https://ir.ymlib.yonsei.ac.kr/handle/22282913/168904 2026-07-20T08:04:39Z 2026-07-20T08:04:39Z Lee, Dong Ki Oh, Jongwook Lee, Soyeon Huh, Hyunbin D. Sub, Yujin Yoon, Kuhn Shin, Woo Chul Kim, Sojin Park, Hyun Woo Gee, Heon Yung https://ir.ymlib.yonsei.ac.kr/handle/22282913/212947 2026-07-13T02:06:50Z 2026-07-01T00:00:00Z

Title: Adherent-to-suspension transition modulates circulating tumor cell dynamics and metastatic potential in melanoma Authors: Lee, Dong Ki; Oh, Jongwook; Lee, Soyeon; Huh, Hyunbin D.; Sub, Yujin; Yoon, Kuhn; Shin, Woo Chul; Kim, Sojin; Park, Hyun Woo; Gee, Heon Yung Abstract: Melanoma metastasis involves dynamic cellular reprogramming that enables tumor cells to survive detachment and disseminate to distant organs. We investigated the role of adherent-to-suspension transition (AST) in melanoma metastasis, examining its dynamics during metastatic dissemination and its relationship with epithelial-to-mesenchymal-like transition (EMT-like transition). Our findings reveal that AST genes, IKZF1, IRF8, and NFE2, critically modulate anchorage dependence through the regulation of cell adhesion and survival pathways. AST gene expression exhibits dynamic plasticity throughout the metastatic cascade, peaking in circulating tumor cells and reverting in established metastases. Clonal phylogenetic reconstruction reveals that AST-high circulating tumor cell clones possess enhanced metastatic capacity and dominate distant lesions. Notably, AST enhances metastatic capabilities and invasiveness in melanoma independently of EMT-like transition. Spatial analysis further indicated that AST-positive tumor cells preferentially localize near blood vessels, suggesting a facilitating role in blood-borne metastasis. These findings provide new insights into the mechanisms driving melanoma metastasis and highlight AST as a key factor contributing to tumor cell plasticity and dissemination. (c) 2026 The Author(s). Published by Elsevier Inc. on behalf of Korean Society for Molecular and Cellular Biology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

2026-07-01T00:00:00Z Cha, Seongho Jung, Myeongwoo Tak, Hyosun Ryu, Seungyeon Han, Sukyoung Chae, Dongwoo Kim, Jiyoon Jeong, Seung Min Kim, Wook Lee, Eun Kyung https://ir.ymlib.yonsei.ac.kr/handle/22282913/212930 2026-07-10T07:43:55Z 2026-06-01T00:00:00Z

Title: TIA-1 promotes FUNDC1-mediated mitophagy to protect against stress-induced cellular senescence Authors: Cha, Seongho; Jung, Myeongwoo; Tak, Hyosun; Ryu, Seungyeon; Han, Sukyoung; Chae, Dongwoo; Kim, Jiyoon; Jeong, Seung Min; Kim, Wook; Lee, Eun Kyung Abstract: Mitochondrial dysfunction, characterized by reduced mitophagy, excessive mitochondrial elongation, and elevated reactive oxygen species production, is a hallmark of cellular senescence. However, the molecular mechanisms linking impairment of redox balance to mitophagy suppression during senescence remain poorly understood. In this study, we identified TIA-1, an RNA-binding protein, as a positive regulator of FUNDC1 expression, a key receptor for ubiquitin-independent mitophagy. Sodium butyrate and ultraviolet-B irradiation triggered oxidative stress-associated senescence in HaCaT cells, leading to reduced TIA-1 expression, decreased FUNDC1 levels, impaired mitophagy flux, excessive mitochondrial elongation, and upregulation of senescence markers. Conversely, ectopic expression of TIA-1 restored FUNDC1 levels, enhanced mitophagy, improved mitochondrial function, and reduced senescence marker expression. Ribonucleoprotein immunoprecipitation assays confirmed that TIA-1 directly interacts with FUNDC1 mRNA, and subsequent analyses indicated that TIA-1 enhances FUNDC1 expression primarily through translational control. Together, these findings establish TIA-1 as a pivotal regulator of mitochondrial homeostasis during cellular stress, acting through FUNDC1 to sustain mitophagy and limit senescence. Targeting TIA-1 may offer new strategies to mitigate mitochondrial dysfunction and restore redox balance in aging and age-related diseases.

2026-06-01T00:00:00Z Kim, Haram Kang, Juwon Shin, Jeonghong Shin, Yujin Joo, Kye Il https://ir.ymlib.yonsei.ac.kr/handle/22282913/212967 2026-07-13T02:32:03Z 2026-06-01T00:00:00Z

Title: Cholesterol-tuned lipid nanoparticles for plasmid DNA delivery and CRISPR-Cas9 gene editing Authors: Kim, Haram; Kang, Juwon; Shin, Jeonghong; Shin, Yujin; Joo, Kye Il Abstract: Lipid nanoparticles (LNPs) have been extensively optimized for the cytoplasmic delivery of mRNA therapeutics, as evidenced by the clinical success of mRNA-based vaccines. However, the efficacy of LNPs for plasmid DNA delivery remains limited, because DNA must penetrate both the cellular membrane and the nuclear envelope to exert any therapeutic effect, which is an inherently more challenging intracellular trafficking requirement that current LNP formulations have not yet managed to resolve. Thus, this study aimed to systematically optimize the lipid composition of DNA-loaded LNPs (dLNPs) by varying the levels of cholesterol, ionizable lipid, and helper lipid across multiple formulations. Among the tested formulations, dLNP35-C56, comprising 35% ionizable lipid and 56% cholesterol, exhibited superior transfection efficiency, excellent serum stability, and favorable cytocompatibility, thereby identifying dLNP35-C56 as the optimal formulation for plasmid DNA delivery. To validate the therapeutic applicability, dLNP35-C56 was employed to deliver CRISPR-Cas9 components targeting the KRAS G12D oncogenic mutation, resulting in markedly enhanced mutation-selective editing efficiency and substantially reduced off-target editing in wild-type cells compared with conventional Lipofectamine-mediated delivery. These findings establish dLNP35-C56 as a potent and selective non-viral delivery platform for CRISPR-based cancer gene therapy.

2026-06-01T00:00:00Z Kim, Jinkyeong Lee, Seungjoon Hwang, Eunkyu Jung, Hwajin Lee, Chanhee Choi, Sang-Han Lee, Sooyeon Kim, Seongbin Moon, Heera Kim, Jisoo Lee, Gina Kim, Yong Gyu Shin, Soogeun Kang, Hyojin Kim, Se Jin Gee, Heon Yung Kim, Seong-Gi Lee, Eunee Kim, Eunjoon 신수근 https://ir.ymlib.yonsei.ac.kr/handle/22282913/212501 2026-06-10T06:30:39Z 2026-05-01T00:00:00Z

Title: Homozygous CHD8 mutation intensifies ASD phenotypes and attenuates sex differences Authors: Kim, Jinkyeong; Lee, Seungjoon; Hwang, Eunkyu; Jung, Hwajin; Lee, Chanhee; Choi, Sang-Han; Lee, Sooyeon; Kim, Seongbin; Moon, Heera; Kim, Jisoo; Lee, Gina; Kim, Yong Gyu; Shin, Soogeun; Kang, Hyojin; Kim, Se Jin; Gee, Heon Yung; Kim, Seong-Gi; Lee, Eunee; Kim, Eunjoon; 신수근 Abstract: CHD8 is a chromatin remodeler implicated in autism spectrum disorders (ASD) and multiple neurodevelopmental disorders, yet heterozygous Chd8-mutant mouse lines often exhibit only mild ASD-related phenotypes, leaving its role unclear. Because a complete knockout of Chd8 causes embryonic lethality, we generated viable homozygous Chd8-mutant mice carrying the human CHD8-Asn2373LysfsX2 mutation using a hybrid (C57BL6/J & times; 129/Sv) genetic background. Compared to heterozygous Chd8(+/N2373K) mice, the homozygous Chd8(N2373K/N2373K) mice showed more robust phenotypes, including increased ASD-related behaviors and brain volume, decreased cerebral blood volume/flow, brain rhythms, and synaptic transmission, and ASD-related transcriptomic changes. Notably, while Chd8(+/N2373K) mice on a pure background predominantly displayed behavioral deficits in males, the homozygous mutants in the hybrid background exhibited more pronounced female phenotypes, suggesting the interaction of genetic background and mutation strength. A direct comparison of Chd8(+/N2373K) and Chd8(N2373K/N2373K) mice on the same hybrid background across brain volume, cerebral blood flow, neuronal firing, synaptic transmission, and transcriptome revealed a gene dosage-dependent attenuation of sexual dimorphic phenotypes that varied by developmental stage and brain region. Transcriptomic analyses further implicated pathways related to synaptic function, RNA splicing, and mitochondrial activity in mediating differences in male-female protection and susceptibility. Thus, a homozygous Chd8 mutation not only intensifies ASD-related traits but can also diminish typical sex-specific severity patterns, uncovering a novel link between mutation strength and sexual dimorphism in ASD.

2026-05-01T00:00:00Z