RUNX2: A Master Bone Growth Regulator That May Be Involved in the DNA Damage Response

Wysokiński, Daniel; Pawłowska, Elżbieta; Błasiak, Janusz

doi:10.1089/dna.2014.2688

Cited by 47 publications

(33 citation statements)

References 109 publications

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“…Runt-related transcription factors 2 (Runx2) is a key specific regulator of osteoblast differentiation, and its mutation associates with human cleidocranial dysplasia [7][8][9]. Runx2 stimulates the maturation of osteoblasts during bone differentiation [10].…”

Section: Introductionmentioning

confidence: 99%

MiR-30a regulates the proliferation, migration, and invasion of human osteosarcoma by targeting Runx2

et al. 2015

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Osteosarcoma (OS) is the most common primary malignant bone tumor in young patients. However, treatment paradigms and survival rates have not improved in decades. MicroRNAs have been shown to be critical regulators of physiological homeostasis and pathological process, including bone disease. Nearly half of the microRNA (miRNA) genes are located at genomic regions and fragile sites known to be frequently deleted or amplified in various kinds of cancers. In this study, we investigated the role miR-30a in OS. A negative correlation between miR-30a expression and malignant grade was observed in OS cell lines. The overexpression of miR-30a reduced proliferation, migration, and invasion in 143B cells and the inhibitor of miR-30a increased proliferation, migration, and invasion in Saos2 cells. Further studies revealed that runt-related transcription factors 2 (Runx2) was a regulative target gene of miR-30a. Rescue assay significantly reversed the effects of overexpressing or inhibiting miR-30a. miR-30a also suppressed tumor formation and pulmonary metastasis in vivo. All the results suggest a critical role of miR-30a in suppressing proliferation, migration, and invasion of OS by targeting Runx2.

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Section: Introductionmentioning

confidence: 99%

MiR-30a regulates the proliferation, migration, and invasion of human osteosarcoma by targeting Runx2

et al. 2015

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“…Runt-related transcription factor 2 (Runx2), is identified as a "master gene" required for osteoblastic differentiation process from mesenchymal precursors (Tu et al, 2007b;Vimalraj et al, 2015;Wysokinski et al, 2015). Our previous studies, showed that, haploinsufficiency of Runx2 results in decreased bone formation and changes in BSP expression patterns (Li et al, 2005a;Tu et al, 2007bTu et al, , 2008Tu et al, , 2009).…”

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confidence: 99%

Runx2/DICER/miRNA Pathway in Regulating Osteogenesis

Zheng

Shao

et al. 2016

J. Cell. Physiol

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DICER is the central enzyme that cleaves precursor microRNAs (miRNAs) into 21-25 nucleotide duplex in cell lineage differentiation, identity and survival. In the current study, we characterized the specific bone metabolism genes and corresponding miRNAs and found that DICER and Runt-related transcription factor 2 (Runx2) expressions increased simultaneously during osteogenic differentiation. Luciferase assay showed that Runx2 significantly increased the expression levels of DICER luciferase promoter reporter. Our analysis also revealed weaker DICER expression in embryos of Runx2 knock out mice (Runx2 −/−) compared with that of Runx2 +/− and Runx2 +/+ mice. We further established the calvarial bone critical-size defect (CSD) mouse model. The bone marrow stromal cells (BMSCs) transfected with siRNA targeting DICER were combined with silk scaffolds and transplanted into calvarial bone CSDs. Five weeks post-surgery, micro-CT analysis revealed impaired bone formation and repairing in calvarial defects with the siRNA targeting DICER group. In conclusion, our results suggest that DICER is specifically regulated by osteogenic master gene Runx2 that binds to the DICER promoter. Consequently, DICER cleaves precursors of miR-335-5p and miR-17-92 cluster to form mature miRNAs, which target and decrease the Dickkopf-related protein 1 (DKK1) and proapoptotic factor BIM levels, respectively, leading to an enhanced Wnt/β-catenin signaling pathway. These intriguing results reveal a central mechanism underlying lineage-specific regulation by a Runx2/DICER/miRNAs cascade during osteogenic differentiation and bone development. Our study also suggests a potential application of modulating DICER expression for bone tissue repair and regeneration.

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“…Cells in the G2 and M phases of the cell cycle are sensitive to interventions such as 5-FU and radiation [30, 32]. To determine the cell cycle progression of colorectal cancer cells after treatment with 5-FU, exponentially growing cancer cells were exposed to 5-FU and then were analyzed by flow cytometry.…”

Section: Resultsmentioning

confidence: 99%

XRCC2-Deficient Cells are Highly Sensitive to 5-Fluorouracil in Colorectal Cancer

Zhang¹,

An²,

Liu³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Inhibition of the repair of 5-fluorouracil (5-FU)-induced DNA lesions may improve the responses of tumors to anticancer agents. XRCC2 is a key factor in DNA repair. However, the role of XRCC2 in the chemoresistance of colorectal cancer (CRC) treated with 5-FU remains unclear. The aim of this study is to investigate whether XRCC2 expression affects the chemosensitivity of colorectal cancer. Methods: XRCC2 expression in CRC tissues was assessed, and the outcomes were analyzed to determine the clinical importance of XRCC2 expression. Following treatment with 5-FU, the effect of XRCC2 on proliferation was evaluated via a CCK-8 assay, the effects on cell cycle distribution and apoptosis were analyzed using flow cytometry, and γH2AX foci formation assays were performed to examine the influence of 5-FU on DNA Double-strand breaks(DSBs) repair in CRC cells. Results: XRCC2 expression in CRC tissues was significantly higher than that in normal tissues, and this increased XRCC2 expression was associated with advanced T staging, M staging, TNM staging, Duke’s staging, and greater liver and lymph node metastases. XRCC2 expression might be an independent prognostic indicator for CRC patients. Patients with negative XRCC2 expression exhibit greater sensitivity to treatment with 5-FU-based chemotherapy than those with positive XRCC2 expression. Moreover, our observations revealed that the knockdown of XRCC2 in CRC cells increased the sensitivities to 5-FU in terms of cell proliferation, apoptosis and cell cycle arrest. DNA DSBs repair was slower in the XRCC2-deficient cells than in the XRCC2-wild type cells. Conclusion: Our study demonstrated that XRCC2 might play an important role in CRC and function as a novel prognostic indicator and that the down-regulation of XRCC2 may be useful for sensitizing CRC cells during 5-FU chemotherapy.

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RUNX2: A Master Bone Growth Regulator That May Be Involved in the DNA Damage Response

Cited by 47 publications

References 109 publications

MiR-30a regulates the proliferation, migration, and invasion of human osteosarcoma by targeting Runx2

MiR-30a regulates the proliferation, migration, and invasion of human osteosarcoma by targeting Runx2

Runx2/DICER/miRNA Pathway in Regulating Osteogenesis

XRCC2-Deficient Cells are Highly Sensitive to 5-Fluorouracil in Colorectal Cancer

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