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Journal Exp. Mol. Med.

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The RCAN1.4-calcineurin/NFAT signaling pathway is essential for hypoxic adaption of intervertebral discs.

Bao Huang, Yongqing He, Shengwen Li, Xiaoan Wei, Junhui Liu, Zhi Shan, Yue Huang, Jian Chen, Fengdong Zhao,

Calcipressin-1, also known as regulator of calcineurin 1 (RCAN1), can specifically bind calcineurin at or near the calcineurin A catalytic domain and downregulate calcineurin activity. However, whether RCAN1 affects the hypoxic intervertebral disc (IVD) phenotype through the calcineurin/NFAT signaling pathway remains unclear. First, we confirmed the characteristics of the degenerative ... Read more >>

Exp. Mol. Med. (Experimental & molecular medicine)
[2020, :]

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Endothelial-to-mesenchymal transition in anticancer therapy and normal tissue damage.

Kyu Jin Choi, Jae-Kyung Nam, Ji-Hee Kim, Seo-Hyun Choi, Yoon-Jin Lee,

Endothelial-to-mesenchymal transition (EndMT) involves the phenotypic conversion of endothelial-to-mesenchymal cells, and was first discovered in association with embryonic heart development. EndMT can regulate various processes, such as tissue fibrosis and cancer. Recent findings have shown that EndMT is related to resistance to cancer therapy, such as chemotherapy, antiangiogenic therapy, and ... Read more >>

Exp. Mol. Med. (Experimental & molecular medicine)
[2020, :]

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Recent advances of sterile inflammation and inter-organ cross-talk in alcoholic liver disease.

Young-Ri Shim, Won-Il Jeong,

Alcoholic liver disease (ALD) is one of the fastest-growing concerns worldwide. In addition to bacterial endotoxins in the portal circulation, recent lines of evidence have suggested that sterile inflammation caused by a wide range of stimuli induces alcoholic liver injury, in which damage-associated molecular patterns (DAMPs) play critical roles in ... Read more >>

Exp. Mol. Med. (Experimental & molecular medicine)
[2020, :]

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Amplification of transglutaminase 2 enhances tumor-promoting inflammation in gastric cancers.

Sung-Yup Cho, Yumi Oh, Eui Man Jeong, Sanghui Park, Dakeun Lee, Xiaorui Wang, Qiqi Zeng, Hongyu Qin, Fang Hu, Hui Gong, Xi Liu, Guanjun Zhang, Deukchae Na, Jieun Lee, Jeesoo Chae, Yun-Suhk Suh, Seong-Ho Kong, Hyuk-Joon Lee, Jong-Il Kim, Hansoo Park, Chengsheng Zhang, Han-Kwang Yang, Charles Lee,

Tumor-promoting inflammation is a hallmark of cancer and is highly associated with tumor progression, angiogenesis, and metastasis. Tumor-associated macrophages (TAMs) are major drivers of tumor-promoting inflammation, but due to the complexity of the tumor microenvironment, the detailed regulatory mechanisms are still under investigation. Here, we investigated a novel role for ... Read more >>

Exp. Mol. Med. (Experimental & molecular medicine)
[2020, :]

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Angiogenic cytokines can reflect the synovitis severity and treatment response to biologics in rheumatoid arthritis.

Ji-Won Kim, Jin-Sun Kong, Saseong Lee, Seung-Ah Yoo, Jung Hee Koh, Jingchun Jin, Wan-Uk Kim,

Angiogenesis and synoviocyte hyperplasia, called 'pannus,' are pathologic hallmarks of rheumatoid arthritis (RA). To determine the clinical significance of angiogenic cytokines in RA, the levels of pro-angiogenic cytokines, including VEGF, placenta growth factor (PlGF), and IL-6, were measured in the synovial fluid (SF, n = 54) and sera of RA patients (n = 157) ... Read more >>

Exp. Mol. Med. (Experimental & molecular medicine)
[2020, :]

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Destabilization of β-catenin and RAS by targeting the Wnt/β-catenin pathway as a potential treatment for triple-negative breast cancer.

Won-Ji Ryu, Jeong Dong Lee, Jong-Chan Park, Pu-Hyeon Cha, Yong-Hee Cho, Jee Ye Kim, Joo Hyuk Sohn, Soonmyung Paik, Kang-Yell Choi,

Triple-negative breast cancer (TNBC) is a severe and heterogeneous disease that lacks an approved targeted therapy and has a poor clinical outcome to chemotherapy. Although the RAS-ERK signaling axis is rarely mutated in TNBC, ~50% of TNBCs show an increased copy number and overexpression of epidermal growth factor receptor (EGFR). ... Read more >>

Exp. Mol. Med. (Experimental & molecular medicine)
[2020, :]

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Gene expression regulation by CDK12: a versatile kinase in cancer with functions beyond CTD phosphorylation.

Seung Hyuk Choi, Seongjae Kim, Katherine A Jones,

Cyclin-dependent kinases (CDKs) play critical roles in cell cycle progression and gene expression regulation. In human cancer, transcription-associated CDKs can activate oncogenic gene expression programs, whereas cell cycle-regulatory CDKs mainly induce uncontrolled proliferation. Cyclin-dependent kinase 12 (CDK12) belongs to the CDK family of serine/threonine kinases and has been recently found ... Read more >>

Exp. Mol. Med. (Experimental & molecular medicine)
[2020, :]

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Recent insights of T cell receptor-mediated signaling pathways for T cell activation and development.

Jeong-Ryul Hwang, Yeongseon Byeon, Donghwan Kim, Sung-Gyoo Park,

T cell activation requires extracellular stimulatory signals that are mainly mediated by T cell receptor (TCR) complexes. The TCR recognizes antigens on major histocompatibility complex molecules with the cooperation of CD4 or CD8 coreceptors. After recognition, TCR-induced signaling cascades that propagate signals via various molecules and second messengers are induced. ... Read more >>

Exp. Mol. Med. (Experimental & molecular medicine)
[2020, :]

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The FBW7-MCL-1 axis is key in M1 and M2 macrophage-related colon cancer cell progression: validating the immunotherapeutic value of targeting PI3Kγ.

Yeo Song Lee, Su Jeong Song, Hye Kyung Hong, Bo Young Oh, Woo Yong Lee, Yong Beom Cho,

Colorectal cancer is a devastating disease with a low 5-year survival rate. Recently, many researchers have studied the mechanisms of tumor progression related to the tumor microenvironment. Here, we addressed the prognostic value of tumor-associated macrophages (TAMs) using a total of 232 CRC patient tissue samples and investigated the mechanisms ... Read more >>

Exp. Mol. Med. (Experimental & molecular medicine)
[2020, :]

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MAPS-seq: magnetic bead-assisted parallel single-cell gene expression profiling.

Munsu Park, Dongin Lee, Duhee Bang, Ji Hyun Lee,

Recently developed single-cell RNA sequencing methods allow the simultaneous profiling of the transcriptomes of thousands of individual cells. However, current methods still require advanced equipment or entail substantial waste of reagents. Here, we introduce magnetic bead-assisted parallel single-cell gene expression sequencing (MAPS-seq), a microwell-based method that pools samples before the ... Read more >>

Exp. Mol. Med. (Experimental & molecular medicine)
[2020, :]

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Oncogenic super-enhancer formation in tumorigenesis and its molecular mechanisms.

Qunying Jia, Shuhua Chen, Yuan Tan, Yuejin Li, Faqing Tang,

Super-enhancers (SEs) consist of a cluster of many enhancers bound to a great number of transcription factors. They are critical cis-regulatory elements that determine the identity of various human cell types. During tumorigenesis, DNA mutations and indels, chromosomal rearrangements, three-dimensional chromatin structural changes, and viral infections mediate oncogenic SE activation, ... Read more >>

Exp. Mol. Med. (Experimental & molecular medicine)
[2020, :]

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Molecular cross talk among the components of the regulatory machinery of mitochondrial structure and quality control.

Hyo Min Cho, Woong Sun,

Mitochondrial dysfunction critically impairs cellular health and often causes or affects the progression of several diseases, including neurodegenerative diseases and cancer. Thus, cells must have several ways to monitor the condition of mitochondrial quality and maintain mitochondrial health. Accumulating evidence suggests that the molecular machinery responding to spontaneous changes in ... Read more >>

Exp. Mol. Med. (Experimental & molecular medicine)
[2020, :]

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Diverse molecular functions of m6A mRNA modification in cancer.

Seung Hun Han, Junho Choe,

N6-methyladenosine (m6A), the most prevalent chemical modification found on eukaryotic mRNA, is associated with almost all stages of mRNA metabolism and influences various human diseases. Recent research has implicated the aberrant regulation of m6A mRNA modification in many human cancers. An increasing number of studies have revealed that dysregulation of ... Read more >>

Exp. Mol. Med. (Experimental & molecular medicine)
[2020, :]

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Neural regulation of energy and bone homeostasis by the synaptic adhesion molecule Calsyntenin-3.

Sung-Jin Kim, Yong Taek Jeong, Se Rok Jeong, Munsu Park, Hye Sun Go, Mi Young Kim, Je Kyung Seong, Ki Woo Kim, Jeong Taeg Seo, Chul Hoon Kim, Ji Hyun Lee, Seok Jun Moon,

Neuronal regulation of energy and bone metabolism is important for body homeostasis. Many studies have emphasized the importance of synaptic adhesion molecules in the formation of synapses, but their roles in physiology still await further characterization. Here, we found that the synaptic adhesion molecule Calsyntenin-3 (CLSTN3) regulates energy and bone ... Read more >>

Exp. Mol. Med. (Experimental & molecular medicine)
[2020, :]

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The cellular function of SCAP in metabolic signaling.

Sun Hee Lee, Jae-Ho Lee, Seung-Soon Im,

Sterol regulatory element binding protein (SREBP) cleavage activating protein (SCAP) is a key regulator of SREBP maturation. SCAP induces translocation of SREBP from the endoplasmic reticulum to the Golgi apparatus, allowing it to regulate cellular triglyceride and cholesterol levels. Previous studies have shown that suppression of SREBP activation in SCAP ... Read more >>

Exp. Mol. Med. (Experimental & molecular medicine)
[2020, :]

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Protective role of endothelial calpain knockout in lipopolysaccharide-induced acute kidney injury via attenuation of the p38-iNOS pathway and NO/ROS production.

Zhifeng Liu, Jingjing Ji, Dong Zheng, Lei Su, Tianqing Peng, Jing Tang,

To explore the role of calpain and its signaling pathway in lipopolysaccharide (LPS)-induced acute kidney injury (AKI), animal models of endotoxemia were established by administration of LPS to mice with endothelial-specific Capn4 knockout (TEK/Capn4-/-), mice with calpastatin (an endogenous calpain inhibitor) overexpression (Tg-CAST) and mice with myeloid-specific Capn4 knockout (LYZ/Capn4-/-). ... Read more >>

Exp. Mol. Med. (Experimental & molecular medicine)
[2020, 52(4):702-712]

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Pathogenic diversity of RNA variants and RNA variation-associated factors in cancer development.

Hee Doo Yang, Suk Woo Nam,

Recently, with the development of RNA sequencing technologies such as next-generation sequencing (NGS) for RNA, numerous variations of alternatively processed RNAs made by alternative splicing, RNA editing, alternative maturation of microRNA (miRNA), RNA methylation, and alternative polyadenylation have been uncovered. Furthermore, abnormally processed RNAs can cause a variety of diseases, ... Read more >>

Exp. Mol. Med. (Experimental & molecular medicine)
[2020, 52(4):582-593]

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The interdependence of mammary-specific super-enhancers and their native promoters facilitates gene activation during pregnancy.

Xianke Zeng, Hye Kyung Lee, Chaochen Wang, Precious Achikeh, Chengyu Liu, Lothar Hennighausen,

Lineage-specific genetic programs rely on cell-restricted super-enhancers, which are platforms for high-density transcription factor occupation. It is not known whether super-enhancers synergize specifically with their native promoters or provide autonomous and independent regulatory platforms. Here, we investigated the ability of the mammary Wap super-enhancer to activate the promoter of the ... Read more >>

Exp. Mol. Med. (Experimental & molecular medicine)
[2020, 52(4):682-690]

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Spi-C positively regulates RANKL-mediated osteoclast differentiation and function.

Eun Mi Go, Ju Hee Oh, Jin Hee Park, Soo Young Lee, Na Kyung Lee,

Spi-C is an SPI-group erythroblast transformation-specific domain transcription factor expressed during B-cell development. Here, we report that Spi-C is a novel receptor activator of nuclear factor-κB ligand (RANKL)-inducible protein that positively regulates RANKL-mediated osteoclast differentiation and function. Knockdown of Spi-C decreased the expression of RANKL-induced nuclear factor of activated T-cells, ... Read more >>

Exp. Mol. Med. (Experimental & molecular medicine)
[2020, 52(4):691-701]

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Differentiation of adipose-derived stem cells into functional chondrocytes by a small molecule that induces Sox9.

Jiyun Lee, Chang Youn Lee, Jun-Hee Park, Hyang-Hee Seo, Sunhye Shin, Byeong-Wook Song, Il-Kwon Kim, Sang Woo Kim, Seahyoung Lee, Jong-Chul Park, Soyeon Lim, Ki-Chul Hwang,

Osteoarthritis (OA) is a common joint disease that results from the disintegration of joint cartilage and the underlying bone. Because cartilage and chondrocytes lack the ability to self-regenerate, efforts have been made to utilize stem cells to treat OA. Although various methods have been used to differentiate stem cells into ... Read more >>

Exp. Mol. Med. (Experimental & molecular medicine)
[2020, 52(4):672-681]

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The force awakens: metastatic dormant cancer cells.

So-Yeon Park, Jeong-Seok Nam,

Recurrent cancer that spreads to distant sites is the leading cause of disease-related death among cancer patients. Cancer cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. These dormant cancer cells (DCCs) are rarely detectable with current diagnostic systems. Moreover, they ... Read more >>

Exp. Mol. Med. (Experimental & molecular medicine)
[2020, 52(4):569-581]

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Peroxisome proliferator-activated receptor gamma as a theragnostic target for mesenchymal-type glioblastoma patients.

Tuyen N M Hua, Jiwoong Oh, Sohyun Kim, Jayson M Antonio, Vu T A Vo, Jiyeon Om, Jong-Whan Choi, Jeong-Yub Kim, Chan-Woong Jung, Myung-Jin Park, Yangsik Jeong,

Glioblastomas (GBMs) are characterized by four subtypes, proneural (PN), neural, classical, and mesenchymal (MES) GBMs, and they all have distinct activated signaling pathways. Among the subtypes, PN and MES GBMs show mutually exclusive genetic signatures, and the MES phenotype is, in general, believed to be associated with more aggressive features ... Read more >>

Exp. Mol. Med. (Experimental & molecular medicine)
[2020, 52(4):629-642]

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Dysregulation of the EphrinB2-EphB4 ratio in pediatric cerebral arteriovenous malformations is associated with endothelial cell dysfunction in vitro and functions as a novel noninvasive biomarker in patients.

Katie Pricola Fehnel, David L Penn, Micah Duggins-Warf, Maxwell Gruber, Steven Pineda, Julie Sesen, Alexander Moses-Gardner, Nishali Shah, Jessica Driscoll, David Zurakowski, Darren B Orbach, Edward R Smith,

We investigated (1) EphrinB2 and EphB4 receptor expression in cerebral AVMs, (2) the impact of an altered EphrinB2:EphB4 ratio on brain endothelial cell function and (3) potential translational applications of these data. The following parameters were compared between AVM endothelial cells (AVMECs) and human brain microvascular endothelial cells (HBMVECs): quantified ... Read more >>

Exp. Mol. Med. (Experimental & molecular medicine)
[2020, 52(4):658-671]

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New fluid biomarkers tracking non-amyloid-β and non-tau pathology in Alzheimer's disease.

Sun Ah Park, Song Mi Han, Chae Eun Kim,

Cerebrospinal fluid (CSF) biomarkers based on the core pathological proteins associated with Alzheimer's disease (AD), i.e., amyloid-β (Aβ) and tau protein, are widely regarded as useful diagnostic biomarkers. However, a lack of biomarkers for monitoring the treatment response and indexing clinical severity has proven to be problematic in drug trials ... Read more >>

Exp. Mol. Med. (Experimental & molecular medicine)
[2020, 52(4):556-568]

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The cGAS/STING/TBK1/IRF3 innate immunity pathway maintains chromosomal stability through regulation of p21 levels.

Abdul Basit, Min-Guk Cho, Eui-Yun Kim, Dohyeong Kwon, Suk-Jo Kang, Jae-Ho Lee,

Chromosomal instability (CIN) in cancer cells has been reported to activate the cGAS-STING innate immunity pathway via micronuclei formation, thus affecting tumor immunity and tumor progression. However, adverse effects of the cGAS/STING pathway as they relate to CIN have not yet been investigated. We addressed this issue using knockdown and ... Read more >>

Exp. Mol. Med. (Experimental & molecular medicine)
[2020, 52(4):643-657]

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