• Molecules and Cells
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• 제43권2호
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• pp.198-202
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• 2020

Comprehensive inhibition of RUNX1, RUNX2, and RUNX3 led to marked cell suppression compared with inhibition of RUNX1 alone, clarifying that the RUNX family members are important for proliferation and maintenance of diverse cancers, and "cluster regulation of RUNX (CROX)" is a very effective strategy to suppress cancer cells. Recent studies reported by us and other groups suggested that wild-type RUNX1 is needed for survival and proliferation of certain types of leukemia, lung cancer, gastric cancer, etc. and for their one of metastatic target sites such as born marrow endothelial niche, suggesting that RUNX1 often functions oncogenic manners in cancer cells. In this review, we describe the significance and paradoxical requirement of RUNX1 tumor suppressor in leukemia and even solid cancers based on recent our findings such as "genetic compensation of RUNX family transcription factors (the compensation mechanism for the total level of RUNX family protein expression)", "RUNX1 inhibition-induced inhibitory effects on leukemia cells and on solid cancers through p53 activation", and "autonomous feedback loop of RUNX1-p53-CBFB in acute myeloid leukemia cells". Taken together, these findings identify a crucial role for the RUNX cluster in the maintenance and progression of cancers and suggest that modulation of the RUNX cluster using the pyrrole-imidazole polyamide gene-switch technology is a potential novel therapeutic approach to control cancers.

• Molecules and Cells
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• 제43권2호
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• pp.107-113
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• 2020

The Runt-related transcription factors (RUNX) transcription factors have been known for their critical roles in numerous developmental processes and diseases such as autoimmune disorders and cancer. Especially, RUNX proteins are best known for their roles in hematopoiesis, particularly during the development of T cells. As scientists discover more types of new immune cells, the functional diversity of RUNX proteins also has been increased over time. Furthermore, recent research has revealed complicated transcriptional networks involving RUNX proteins by the current technical advances. Databases established by next generation sequencing data analysis has identified ever increasing numbers of potential targets for RUNX proteins and other transcription factors. Here, we summarize diverse functions of RUNX proteins mainly on lymphoid lineage cells by incorporating recent discoveries.

• Molecules and Cells
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• 제43권2호
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• pp.99-106
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• 2020

Cells are constantly exposed to endogenous and exogenous stresses that can result in DNA damage. In response, they have evolved complex pathways to maintain genomic integrity. RUNX family transcription factors (RUNX1, RUNX2, and RUNX3 in mammals) are master regulators of development and differentiation, and are frequently dysregulated in cancer. A growing body of research also implicates RUNX proteins as regulators of the DNA damage response, often acting in conjunction with the p53 and Fanconi anemia pathways. In this review, we discuss the functional role and mechanisms involved in RUNX factor mediated response to DNA damage and other cellular stresses. We highlight the impact of these new findings on our understanding of cancer predisposition associated with RUNX factor dysregulation and their implications for designing novel approaches to prevent cancer formation in affected individuals.

• Molecules and Cells
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• 제43권2호
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• pp.176-181
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• 2020

The RUNX transcription factors serve as master regulators of development and are frequently dysregulated in human cancers. Among the three family members, RUNX3 is the least studied, and has long been considered to be a tumor-suppressor gene in human cancers. This idea is mainly based on the observation that RUNX3 is inactivated by genetic/epigenetic alterations or protein mislocalization during the initiation of tumorigenesis. Recently, this paradigm has been challenged, as several lines of evidence have shown that RUNX3 is upregulated over the course of tumor development. Resolving this paradox and understanding how a single gene can exhibit both oncogenic and tumor-suppressive properties is essential for successful drug targeting of RUNX. We propose a simple explanation for the duality of RUNX3: p53 status. In this model, p53 deficiency causes RUNX3 to become an oncogene, resulting in aberrant upregulation of MYC.

• Molecules and Cells
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• 제43권2호
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• pp.188-197
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• 2020

Cells are designed to be sensitive to a myriad of external cues so they can fulfil their individual destiny as part of the greater whole. A number of well-characterised signalling pathways dictate the cell's response to the external environment and incoming messages. In healthy, well-ordered homeostatic systems these signals are tightly controlled and kept in balance. However, given their powerful control over cell fate, these pathways, and the transcriptional machinery they orchestrate, are frequently hijacked during the development of neoplastic disease. A prime example is the Wnt signalling pathway that can be modulated by a variety of ligands and inhibitors, ultimately exerting its effects through the β-catenin transcription factor and its downstream target genes. Here we focus on the interplay between the three-member family of RUNX transcription factors with the Wnt pathway and how together they can influence cell behaviour and contribute to cancer development. In a recurring theme with other signalling systems, the RUNX genes and the Wnt pathway appear to operate within a series of feedback loops. RUNX genes are capable of directly and indirectly regulating different elements of the Wnt pathway to either strengthen or inhibit the signal. Equally, β-catenin and its transcriptional co-factors can control RUNX gene expression and together they can collaborate to regulate a large number of third party co-target genes.

• 대한소아치과학회지
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• 제46권4호
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• pp.409-415
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• 2019

쇄골 두개 이형성증(Cleidocranial dysplasia)은 상염색체 우성의 유전질환으로, 두개골 간 봉합 지연, 쇄골의 이형성, 과잉치, 영구치 맹출 지연 등을 특징으로 한다. 경조직 형성 조절 인자인 Runt-related transcription factor 2 (RUNX2)의 돌연변이가 쇄골 두개 이형성증을 유발하는 주요 요인으로 보고되고 있다. 이 연구는 치아 맹출 지연이 관찰되는 쇄골 두개 이형성증 가계에서 분자유전학적 원인을 규명하고자 하였다. 23세 여성 환자와 그 어머니를 대상으로 임상 검사 및 방사선 검사를 진행하였고 RUNX2 유전자의 염기 서열을 분석하였다. 대상자 모두에서 3번 exon 내의 단일 염기 결손 돌연변이(NM_001024630.4: c.357delC)를 확인하였다. 이로 인해 frameshift가 발생하여 조기 종결 코돈이 형성될 것으로 예측되며[p.(Asn120Thrfs^*24)], 이로 인한 RUNX2 단백질의 기능 손상이 해당 가계에서 나타난 영구치 맹출 지연의 병인이 되었을 것으로 여겨진다.

• Journal of Periodontal and Implant Science
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• 제40권1호
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• pp.39-44
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• 2010

Purpose: Bone tissues for clinical application can be improved by studies on osteoblast differentiation. Runx2 is known to be an important transcription factor for osteoblast differentiation. However, bone morphogenetic protein (BMP)-2 treatment to stimulate Runx2 is not sufficient to acquire enough bone formation in osteoblasts. Therefore, it is necessary to find other regulatory factors which can improve the transcriptional activity of Runx2. The erythroblast transformation-specific (ETS) transcription factor family is reported to be involved in various aspects of cellular proliferation and differentiation. Methods: We have noticed that the promoters of osteoblast differentiation markers such as alkaline phosphatase (Alp), osteopontin (Opn), and osteocalcin (Oc) contain Ets binding sequences which are also close to Runx2 binding elements. Luciferase assays were performed to measure the promoter activities of these osteoblast differentiation markers after the transfection of Runx2, myeloid Elf-1-like factor (MEF), and Runxs+MEF. Reverse-transcription polymerase chain reaction was also done to check the mRNA levels of Opn after Runx2 and MEF transfection into rat osteoblast (ROS) cells. Results: We have found that MEF, an Ets transcription factor, increased the transcriptional activities of Alp, Opn, and Oc. The addition of Runx2 resulted in the 2- to 6-fold increase of the activities. This means that these two transcription factors have a synergistic effect on the osteoblast differentiation markers. Furthermore, early introduction of these two Runx2 and MEF factors significantly elevated the expression of the Opn mRNA levels in ROS cells. We also showed that Runx2 and MEF proteins physically interact with each other. Conclusions: Runx2 interacts with MEF proteins and binds to the promoters of the osteoblast markers such as Opn nearby MEF to increase its transcriptional activity. Our results also imply that osteoblast differentiation and bone formation can be increased by activating MEF to elicit the synergistic effect of Runx2 and MEF.

• Molecules and Cells
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• 제42권12호
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• pp.836-839
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• 2019

A tumor is an abnormal mass of tissue that arises when cells divide more than they should or do not die when they should. The cellular decision regarding whether to undergo division or death is made at the restriction (R)-point. Consistent with this, an increasingly large body of evidence indicates that deregulation of the R-point decision-making machinery accompanies the formation of most tumors. Although the R-point decision is literally a matter of life and death for the cell, and thus critical for the health of the organism, it remains unclear how a cell chooses its own fate. Recent work demonstrated that the R-point constitutes a novel oncogene surveillance mechanism operated by R-point-associated complexes of which RUNX3 and BRD2 are the core factors (Rpa-RX3 complexes). Here, we show that not only RUNX3 and BRD2, but also other members of the RUNX and BRD families (RUNX1, RUNX2, BRD3, and BRD4), are involved in R-point regulation.

• Molecules and Cells
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• 제43권2호
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• pp.97-98
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• 2020

• 대한소아치과학회지
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• 제31권4호
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• pp.651-658
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• 2004

Runx2는 runt gene family에 속하는 전사조절 인자로써 뼈의 형성과 골아세포의 분화에 중요한 역할을 담당하고 있다. Runx2-haploinsufficency는 쇄골의 저형성 및 두개 봉합의 지연을 특징으로 하는 쇄골두개 이형성증을 일으키며, 치아에 있어서는 법랑질의 저형성, 영구치 맹출지연 등을 보인다. 이에, 치아의 발육 및 맹출에 미치는 Runx2의 영향을 알아보기 위해 in situ hybridization 방법으로 태생 1, 4, 7, 14, 21일 된 쥐의 하악 및 제1대구치를 사용하여 실험을 실시하였다. Runx2-full length는 태생 1일과 4일에 치낭 및 그 주위조직에 보이지만 Runx2-typeII는 보이지 않았다 Runx2-full length는 태생 7일에 치관 교합면 부위의 법랑모세포에 발현하였고, 1주일 후인 태생 14일에는 백악법랑경계 상방의 치관인접면 법랑모세포에서 발현되었다. 이에 반해 Runx2-typeII는 법랑모세포에서 발현하지 않았다. 또한 태생 21일에서는 두 가지 이성질체가 모두 하악골에서 발현을 보였다 이런 결과를 종합해볼 때, Runx2-full length는 치아의 맹출과 연관이 있으며, 법랑모세포의 분화 및 이로 인한 법랑질형성에 영향을 주지만 Runx2-typeII는 하악골의 형성에만 영향을 미치는 것으로 사료된다.