Loss of RUNX3 expression may contribute to poor prognosis in patients with chondrosarcoma

Jin, Zhe; Han, Yaxin; Han, Xianlin

doi:10.1007/s10735-013-9511-x

Cited by 25 publications

(23 citation statements)

References 21 publications

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“…A high rate of apoptosis was also confirmed in cDNA-transfected cells versus untransfected cells. Collectively, hypermethylation of RUNX3 correlated with increasing proliferation and reducing apoptosis in CS cells in vitro [25]. Hypermethylation of tumor-related genes in human CS is shown in Figure 1.…”

Section: Dna Hypermethylation and Abnormalities In Csmentioning

confidence: 87%

“…DNA hypermethylation contributes to the development of CS via various cell pathways, including cell cycle, apoptosis, cell adherence and cell-to-cell interaction [25][26][27][28]. For example, P16 INK4a , a well-known tumor suppressor gene, was found to be hypermethylated in the promoter region in CS [26].…”

Section: Dna Hypermethylation and Abnormalities In Csmentioning

confidence: 99%

“…Additionally, hypermethylation influences the gene expression of upstream regulators. In CS patient specimens, the hypermethylation of RUNX3, an encoding transcription factor regulating cell cycle arrest and apoptosis, acting as a tumor suppressor was examined by MSP [25]. Western blot and real-time PCR for mRNA exhibited a reduction of RUNX3 protein levels as well as a low transcription level in CS tissues relative to normal tissues [25].…”

Section: Dna Hypermethylation and Abnormalities In Csmentioning

confidence: 99%

“…In CS patient specimens, the hypermethylation of RUNX3, an encoding transcription factor regulating cell cycle arrest and apoptosis, acting as a tumor suppressor was examined by MSP [25]. Western blot and real-time PCR for mRNA exhibited a reduction of RUNX3 protein levels as well as a low transcription level in CS tissues relative to normal tissues [25]. Furthermore, a correlation was observed between RUNX3 promoter hypermethylation and downregulated expression, implicating hypermethylation of RUNX3 as a mechanism of inactivating gene expression.…”

Section: Dna Hypermethylation and Abnormalities In Csmentioning

confidence: 99%

“…Human CS tissues Induce cell cycle arrest and apoptosis Hypermethylation [25] † Induced hypomethylation denotes certain gene is detected as hypomethylated after using DNA methyltransferase inhibitor but unknown methylation status in CS. CS: Chondrosarcoma; HS: Heparan sulfate.…”

Section: Runx3mentioning

confidence: 99%

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Aberrant DNA Methylations in Chondrosarcoma

Liu

Shen

et al. 2016

Epigenomics

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Chondrosarcoma (CS) is the second most common primary malignant bone tumor. Unlike other bone tumors, CS is highly resistant to conventional chemotherapy and radiotherapy, thus resulting in poor patient outcomes. There is an urgent need to establish alternative therapies for CS. However, the etiology and pathogenesis of CS still remain elusive. Recently, DNA methylation-associated epigenetic changes have been found to play a pivotal role in the initiation and development of human cancers, including CS, by regulating target gene expression in different cellular pathways. Elucidating the mechanisms of DNA methylation alteration may provide biomarkers for diagnosis and prognosis, as well as novel treatment options for CS. We have conducted a critical review to summarize the evidence regarding aberrant DNA methylation patterns as diagnostic biomarkers, predictors of progression and potential treatment strategies in CS.

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Section: Dna Hypermethylation and Abnormalities In Csmentioning

confidence: 87%

Section: Dna Hypermethylation and Abnormalities In Csmentioning

confidence: 99%

Section: Dna Hypermethylation and Abnormalities In Csmentioning

confidence: 99%

Section: Dna Hypermethylation and Abnormalities In Csmentioning

confidence: 99%

Section: Runx3mentioning

confidence: 99%

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Aberrant DNA Methylations in Chondrosarcoma

Liu

Shen

et al. 2016

Epigenomics

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Loss of RUNX3 expression promotes cancer‐associated bone destruction by regulating CCL5, CCL19 and CXCL11 in non‐small cell lung cancer

Park

Lee

Kim

et al. 2015

The Journal of Pathology

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Non‐small cell lung cancer (NSCLC) frequently metastasizes to bone, which is associated with significant morbidity and a dismal prognosis. RUNX3 functions as a tumour suppressor in lung cancer and loss of expression occurs more frequently in invasive lung adenocarcinoma than in pre‐invasive lesions. Here, we show that RUNX3 and RUNX3‐regulated chemokines are linked to NSCLC‐mediated bone resorption. Notably, the receptor activator of nuclear factor‐κB ligand (RANKL)/osteoprotegerin (OPG) ratio, an index of osteoclastogenic stimulation, was significantly increased in human osteoblastic cells treated with conditioned media derived from RUNX3‐knockdown NSCLC cells. We aimed to identify RUNX3‐regulated factors that modify the osteoblastic RANKL/OPG ratio and found that RUNX3 knockdown led to CCL5 up‐regulation and down‐regulation of CCL19 and CXCL11 in NSCLC cells. Tumour size was noticeably increased and more severe osteolytic lesions were induced in the calvaria and tibiae of mice that received RUNX3‐knockdown cells. In response to RUNX3 knockdown, serum and tissue levels of CCL5 increased, whereas CCL19 and CXCL11 decreased. Furthermore, CCL5 increased the proliferation, migration, and invasion of lung cancer cells in a dose‐dependent manner; however, CCL19 and CXCL11 did not show any significant effects. The RANKL/OPG ratio in osteoblastic cells was increased by CCL5 but reduced by CCL19 and CXCL11. CCL5 promoted osteoclast differentiation, but CCL19 and CXCL11 reduced osteoclastogenesis in RANKL‐treated bone marrow macrophages. These findings suggest that RUNX3 and related chemokines are useful markers for the prediction and/or treatment of NSCLC‐induced bone destruction. © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

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Runx3 and Cell Fate Decisions in Pancreas Cancer

Whittle

Hingorani

2017

Advances in Experimental Medicine and Biology

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The RUNX family transcription factors are critical regulators of development and frequently dysregulated in cancer. RUNX3, the least well characterized of the three family members, has been variously described as a tumor promoter or suppressor, sometimes with conflicting results and opinions in the same cancer and likely reflecting a complex role in oncogenesis. We recently identified RUNX3 expression as a crucial determinant of the predilection for pancreatic ductal adenocarcinoma (PDA) cells to proliferate locally or promulgate throughout the body. High RUNX3 expression induces the production and secretion of soluble factors that support metastatic niche construction and stimulates PDA cells to migrate and invade, while simultaneously suppressing proliferation through increased expression of cell cycle regulators such as CDKN1A/p21 . RUNX3 expression and function are coordinated by numerous transcriptional and post-translational inputs, and interactions with diverse cofactors influence whether the resulting RUNX3 complexes enact tumor suppressive or tumor promoting programs. Understanding these exquisitely context-dependent tumor cell behaviors has the potential to inform clinical decision-making including the most appropriate timing and sequencing of local vs. systemic therapies.

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Loss of RUNX3 expression may contribute to poor prognosis in patients with chondrosarcoma

Cited by 25 publications

References 21 publications

Aberrant DNA Methylations in Chondrosarcoma

Aberrant DNA Methylations in Chondrosarcoma

Loss of RUNX3 expression promotes cancer‐associated bone destruction by regulating CCL5, CCL19 and CXCL11 in non‐small cell lung cancer

Runx3 and Cell Fate Decisions in Pancreas Cancer

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