Tohoku University · 생화학·유전·분자생물학
Keito Okazaki 교수의 연구실은 비만세포성폐암(NSCLC)에서 NRF2의 만성적 활성화가 암 진행과 치료 내성에 미치는 영향을 중심으로 연구를 진행하고 있습니다. 특히 NRF2와 CEBPB 등 전사 인자의 상호작용을 통해 새로운 에너지 조절 기전과 암세포의 생존 및 발병 메커니즘을 규명하고자 하며, 전사 조절 및 에피제네틱스의 변화가 암의 특성 전환에 어떻게 기여하는지 탐구하고 있습니다. 또한 Regnase-1과 같은 RNA 분해효소의 기능 이상이 폐암 진행에 영향을 미칠 수 있음을 밝혀내며, 전사 후 조절 메커니즘의 역할도 함께 분석하고 있습니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
Transcriptional dysregulation, which can be caused by genetic and epigenetic alterations, is a fundamental feature of many cancers. A key cytoprotective transcriptional activator, NRF2, is often aberrantly activated in non-small cell lung cancers (NSCLCs) and supports both aggressive tumorigenesis and therapeutic resistance. Herein, we find that persistently activated NRF2 in NSCLCs generates enhancers at gene loci that are not normally regulated by transiently activated NRF2 under physiological
The KEAP1-NRF2 system is a sulfur-employing defense mechanism against oxidative and electrophilic stress. NRF2 is a potent transcription activator for genes mediating sulfur-involving redox reactions, and KEAP1 controls the NRF2 activity in response to the stimuli by utilizing reactivity of sulfur atoms. In many human cancer cells, the KEAP1-mediated regulation of NRF2 activity is abrogated, resulting in the persistent activation of NRF2. Persistently activated NRF2 drives malignant progression
NRF2 is a transcription activator that plays a key role in cytoprotection against oxidative stress. Although increased NRF2 activity is principally beneficial for our health, NRF2 activation in cancer cells is detrimental, as it drives their malignant progression. We previously found that CCAAT/enhancer-binding protein B (CEBPB) cooperates with NRF2 in NRF2-activated lung cancer and enhances tumour-initiating activity by promoting NOTCH3 expression. However, the general contribution of CEBPB in
Summary Transcriptional dysregulation, which can be caused by genetic and epigenetic alterations, is a fundamental feature of many cancers. A key cytoprotective transcriptional activator, NRF2, is often aberrantly activated in non-small cell lung cancers (NSCLCs) and supports both aggressive tumorigenesis and therapeutic resistance. Herein, we found that persistently activated NRF2 in NSCLCs generates enhancers at gene loci that are not normally regulated by transiently activated NRF2 under phys
A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-20927-9.
Abstract Regnase-1, encoded by the ZC3H12A gene, is a well-known RNase that suppresses inflammation by degrading the mRNAs of inflammatory cytokines. However, its role in cancer pathogenesis, especially in non-small cell lung cancer (NSCLC), remains poorly understood. Through an analysis of public databases, we found that NSCLC patients with higher ZC3H12A expression levels had a worse prognosis than those with lower levels. To explore the function of Regnase-1 in NSCLC, we knocked out the ZC3H1
Regnase-1, encoded by the ZC3H12A gene, is a well-known RNase that suppresses inflammation by degrading the mRNAs of inflammatory cytokines. However, its role in cancer pathogenesis, especially in non-small cell lung cancer (NSCLC), remains poorly understood. Through an analysis of public databases, we found that NSCLC patients with higher ZC3H12A expression levels had a worse prognosis than those with lower levels. To explore the function of Regnase-1 in NSCLC, we knocked out the ZC3H12A gene i
Sulfur, like oxygen, belongs to Group 16 of the periodic table and is characterized by its flexibility in both donating and accepting electrons, as well as its wide range of oxidation states. These properties enable sulfur to participate in diverse redox reactions. In biological systems, sulfur plays vital roles as a component of catalytic centers of enzymes and as a redox sensor. Moreover, sulfur is the only element known to form stable linear chains through homoelemental bonding, a phenomenon
Light chain-only variant of proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID-LC) and light chain deposition disease (LCDD) are both renal disorders caused by the overproduction of monoclonal immunoglobulin light chains and their deposition in renal tissues. However, the renal pathological features of these two entities are characteristically distinct. We report a rare case of multiple myeloma presenting with renal pathology exhibiting overlapping features of both
