Byung Chul Jung, Sung Hoon Kim, Yoonjung Cho, Yoon Suk Kim
Dysregulation of the E3 ubiquitin ligase Parkin has been linked to various human cancers, indicating that Parkin is a tumor suppressor protein. However, the mechanisms of action of Parkin remain unclear to date. Thus, we aimed to elucidate the mechanisms of action of Parkin as a tumor suppressor in human lung and colorectal cancer cells. Results showed that Parkin overexpression reduced the viability of A549 human lung cancer cells by inducing G2/M cell cycle arrest. In addition, Parkin caused DNA damage and ATM (Ataxia telangiectasia mutated) activation, which subsequently led to p53 activation...
September 8, 2023: BMB Reports
Ji Soo Kim, Seonha Lee, Won-Kon Kim, Baek-Soo Han
Mitochondrial transplantation is a promising therapeutic approach for the treatment of mitochondrial diseases caused by mutations in mitochondrial DNA, as well as several metabolic and neurological disorders. Animal studies have shown that mitochondrial transplantation can improve cellular energy metabolism, restore mitochondrial function, and prevent cell death. However, challenges need to be addressed, such as the delivery of functional mitochondria to the correct cells in the body, and the long-term stability and function of the transplanted mitochondria...
September 8, 2023: BMB Reports
Seungyeon Yang, Subin Moon, Soojung Claire Hur, Seung Min Jeong
Senescence, a cellular process through which damaged or dysfunctional cells suppress their cell cycle, contributes to aging or age-related functional declines. Cell metabolism has been closely correlated with aging processes and it is widely recognized that metabolic changes underlie cellular alterations with aging. Here, we report that fatty acid oxidation (FAO) serves as a critical regulator of cellular senescence and uncover the underlying mechanism by which FAO inhibition induces senescence. Pharmacological or genetic ablation of FAO results in a p53-dependent induction of cellular senescence in human fibroblasts, whereas enhancing FAO suppresses replicative senescence...
September 8, 2023: BMB Reports
Hyeran Shim, Kiwon Jang, Yeong Hak Bang, Hoang Bao Khanh Chu, Jisun Kang, Jin-Young Lee, Sheehyun Cho, Hong Seok Lee, Jongbum Jeon, Taeyeon Hwang, Soobok Joe, Jinyeong Lim, Ji-Hye Choi, Eun Hye Joo, Kyunghee Park, Ji Hwan Moon, Kyung Yeon Han, Yourae Hong, Woo Yong Lee, Hee Cheol Kim, Seong Hyeon Yun, Yong Beom Cho, Yoon Ah Park, Jung Wook Huh, Jung Kyong Shin, Dae Hee Pyo, Hyekyung Hong, Hae-Ock Lee, Woong-Yang Park, Jin Ok Yang, Young-Joon Kim
Alterations in DNA methylation play an important pathophysiological role in the development and progression of colorectal cancer. We comprehensively profiled DNA methylation alterations in 165 Korean patients with colorectal cancer (CRC), and conducted an in-depth investigation of cancer-specific methylation patterns. Our analysis of the tumor samples revealed a significant presence of hypomethylated probes, primarily within the gene body regions; few hypermethylated sites were observed, which were mostly enriched in promoter-like and CpG island regions...
August 22, 2023: BMB Reports
Seok-Byung Lim, Soobok Joe, Hyo-Ju Kim, Jong Lyul Lee, In Ja Park, Yong Sik Yoon, Chan Wook Kim, Jong-Hwan Kim, Sangok Kim, Jin-Young Lee, Hyeran Shim, Hoang Bao Khanh Chu, Sheehyun Cho, Jisun Kang, Si-Cho Kim, Hong Seok Lee, Young-Joon Kim, Seon-Young Kim, Chang Sik Yu
Aberrant DNA methylation plays a pivotal role in the onset and progression of colorectal cancer (CRC), a disease with high incidence and mortality rates in Korea. Several CRC-associated diagnostic and prognostic methylation markers have been identified; however, due to a lack of comprehensive clinical and methylome data, these markers have not been validated in the Korean population. Therefore, in this study, we aimed to obtain the CRC methylation profile using 172 tumors and 128 adjacent normal colon tissues of Korean patients with CRC...
August 22, 2023: BMB Reports
Jaehong Park, Dong-Hyun Lee
Most cancer cells utilize glucose at a high rate to produce energy and precursors for the biosynthesis of macromolecules such as lipids, proteins, and nucleic acids. This phenomenon is called the Warburg effect or aerobic glycolysis- this distinct characteristic is an attractive target for developing anticancer drugs. Here, we found that Phosphofructokinase-1 (PFK-1) is a substrate of the Protein Phosphatase 4 catalytic subunit (PP4C)/PP4 regulatory subunit 1 (PP4R1) complex by using immunoprecipitation and in vitro assay...
August 22, 2023: BMB Reports
Sung-Hoon Lee, Shin-Young Park, Jung Ha Kim, Nacksung Kim, Junwon Lee
Ginsenosides, among the most active components of ginseng, exhibit several therapeutic effects against cancer, diabetes, and other metabolic diseases. However, the molecular mechanism underlying the anti-osteoporotic activity of ginsenoside Rg2, a major ginsenoside, has not been clearly elucidated. This study aimed to determine the effects of ginsenoside Rg2 on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation. Results indicate that ginsenoside Rg2 inhibits RANKL-induced osteoclast differentiation of bone marrow macrophages (BMMs) without cytotoxicity...
August 22, 2023: BMB Reports
Hyunji Park, Na-Young Park, Ara Koh
The gut microbiome is widely recognized as a dynamic organ with a profound influence on human physiology and pathology. Extensive epidemiological and longitudinal cohort studies have provided compelling evidence that disruptions in the early-life microbiome can have long-lasting health implications. Various factors before, during, and after birth contribute to shaping the composition and function of the neonatal and infant microbiome. While these alterations can be partially restored over time, metabolic phenotypes may persist, necessitating research to identify the critical period for early intervention to achieve phenotypic recovery beyond microbiome composition...
August 22, 2023: BMB Reports
Soobok Joe, Jinyong Kim, Jin-Young Lee, Jongbum Jeon, Iksu Byeon, Sae-Won Han, Seung-Bum Ryoo, Kyu Joo Park, Sheehyun Cho, Hyeran Shim, Hoang Bao Khanh Chu, Jisun Kang, Hong Seok Lee, DongWoo Kim, Young-Joon Kim, Tae-You Kim, Seon-Young Kim
DNA methylation regulates gene expression and contributes to tumorigenesis in the early stages of cancer. In colorectal cancer (CRC), CpG island methylator phenotype (CIMP) is recognized as a distinct subset that is associated with specific molecular and clinical features. In this study, we investigated the genome-wide DNA methylation patterns among patients with CRC. The methylation data of 1 unmatched normal, 142 adjacent normal, and 294 tumor samples were analyzed. We identified 40,003 differentially methylated positions with 6,933 (79...
August 14, 2023: BMB Reports
Inyoung Kim, Taeho Park, Ji-Yoon Noh, Wantae Kim
In various organisms, the Hippo signaling pathway has been identified as a master regulator of organ size determination and tissue homeostasis. The Hippo signaling coordinates embryonic development, tissue regeneration and differentiation, through regulating cell proliferation and survival. The YAP and TAZ (YAP/TAZ) act as core transducers of the Hippo pathway, and they are tightly and exquisitely regulated in response to various intrinsic and extrinsic stimuli. Abnormal regulation or genetic variation of the Hippo pathway causes a wide range of human diseases, including cancer...
August 14, 2023: BMB Reports
Cheong-Whan Chae, Gun Choi, You Ji Kim, Mingug Cho, Yoo-Wook Kwon, Hyo-Soo Kim
Hematopoiesis is regulated by crosstalk between long-term repopulating hematopoietic stem cells (LT-HSCs) and supporting niche cells in the bone marrow (BM). Here, we describe the role of KAI1, which is mainly expressed on LT-HSCs and rarely on other hematopoietic stem-progenitor cells (HSPCs), in nichemediated LT-HSC maintenance. KAI1 activates TGF-β1/Smad3 signal in LT-HSCs, leading to the induction of CDK inhibitors and inhibition of the cell cycle. The KAI1-binding partner DARC is expressed on macrophages and stabilizes KAI1 on LT-HSCs, promoting their quiescence...
August 14, 2023: BMB Reports
Xianyu Piao, Jung-Woo Kim, Moonjung Hyun, Zhao Wang, Suk-Gyun Park, In A Cho, Je-Hwang Ryu, Bin-Na Lee, Ju Han Song, Jeong-Tae Koh
Osteoporosis is a major public health concern, which requires novel therapeutic strategies to prevent or mitigate bone loss. Natural compounds have attracted attention as potential therapeutic agents due to their safety and efficacy. In this study, we investigated the regulatory activities of boeravinone B (BOB), a natural rotenoid isolated from the medicinal plant Boerhavia diffusa, on the differentiation of osteoclasts and mesenchymal stem cells (MSCs), the two main cell components responsible for bone remodeling...
August 14, 2023: BMB Reports
Sang Hyeon Ju, Hyon-Seung Yi
Muscle wasting in end-stage renal disease (ESRD) is an escalating issue due to the increasing global prevalence of ESRD and its significant clinical impact, including a close association with elevated mortality risk. The phenomenon of muscle wasting in ESRD, which exceeds the rate of muscle loss observed in the normal aging process, arises from multifactorial processes. This review paper aims to provide a comprehensive understanding of muscle wasting in ESRD, covering its epidemiology, underlying molecular mechanisms, and current and emerging therapeutic interventions...
July 24, 2023: BMB Reports
Jeong-Hoon Hahm, Hyo-Deok Seo, Chang Hwa Jung, Jiyun Ahn
The share of the population that is aging is growing rapidly. In an aging society, technologies and interventions that delay the aging process are of great interest. Dietary restriction (DR) is the most reproducible and effective nutritional intervention tested to date for delaying the aging process and prolonging the health span in animal models. Preventive effects of DR on age-related diseases have also been reported in human. In addition, highly conserved signaling pathways from small animal models to human mediate the effects of DR...
July 24, 2023: BMB Reports
Hyun Ha Park, Byeong-Hyeon Kim, Seol Hwa Leem, Yong Ho Park, Hyang-Sook Hoe, Yunkwon Nam, Sujin Kim, Soo Jung Shin, Minho Moon
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline. Several recent studies demonstrated that impaired adult neurogenesis could contribute to AD-related cognitive impairment. Adult subventricular zone (SVZ) neurogenesis, which occurs in the lateral ventricles, plays a crucial role in structural plasticity and neural circuit maintenance. Alterations in adult SVZ neurogenesis are early events in AD, and impaired adult neurogenesis is influenced by the accumulation of intracellular Aβ...
July 24, 2023: BMB Reports
Dan Zhou, Hae Chan Ha, Goowon Yang, Ji Min Jang, Bo Kyung Park, Zhicheng Fu, In Chul Shin, Dae Kyong Kim
The development of atherosclerotic cardiovascular disease is associated with the phenotypic switching of vascular smooth muscle cells (SMCs) from a contractile to a synthetic state, leading to cell migration and proliferation. Platelet‑derived growth factor‑BB (PDGF‑BB) modulates this de-differentiation by initiating a number of biological processes. In this study, we show that gene expression of hyaluronic acid (HA) and proteoglycan link protein 1 (HAPLN1) was upregulated during differentiation of human aortic SMCs (HASMCs) into a contractile state, but downregulated upon during PDGF-BB-induced dedifferentiation...
July 4, 2023: BMB Reports
Mi Yea Lee, Min-Jee Kim, Jun-O Jin, Peter Chang-Whan Lee
Deubiquitinases (DUBs) are an essential component of the ubiquitin-proteasome system (UPS). They trim ubiquitin from substrate proteins, thereby preventing them from degradation, and modulate different cellular processes. Ubiquitin-specific protease 14 (USP14) is a DUB that has mainly been studied for its role in tumorigenesis in several cancers. In the present study, we found that the protein levels of USP14 were remarkably higher in gastric cancer tissues than in the adjacent normal tissues. We also demonstrated that the inhibition of USP14 activity using IU1 (an USP14 inhibitor) or the inhibition of USP14 expression using USP14-specific siRNA markedly reduced the viability of gastric cancer cells and suppressed their migratory and invasive abilities...
July 4, 2023: BMB Reports
So Mi Yang, Jueun Kim, Ji-Yeon Lee, Jung-Shin Lee, Ji Min Lee
Intrahepatic cholangiocarcinoma (ICC) is one of the bile duct cancers and a rare malignant tumor with a poor prognosis owing to a lack of early diagnosis and resistance to conventional chemotherapy. A combination of gemcitabine and cisplatin is a treatment approach typically being attempted for the first line. However, its underlying mechanism of resistance to chemotherapy is poorly understood. We addressed this by studying the dynamics in the human ICC SCK cell line. Here, we report that the regulation of glucose and glutamine metabolism is a key factor in overcoming cisplatin resistance of SCK...
July 4, 2023: BMB Reports
Jungwhoi Lee, Jungsul Lee, Woo Gwang Sim, Jae-Hoon Kim, Chulhee Choi, Jongwook Jeon
A number of therapeutic drugs have been developed from functional chemicals found in plants. Knowledge of plants used for medicinal purposes has historically been transmitted by word of mouth or through literature. The aim of the present study is to provide a systemic platform for the development of lead compounds against breast cancer based on a traditional medical text. To verify our systematic approach, integrating processes consisted of text mining of traditional medical texts, 3-D virtual docking screening, and in vitro and in vivo experimental validations were demonstrated...
June 26, 2023: BMB Reports
Sangsoo Lee, Haesoo Jung, Sunkyung Choi, Namjoon Cho, Eun-Mi Kim, Kee K Kim
Methyltransferase-like 3 (METTL3), a key component of the m6A methyltransferase complex, regulates the splicing, nuclear transport, stability, and translation of its target genes. However, the mechanism underlying the regulation of METTL3 expression by alternative splicing (AS) remains unknown. We analyzed the expression pattern of METTL3 after AS in human tissues and confirmed the expression of an isoform retaining introns 8 and 9 (METTL3-IR). We confirmed the different intracellular localizations of METTL3-IR and METTL3 proteins using immunofluorescence microscopy...
June 26, 2023: BMB Reports
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