https://scholar.korea.ac.kr/handle/2021.sw.korea/2677 2026-04-05T16:02:54Z https://scholar.korea.ac.kr/handle/2021.sw.korea/268498 Title: MicroRNA-induced reprogramming of tumor-associated macrophages for modulation of tumor immune microenvironment Authors: Wu, Yina; Park, Jinwon; Xu, Enzhen; Kim, Dongyoon; Oh, Yu-Kyoung; Lee, Jaiwoo Abstract: Tumor-associated macrophages (TAMs) are abundant in the tumor microenvironment and typically exhibit pro- tumoral phenotypes. TAMs overexpress the signal regulatory protein alpha (SIRP alpha) receptor on their surface, which interacts with CD47 on tumor cells to inhibit their phagocytic activity. In this study, we developed lipid nanoparticles modified with an anti-SIRP alpha antibody (aSIRP alpha) for the targeted delivery of microRNA-155 (miR155@aSIRP alpha-LNP) to TAMs, aiming to enhance their anti-tumoral phenotypes within the tumor microenvironment. The aSIRP alpha modification not only facilitated nanoparticle uptake by TAMs rather than B16F10 cells, but also blocked the anti-phagocytosis signal by disrupting the interaction between SIRP alpha and CD47 on cancer cells. This dual functionality enhanced the expression of anti-tumoral phenotype markers in TAMs and activated macrophage-mediated phagocytosis of tumor cells. In a melanoma model, intratumoral administration of miR155@aSIRP alpha-LNP to B16F10 tumor-bearing mice reprogrammed TAMs toward anti-tumoral phenotypes. The anti-tumoral cytokines released by these TAMs remodeled the immunosuppressive tumor microenvironment, increasing cytotoxic T cell infiltration and reducing the regulatory T cell population, inhibiting tumor progression. This approach indicates the potential of miRNA-based therapies to overcome the limitations of current immunotherapies in treating cold solid tumors. Overall, the results suggest that delivering miR155 to TAMs by targeting SIRP alpha is a promising strategy for modulating the immunosuppressive tumor microenvironment in cancer immunotherapy. 2025-05-10T00:00:00Z https://scholar.korea.ac.kr/handle/2021.sw.korea/269327 Title: An eRNA transcription checkpoint for diverse signal-dependent enhancer activation programs Authors: Wang, Lishuan; Yuan, Wei; Gamliel, Amir; Ma, Wubin; Lee, Seowon; Tan, Yuliang; Chen, Zeyu; Taylor, Havilah; Ohgi, Kenneth; Oh, Soohwan; Aggarwal, Aneel K.; Rosenfeld, Michael G. Abstract: The evidence that signal- and ligand-dependent pathways function by activating regulatory enhancer programs suggests that a 'checkpoint' strategy may underline activation of many diversely regulated enhancers. Here we report a molecular mechanism common to several acute signal- and ligand-dependent enhancer activation programs based on release of a shared enhancer RNA (eRNA) transcription checkpoint. It requires recruitment of a DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-phosphorylated RING finger repressor (Kr & uuml;ppel-associated box)-associated protein 1 (KAP1) as a modulator, inhibiting its association with 7SK and E3 small ubiquitin-like modifier (SUMO) ligase activity on the CDK9 subunit of positive transcription elongation factor b (P-TEFb). This facilitates formation of an activated P-TEFb complex, licensing eRNA elongation. Overcoming this checkpoint for signal-dependent enhancer activation occurs in diverse pathways, including estrogen receptor-alpha, NF-kappa B-regulated proinflammatory stimulation, androgen receptor and neuronal depolarization. Therefore, a specific strategy required to convert a basal state enhancer P-TEFb complex to an active state to release a conserved checkpoint is apparently employed by several functionally important signal-regulated regulatory enhancers to implement the instructions of the endocrine and paracrine system. 2025-04-01T00:00:00Z https://scholar.korea.ac.kr/handle/2021.sw.korea/272687 Title: DNA Nanotechnology Authors: Jaiwoo Lee 2025-04-01T00:00:00Z https://scholar.korea.ac.kr/handle/2021.sw.korea/268193 Title: Neurological Adverse Events Associated with the Use of Janus Kinase Inhibitors: A Pharmacovigilance Study Based on Vigibase Authors: Park, Sunny; Kim, Min Kyu; Park, Sung Bin; Kim, Dong Hyeok; Byun, Young Joo; Choi, Soo An Abstract: Background: Janus kinase (JAK) inhibitors are a new class of targeted therapies that block cytokines and the signal transduction and activators of transcription (STAT) pathway. However, post-marketing surveillance studies have led to revised recommendations, highlighting potential serious heart-related events and cancer risk of JAK inhibitors. Here, we aimed to determine the neurological adverse events (AEs) of JAK inhibitors (tofacitinib, ruxolitinib, and baricitinib) based on a global real-world database. Methods: We analyzed individual case safety reports from the Uppsala Monitoring Center from January 1968 to 4 April 2022. A disproportionality analysis was performed using the proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC) to detect signals. Signals were classified according to the hierarchy of the Medical Dictionary for Regulatory Activities (MedDRA). Additionally, a stratified disproportionality analysis by age group and sex was performed for major AEs. Results: A total of 30,051,159 reports for all drugs were analyzed in this study. Among 105,798 reports of tofacitinib, 14.1% (14,863 reports) were neurological AEs. For ruxolitinib and baricitinib, 14.5% (6317 reports) and 10.2% (1216 reports) were neurological AEs, respectively. Various neurological AE signals were detected for tofacitinib and ruxolitinib, with memory impairment exhibiting the highest number of reports and a positive signal in the stratified disproportionality analysis by age group. Baricitinib did not reach the signal detection threshold. Conclusions: This study suggests the potential for neurological AEs, including memory impairment, associated with tofacitinib and ruxolitinib use based on a real-world database. 2025-03-11T00:00:00Z