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( Nayoung Kim ),( Dong-hee Lee ),( Woo Seon Choi ),( Eunbi Yi ),( Hyojeong Kim ),( Jung Min Kim ),( Hyung-seung Jin ),( Hun Sik Kim ) 생화학분자생물학회(구 한국생화학분자생물학회) 2021 BMB Reports Vol.54 No.1
Natural killer (NK) cells, key antitumor effectors of the innate immune system, are endowed with the unique ability to spontaneously eliminate cells undergoing a neoplastic transformation. Given their broad reactivity against diverse types of cancer and close association with cancer prognosis, NK cells have gained considerable attention as a promising therapeutic target for cancer immunotherapy. NK cell-based therapies have demonstrated favorable clinical efficacies in several hematological malignancies but limited success in solid tumors, thus highlighting the need to develop new therapeutic strategies to restore and optimize anti-tumor activity while preventing tumor immune escape. The current therapeutic modalities yielding encouraging results in clinical trials include the blockade of immune checkpoint receptors to overcome the immune-evasion mechanism used by tumors and the incorporation of tumor-directed chimeric antigen receptors to enhance NK cell anti-tumor specificity and activity. These observations, together with recent advances in the understanding of NK cell activation within the tumor microenvironment, will facilitate the optimal design of NK cell-based therapy against a broad range of cancers and, more desirably, refractory cancers. [BMB Reports 2021; 54(1): 44-58]
Kim Hyung Seok,Na Min Jeong,Son Keun Hong,Yang Hee Doo,Kim Sang Yean,Shin Eunbi,Ha Jin Woong,Jeon Soyoung,Kang Keunsoo,Moon Kiho,Park Won Sang,Nam Suk Woo 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
Aberrant adenosine-to-inosine (A-to-I) RNA editing, catalyzed by adenosine deaminase acting on double-stranded RNA (ADAR), has been implicated in various cancers, but the mechanisms by which microRNA (miRNA) editing contributes to cancer development are largely unknown. Our multistage hepatocellular carcinogenesis transcriptome data analyses, together with publicly available data, indicated that ADAR1 was the most profoundly dysregulated gene among RNA-editing enzyme family members in liver cancer. Targeted inactivation of ADAR1 inhibited the in vitro tumorigenesis of liver cancer cells. An integrative computational analyses of RNA-edited hotspots and the known editing frequency of miRNAs suggested that the miRNA miR-3144-3p was edited by ADAR1 during liver cancer progression. Specifically, ADAR1 promoted A-to-I editing of canonical miR-3144-3p to replace the adenosine at Position 3 in the seed region with a guanine (ED_miR-3144-3p(3_A < G)) in liver cancer cells. We then demonstrated that Musashi RNA-binding protein 2 (MSI2) was a specific target of miR-3144-3p and that MSI2 overexpression was due to excessive ADAR1-dependent over-editing of canonical miR-3144-3p in liver cancer. In addition, target prediction analyses and validation experiments identified solute carrier family 38 member 4 (SLC38A4) as a specific gene target of ED_miR-3144-3p(3_A < G). The ectopic expression of both ADAR1 and the ED_miR-3144-3p(3_A < G) mimic enhanced mitotic activities, and ADAR1 suppressed SLC38A4 expression in liver cancer cells. Treatments with mouse-specific ADAR1-, MSI2-siRNA-, or SLC38A4-expressing plasmids suppressed tumorigenesis and tumor growth in a mouse model of spontaneous liver cancer. Our findings suggest that the aberrant regulation of ADAR1 augments oncogenic MSI2 effects by excessively editing canonical miR-3144-3p and that the resultant ED_miR-3144-3p(3_A < G) simultaneously suppresses tumor suppressor SLC38A4 expression, contributing to hepatocellular carcinogenesis.
Kim, Eunbi,Na, Sunghun,An, Borim,Yang, Se-Ran,Kim, Woo Jin,Ha, Kwon-Soo,Han, Eun-Taek,Park, Won Sun,Lee, Chang-Min,Lee, Ji Yoon,Lee, Seung-Joon,Hong, Seok-Ho The Korean Society of Pharmacology 2017 The Korean Journal of Physiology & Pharmacology Vol.21 No.2
Understanding the crosstalk mechanisms between perivascular cells (PVCs) and cancer cells might be beneficial in preventing cancer development and metastasis. In this study, we investigated the paracrine influence of PVCs derived from human umbilical cords on the proliferation of lung adenocarcinoma epithelial cells (A549) and erythroleukemia cells (TF-$1{\alpha}$ and K562) in vitro using $Transwell^{(R)}$ co-culture systems. PVCs promoted the proliferation of A549 cells without inducing morphological changes, but had no effect on the proliferation of TF-$1{\alpha}$ and K562 cells. To identify the factors secreted from PVCs, conditioned media harvested from PVC cultures were analyzed by antibody arrays. We identified a set of cytokines, including persephin (PSPN), a neurotrophic factor, and a key regulator of oral squamous cell carcinoma progression. Supplementation with PSPN significantly increased the proliferation of A549 cells. These results suggested that PVCs produced a differential effect on the proliferation of cancer cells in a cell-type dependent manner. Further, secretome analyses of PVCs and the elucidation of the molecular mechanisms could facilitate the discovery of therapeutic target(s) for lung cancer.
Expression of Ion Channels in Perivascular Stem Cells derived from Human Umbilical Cords
Kim, Eunbi,Park, Won Sun,Hong, Seok-Ho The Korean Society of Developmental Biology 2017 발생과 생식 Vol.21 No.1
Potassium channels, the largest group of pore proteins, selectively regulate the flow of potassium ($K^+$) ions across cell membranes. The activity and expression of $K^+$ channels are critical for the maintenance of normal functions in vessels and neurons, and for the regulation of cell differentiation and maturation. However, their role and expression in stem cells have been poorly understood. In this study, we isolated perivascular stem cells (PVCs) from human umbilical cords and investigated the expression patterns of big-conductance $Ca^{2+}$-activated $K^+$ ($BK_{Ca}$) and voltage-dependent $K^+$ ($K_v$) channels using the reverse transcription polymerase chain reaction. We also examined the effect of high glucose (HG, 25 mM) on expression levels of $BK_{Ca}$ and $K_v$ channels in PVCs. $K_{Ca}1.1$, $K_{Ca}{\beta}_3$, $K_v1.3$, $K_v3.2$, and $K_v6.1$ were detected in undifferentiated PVCs. In addition, HG treatment increased the amounts of $BK_{Ca}{\beta}_{3a}$, $BK_{Ca}{\beta}_4$, $K_v1.3$, $K_v1.6$, and $K_v6.1$ transcripts. These results suggested that ion channels may have important functions in the growth and differentiation of PVCs, which could be influenced by HG exposure.
Eunbi Kim,Sunghun Na,Borim An,Se-Ran Yang,Woo Jin Kim,Kwon-Soo Ha,Eun-Taek Han,Won Sun Park,Chang-Min Lee,Ji Yoon Lee,Seung-Joon Lee,Seok-Ho Hong 대한생리학회-대한약리학회 2017 The Korean Journal of Physiology & Pharmacology Vol.21 No.2
Understanding the crosstalk mechanisms between perivascular cells (PVCs) and cancer cells might be beneficial in preventing cancer development and metastasis. In this study, we investigated the paracrine influence of PVCs derived from human umbilical cords on the proliferation of lung adenocarcinoma epithelial cells (A549) and erythroleukemia cells (TF-1α and K562)<i> in vitro</i> using Transwell<sup>Ⓡ</sup> co-culture systems. PVCs promoted the proliferation of A549 cells without inducing morphological changes, but had no effect on the proliferation of TF-1α and K562 cells. To identify the factors secreted from PVCs, conditioned media harvested from PVC cultures were analyzed by antibody arrays. We identified a set of cytokines, including persephin (PSPN), a neurotrophic factor, and a key regulator of oral squamous cell carcinoma progression. Supplementation with PSPN significantly increased the proliferation of A549 cells. These results suggested that PVCs produced a differential effect on the proliferation of cancer cells in a cell-type dependent manner. Further, secretome analyses of PVCs and the elucidation of the molecular mechanisms could facilitate the discovery of therapeutic target(s) for lung cancer.
Expression of Ion Channels in Perivascular Stem Cells derived from Human Umbilical Cords
Eunbi Kim,Won Sun Park,Seok-Ho Hong 한국발생생물학회 2017 발생과 생식 Vol.21 No.1
Potassium channels, the largest group of pore proteins, selectively regulate the flow of potassium (K+) ions across cell membranes. The activity and expression of K+ channels are critical for the maintenance of normal functions in vessels and neurons, and for the regulation of cell differentiation and maturation. However, their role and expression in stem cells have been poorly understood. In this study, we isolated perivascular stem cells (PVCs) from human umbilical cords and investigated the expression patterns of big-conductance Ca2+-activated K+ (BKCa) and voltage-dependent K+ (Kv) channels using the reverse transcription polymerase chain reaction. We also examined the effect of high glucose (HG, 25 mM) on expression levels of BKCa and Kv channels in PVCs. KCa1.1, KCaβ3, Kv1.3, Kv3.2, and Kv6.1 were detected in undifferentiated PVCs. In addition, HG treatment increased the amounts of BKCaβ3a, BKCaβ4, Kv1.3, Kv1.6, and Kv6.1 transcripts. These results suggested that ion channels may have important functions in the growth and differentiation of PVCs, which could be influenced by HG exposure.