced ectopic bone formation in vivo by 85%, and conversely, in vivo bone formation was enhanced by 60% when miR-138 was antagonized. Target prediction analysis and experimental validation by luciferase 3′ UTR reporter assay confirmed focal adhesion kinase, a kinase playing a central role in promoting osteoblast differentiation, as a bona fide target of miR-138. We show that miR-138 attenuates bone formation in vivo, at least in part by inhibiting the focal adhesion kinase signaling pathway. Our findings suggest that pharmacological inhibition of miR-138 by antimiR-138 could represent a therapeutic strategy for enhancing bone formation in vivo.regulatory RNA | bone biology | osteoblastic differentiation

show abstract

miR-196a Regulates Proliferation and Osteogenic Differentiation in Mesenchymal Stem Cells Derived From Human Adipose Tissue

Cited by 226 publications

References 34 publications

IKKα-mediated biogenesis of miR-196a through interaction with Drosha regulates the sensitivity of cancer cells to radiotherapy

IKKα-mediated biogenesis of miR-196a through interaction with Drosha regulates the sensitivity of cancer cells to radiotherapy

Clinical significance of serum miR-196a in cervical intraepithelial neoplasia and cervical cancer

MicroRNA-138 regulates osteogenic differentiation of human stromal (mesenchymal) stem cells in vivo

Contact Info

Product

Resources

About