Review
Genetics & Heredity
Jun Liu, Madeline A. Sauer, Shaza G. Hussein, Junyu Yang, Daniel G. Tenen, Li Chai
Summary: SALL4, a transcription factor important in embryonic stem cells, is re-expressed in various human cancers and its dysregulation contributes to cancer pathogenesis and drug resistance. Recent studies suggest that miRNAs play a crucial role in controlling SALL4 expression, making them promising therapeutic targets for cancer treatment.
Article
Biochemistry & Molecular Biology
Hailin Zou, Juan Luo, Yibo Guo, Yuhong Liu, Yun Wang, Liang Deng, Peng Li
Summary: This study reveals that the RNA binding protein LIN28 plays a role in modulating the cancer stem cell-like properties and tumor progression in triple negative breast cancer (TNBC) through the Hippo signaling pathway. LIN28 overexpression is correlated with poorer overall survival in TNBC patients. The study also highlights the LIN28/MSI2-YAP1 regulatory axis as a potential therapeutic strategy for TNBC with LIN28 overexpression.
Article
Biochemistry & Molecular Biology
Calder W. Reinsborough, Helene Ipas, Nathan S. Abell, Ellen B. Gouws, J. Paige Williams, Marvin Mercado, Carla Van den Berg, Blerta Xhemalce
Summary: BCDIN3D plays a crucial role in regulating metabolic pathways in cancer, with a connection to increased glycolysis and reduced glucose metabolism capacity, while also regulating ALDOC expression. This connection may be relevant to breast cancer, obesity, and T2D.
Article
Ophthalmology
Lorena Teixeira Frasson, Barbara Dalmaso, Priscilla Sayami Akamine, Edna Teruko Kimura, Dania Emi Hamassaki, Carolina Beltrame Del Debbio
Summary: The study reveals that Let-7 miRNA is expressed at higher rates in adult CE cells, while Lin28 and Hmga2 are more expressed in newborns. Neurospheres show higher expression of Lin28 and Hmga2 compared to newborn and adult cells.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Dae-Won Lee, Sungho Shin, Jeong-Ho Kim, Cheolju Lee, In Yong Kim, Il-Hoan Oh
Summary: The inhibition of let-7 miRNAs enhances the therapeutic potential of MSCs by promoting cell proliferation, migration, and regenerative processes. It does not alter the fate of MSCs but instead induces functional changes accompanied by changes in proteomics. In addition, let-7-inhibited MSCs promote self-renewal of hematopoietic progenitor cells and enhance capillary formation in endothelial cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Seong Heon Kim, Bi-Oh Park, Kidae Kim, Byoung Chul Park, Sung Goo Park, Jeong-Hoon Kim, Sunhong Kim
Summary: This study revealed that Sjogren Syndrome antigen B (SSB) protein interacts with LIN28A and LIN28B in the nucleus, regulating the LIN28-let-7 axis and impacting developmental timing control.
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
(2021)
Article
Chemistry, Medicinal
Georg L. L. Goebel, Lisa Hohnen, Lydia Borgelt, Pascal Hommen, Xiaqiu Qiu, Helen Lightfoot, Peng Wu
Summary: The study reports the inhibitory activities of a series of small molecules with tricyclic tetrahydroquinoline structure against LIN28. It identifies the structural features required for LIN28 inhibition and emphasizes the importance of developing small molecules with new scaffolds as LIN28-targeting probes and therapeutic candidates.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Zeyu Shi, Sally K. Y. To, Shuaishuai Zhang, Shan Deng, Margarita Artemenko, Minda Zhang, Juan Tang, Jin-Zhang Zeng, Alice S. T. Wong
Summary: Nur77 functions as a novel regulator of microRNA biogenesis in promoting CRC progression under hypoxia, potentially through inhibition of p63-dependent transcription. Knockdown of Nur77 or overexpression of let-7i-5p can inhibit CRC metastasis.
Article
Biology
Qiuying Liu, Xiaoli Chen, Mariah K. Novak, Shaojie Zhang, Wenqian Hu
Summary: Research shows that Trim71 represses Ago2 mRNA translation in mouse embryonic stem cells, which leads to an increase in mature let-7 microRNAs and affects stemness and differentiation. This highlights the importance of repressing the prodifferentiation let-7 microRNAs for maintaining pluripotency.
Review
Biochemistry & Molecular Biology
Chien-Hsiu Li, Chiao-Chun Liao
Summary: Cancer is often the result of abnormal glucose uptake and imbalanced nutrient metabolism. Dysregulation of glucose metabolism and autophagy, as well as the involvement of miRNA Let-7, play crucial roles in tumor progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Qian Zhang, Mengyun Shi, Ruiling Zheng, Haoyi Han, Xin Zhang, Feng Lin
Summary: This study demonstrates that C1632 can inhibit the proliferation and migration of ovarian cancer cells by concurrently inhibiting the LIN28B/let-7/FAK signaling pathway and FAK phosphorylation, and it also exhibits a significant inhibitory effect on ovarian cancer xenograft tumors in mice. Therefore, C1632 is a promising onco-therapeutic agent for the treatment of ovarian cancer.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Review
Cell Biology
Yuxi Ma, Na Shen, Max S. Wicha, Ming Luo
Summary: Cancer stem-like cells play a critical role in tumorigenesis, cancer progression, treatment resistance, and metastatic relapse. The let-7 family of microRNAs is important in regulating cancer stemness through various RNA-binding proteins, long non-coding RNAs, and circular RNAs. Targeting let-7 for cancer therapeutics has the potential to improve treatment efficacy by specifically targeting CSCs and modulating metabolic pathways.
Article
Chemistry, Medicinal
Lydia Borgelt, Fu Li, Pascal Hommen, Philipp Lampe, Jimin Hwang, Georg L. Goebel, Sonja Sievers, Peng Wu
Summary: Studies have identified trisubstituted pyrrolinones as small-molecule inhibitors disrupting the interaction between LIN28 and let-7, with the most potent compound C902 showing dose-dependent inhibition. The structure-activity relationship study revealed important structural features contributing to either PRI inhibition or PPI stabilization. These pyrrolinones represent a new class of LIN28-binding molecules and the first examples of small molecules that showed substituent-dependent PRI inhibitory and PPI activating activities.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Lydia Borgelt, Fubao Huang, Lisa Hohnen, Xiaqiu Qiu, Georg L. L. Goebel, Pascal Hommen, Peng Wu
Summary: A new LIN28 inhibitor has been discovered, which disrupts the interaction between LIN28 and let-7 miRNA, inhibiting LIN28 expression and cancer cell proliferation. This finding provides a potential candidate for the development of next-generation LIN28 inhibitors.
Article
Physiology
Ying Huang, Manshu Yu, Akihiro Kuma, Janet D. Klein, Yanhua Wang, Faten Hassounah, Hui Cai, Xiaonan H. Wang
Summary: This study found that Acu/LFES enhances protein synthesis in both hindlimb and forelimb muscles by reducing let-7-5p levels, which leads to upregulation of the Igf1 signaling pathway. This provides a new understanding of how electrical acupuncture treatment positively influences muscle health.
FRONTIERS IN PHYSIOLOGY
(2021)
Review
Clinical Neurology
Daisuke Ito, Satoru Morimoto, Shinichi Takahashi, Kensuke Okada, Jin Nakahara, Hideyuki Okano
Summary: Significant progress has been made in drug screening for amyotrophic lateral sclerosis using patient-derived induced pluripotent stem cells, leading to the identification of candidate drugs and the advancement of clinical trials. This stem cell-based approach shows safety and positive effects, reducing costs and time compared to animal testing.
Article
Biotechnology & Applied Microbiology
Ryota Tamura, Hiroyuki Miyoshi, Kent Imaizumi, Masahiro Yo, Yoshitaka Kase, Tsukika Sato, Mizuto Sato, Yukina Morimoto, Oltea Sampetrean, Jun Kohyama, Munehisa Shinozaki, Atsushi Miyawaki, Kazunari Yoshida, Hideyuki Saya, Hideyuki Okano, Masahiro Toda
Summary: This study demonstrates the potential benefit of gene-edited induced pluripotent stem cells (iPSCs) for the treatment of invasive glioma stem cells (GSCs). Neural stem cells (NSCs) derived from CRISPR/Cas9-edited iPSCs expressing a suicide gene showed enhanced tumor-trophic migratory capacity and significant in vivo antitumor effects. The study also identified key signaling pathways and gene expressions associated with the efficacy of therapeutic iPSC-NSCs.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2023)
Article
Cell Biology
Satoru Morimoto, Koichi Saeki, Masaru Takeshita, Kunio Hirano, Mariko Shirakawa, Yumiko Yamada, Shiho Nakamura, Fumiko Ozawa, Hideyuki Okano
Summary: The study developed an intranasal vaccine for COVID-19 by using a Sendai virus vector loaded with the receptor binding domain of SARS-CoV-2 as an antigen. The vaccine induced a strong immune response, with increased levels of S-RBD-specific antibodies in serum and bronchoalveolar lavage fluid. The booster dose further enhanced the production of neutralizing antibodies, indicating the effectiveness of the vaccine.
Article
Cell Biology
Sho Yoshimatsu, Mayutaka Nakajima, Iki Sonn, Rie Natsume, Kenji Sakimura, Ena Nakatsukasa, Toshikuni Sasaoka, Mari Nakamura, Takashi Serizawa, Tsukika Sato, Erika Sasaki, Hongkui Deng, Hideyuki Okano
Summary: This study compared the gene expression profiles of mouse, human, and common marmoset EPSCs using transcriptomic approaches. The marmoset EPSC-like cells displayed a distinct morphology but exhibited a pluripotent state similar to embryonic stem cells. They also showed interspecies chimeric contribution to mouse embryos. Furthermore, the gene expression of the marmoset EPSC-like cells resembled that of human EPSCs. Overall, this study evaluated the efficacy of the method for deriving marmoset EPSCs.
Article
Cell & Tissue Engineering
Yuji Okano, Yoshitaka Kase, Hideyuki Okano
Summary: The emergence of single-cell RNA sequencing has revolutionized the study of cellular diversity. Conventional methods for annotating RNA-seq data have limitations in capturing universal characteristics of a cell type. This study presents a new framework for managing cellular identities based on set theory, allowing for comparisons across datasets while preserving biological semantics.
Article
Biochemistry & Molecular Biology
Tosho Kondo, Ihori Ebinuma, Hirotaka Tanaka, Yukitoshi Nishikawa, Takaki Komiya, Mitsuru Ishikawa, Hideyuki Okano
Summary: In this study, an effective high-throughput screening system was established using induced pluripotent stem cells (iPSCs) to generate motor neurons. The generated motor neurons exhibited characteristics similar to ALS neurons and showed abnormal protein accumulation and hyperexcitability. Treatment with rapamycin and retigabine normalized activity and improved neuronal survival. This study provides a valuable platform for discovering novel ALS therapeutics and personalized medicine approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell & Tissue Engineering
Shota Okura, Honoka Ishii, Ayano Suzuki, Chika Saegusa, Ko Fujiki, Kenshi Sugano, Noriomi Suzuki, Tsubasa Saeki, Saeko Matsuzaki, Hiroyuki Ozawa, Masato Fujioka, Makoto Hosoya, Hideyuki Okano
Summary: We have established two human-induced pluripotent stem cell (iPSC) lines from individuals without auditory disorders and confirmed normal hearing through extensive audiometry tests. These iPSC lines express pluripotency genes and are capable of differentiating into the three germ layers. They will be used as controls for pathological analysis and drug screening for ear disorders.
STEM CELL RESEARCH
(2023)
Article
Cell & Tissue Engineering
Ryotaro Imai, Ryota Tamura, Masahiro Yo, Mizuto Sato, Mariko Fukumura, Kento Takahara, Yoshitaka Kase, Hideyuki Okano, Masahiro Toda
Summary: Despite limited treatment options for traumatic brain injury (TBI), neural stem/progenitor cells (NS/PCs) derived from induced pluripotent stem cells (iPSCs) expressing yCD-UPRT showed promising results in functional recovery. The transplanted iPSC-derived NS/PCs displayed stable expression of the therapeutic gene and concentrated around the damaged cortex, leading to improved behavioral performance and prevention of secondary brain injury in a TBI mouse model. In addition, selective elimination of undifferentiated NS/PCs using 5-fluorocytosine (5-FC) demonstrated the safety of this regenerative medicine approach.
Article
Biology
Miho Isoda, Tsukasa Sanosaka, Ryo Tomooka, Yo Mabuchi, Munehisa Shinozaki, Tomoko Andoh-Noda, Satoe Banno, Noriko Mizota, Ryo Yamaguchi, Hideyuki Okano, Jun Kohyama
Summary: A single-cell approach identified cellular properties of neural and mesenchymal origins in human induced pluripotent stem cells, shedding light on the causes of undesired grafts after transplantation.
COMMUNICATIONS BIOLOGY
(2023)
Article
Immunology
Emi Qian, Masahiro Uemura, Hiroya Kobayashi, Shiho Nakamura, Fumiko Ozawa, Sho Yoshimatsu, Mitsuru Ishikawa, Osamu Onodera, Satoru Morimoto, Hideyuki Okano
Summary: CARASIL is a inherited small vessel disease caused by mutations in the HTRA1 gene. Heterozygous mutations in HTRA1 have been found to cause clinical features of the disease. Researchers have successfully established a hiPSC line from a patient with heterozygous HTRA1-related CSVD, which has normal morphology and karyotype. The hiPSCs expressed pluripotency-related markers and had the ability to differentiate into all three germ layers in vitro, providing a valuable tool for studying the cellular mechanisms of HTRA1 mutation.
INFLAMMATION AND REGENERATION
(2023)
Article
Biochemistry & Molecular Biology
Hitomi Ono-Minagi, Tsutomu Nohno, Takashi Serizawa, Yu Usami, Takayoshi Sakai, Hideyuki Okano, Hideyo Ohuchi
Summary: This study investigates the embryonic origin of salivary and lacrimal glands using transgenic mice and demonstrates that these glands contain cells derived from all three germ layers. Specifically, a subset of cells derived from neural crest differentiate into epithelial cells and express high levels of stem cell markers. These cells play an important role in the regenerative response following tissue damage.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Hiroya Kobayashi, Koji Ueda, Satoru Morimoto, Mitsuru Ishikawa, Nicolas Leventoux, Ryogen Sasaki, Yoshifumi Hirokawa, Yasumasa Kokubo, Hideyuki Okano
Summary: The proteins in extracellular vesicles derived from astrocytes in patients with Kii ALS/PDC exhibit distinctive patterns compared to healthy individuals, with increased proteins related to proteostasis and decreased proteins related to anti-inflammation.
NEUROLOGICAL SCIENCES
(2023)
Review
Medicine, General & Internal
Takahiro Shibata, Syoichi Tashiro, Masaya Nakamura, Hideyuki Okano, Narihito Nagoshi
Summary: Cell transplantation therapy using human-induced pluripotent stem cell-derived neural stem/progenitor cells has shown efficacy in treating the subacute phase of spinal cord injury. However, there is a lack of focus on treatment in the chronic phase, which poses challenges in overcoming factors specific to chronic SCI. Combining different therapies and addressing issues in severe injury models and functional recovery are important for regenerative therapy in chronic SCI.
MEDICINA-LITHUANIA
(2023)
Article
Geriatrics & Gerontology
Shohei Komaki, Masatoshi Nagata, Eri Arai, Ryo Otomo, Kanako Ono, Yukiko Abe, Hideki Ohmomo, So Umekage, Natsuko Shinozaki, Tsuyoshi Hachiya, Yoichi Sutoh, Yayoi Otsuka-Yamasaki, Yasumichi Arai, Nobuyoshi Hirose, Akio Yoneyama, Hideyuki Okano, Makoto Sasaki, Yae Kanai, Atsushi Shimizu
Summary: This study explored the epigenetic signatures of exceptional healthy longevity and found that it depends not only on maintaining young epigenetic states but also on advanced states of specific epigenetic regions.
LANCET HEALTHY LONGEVITY
(2023)
Review
Biochemistry & Molecular Biology
Hideyuki Okano, Satoru Morimoto, Chris Kato, Jin Nakahara, Shinichi Takahashi
Summary: In recent years, clinical trials using iPSC technology for disease modeling and drug discovery have shown promising results, particularly for the treatment of ALS. ROPi has been identified as a potential ALS treatment and has undergone clinical trials and reverse translational research, demonstrating its ability to delay disease progression and prolong survival in ALS patients.
JOURNAL OF NEUROCHEMISTRY
(2023)