Article
Oncology
Huijie Gao, Zhaobin He, Chao Gao, Naiqing Liu, Zhaoyang Zhang, Weibo Niu, Jun Niu, Cheng Peng
Summary: This study identified exosome-encapsulated miR-3124-5p as a promoter of the malignant progression of cholangiocarcinoma by targeting GDF11. Exosomal miR-3124-5p and GDF11 could potentially serve as biomarkers or therapeutic targets for cholangiocarcinoma.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Marta Correia de Sousa, Nicolas Calo, Cyril Sobolewski, Monika Gjorgjieva, Sophie Clement, Christine Maeder, Dobrochna Dolicka, Margot Fournier, Laurent Vinet, Xavier Montet, Jean-Francois Dufour, Bostjan Humar, Francesco Negro, Christine Sempoux, Michelangelo Foti
Summary: Despite being considered a potent oncomiR in human cancers, genetic deletion of miR-21 in mouse models surprisingly promotes hepatocellular carcinoma (HCC) development by affecting various signaling pathways and immune responses. These results challenge the current belief in miR-21 as an oncogene and raise caution regarding using miR-21 inhibition as a therapeutic approach for HCC.
Article
Gastroenterology & Hepatology
Pedro M. Rodrigues, Marta B. Afonso, Andre L. Simao, Tawhidul Islam, Maria M. Gaspar, Colm J. O'Rourke, Monika Lewinska, Jesper B. Andersen, Enara Arretxe, Cristina Alonso, Alvaro Santos-Laso, Laura Izquierdo-Sanchez, Raul Jimenez-Aguero, Emma Eizaguirre, Luis Bujanda, Maria J. Pareja, Carina Prip-Buus, Jesus M. Banales, Cecilia M. P. Rodrigues, Rui E. Castro
Summary: This study evaluated the role of hsa-miRNA-21-5p in the development of hepatocellular carcinoma (HCC) in non-alcoholic fatty liver disease (NAFLD) patients. The expression of hsa-miRNA-21-5p was found to increase with NAFLD severity and was associated with hepatic lipotoxicity. Inhibition of hsa-miRNA-21-5p was shown to prevent the progression of NAFLD to NASH and HCC.
LIVER INTERNATIONAL
(2023)
Article
Agriculture, Dairy & Animal Science
Kai-Zhi Zhou, Peng-Fei Wu, Xuan-Ze Ling, Jin Zhang, Qi-Fan Wang, Xin-Chao Zhang, Qian Xue, Tao Zhang, Wei Han, Gen-Xi Zhang
Summary: This study demonstrated that miR-460b-5p positively regulates the proliferation and differentiation of chicken myoblasts and that RBM19 is a target gene of miR-460b-5p. These findings are important for understanding the regulatory mechanism of meat development in broilers.
Article
Multidisciplinary Sciences
Won Jin Ho, Julianne N. P. Smith, Young Soo Park, Matthew Hadiono, Kelsey Christo, Alvin Jogasuria, Yongyou Zhang, Alyssia V. Broncano, Lakshmi Kasturi, Dawn M. Dawson, Stanton L. Gerson, Sanford D. Markowitz, Amar B. Desai
Summary: Emerging evidence suggests that prostaglandin E2 (PGE2), an eicosanoid molecule, plays an important role in promoting tissue regeneration in multiple organ systems after injury. As aging is characterized by a decline in the regenerative capacity of tissue stem cells, this study investigated the role of the prostaglandin-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in the diminished organ fitness of aged mice. The results showed that genetic loss of 15-PGDH conferred a protective effect on the aging of murine hematopoietic and gastrointestinal tissues. Aged mice lacking 15-PGDH showed increased hematopoietic output and accelerated recovery after transplantation compared to their wild-type counterparts. Additionally, loss of Hpgd expression resulted in improved gastrointestinal fitness and reduced inflammation in response to colitis. These findings suggest that 15-PGDH negatively regulates tissue regeneration in aging and that inhibiting 15-PGDH could be a potential therapeutic strategy to alleviate age-related loss of organ fitness.
Article
Oncology
Baiyin Zhong, Caixin Song, Qingfang He, Zhixi Chen, Qicheng Liao, Qiusheng Xiong, Shijie Wang, Yuansheng Xiao, Xing Xie, Yuankang Xie, Xiaonong Wang, Jianhong Zhang
Summary: This study reveals that LINC00630 is significantly upregulated in cholangiocarcinoma and promotes cell proliferation, migration, and invasion by upregulating FGF7 through miR-199a sponging.
Article
Pharmacology & Pharmacy
Alan B. Dogan, Nathan A. Rohner, Julianne N. P. Smith, Jessica A. Kilgore, Noelle S. Williams, Sanford D. Markowitz, Horst A. von Recum, Amar B. Desai
Summary: As the prevalence of age-related fibrotic diseases continues to rise, finding new antifibrotic therapies is crucial. This study lays the groundwork for a sustained release platform for a small-molecule inhibitor of the 15-hydroxyprostaglandin dehydrogenase (15-PGDH) enzyme. By using fine-tuned cyclodextrin microparticles, the delivery time of the inhibitor was extended to over one week.
Article
Oncology
Janson Tse, Thomas Pierce, Annalisa L. E. Carli, Mariah G. Alorro, Stefan Thiem, Eric G. Marcusson, Matthias Ernst, Michael Buchert
Summary: MicroRNA-21 (miR-21) is a small, non-coding RNA that is overexpressed in gastric cancer and other solid malignancies, with both pro- and anti-tumorigenic properties. However, the regulation of miR-21 and the effects of its inhibition in gastric cancer are not fully understood. In this study, the researchers investigated the molecular pathways that control miR-21 expression in gastric cancer and evaluated the therapeutic potential of targeting miR-21 with a synthetic miR-21 antagomir. They found that miR-21 expression in early gastric cancer is dependent on Stat3, which is activated by IL-6 family cytokines through the gp130 receptor. Inhibition of miR-21 with the antagomir reduced gastric tumor growth, epithelial-to-mesenchymal transition, and matrix remodeling. The study highlights miR-21 as a promising target for anti-cancer therapy in gastric cancer.
Article
Cell Biology
Jianfei Tu, Weiqian Chen, Liyun Zheng, Shiji Fang, Dengke Zhang, Chunli Kong, Yang Yang, Rongfang Qiu, Zhongwei Zhao, Chenying Lu, Xiaojie Lu, Jiansong Ji
Summary: The study revealed that circ_0021205 was up-regulated in CCA and positively correlated with tumor size and TNM stage. It promoted the proliferation, migration, and invasion of CCA cells by sponging miR-204-5p and regulating the expression of RAB22A, serving as a potential diagnostic biomarker or therapeutic target for CCA.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Chemistry, Medicinal
Bin Hu, Kosuke Toda, Xiaoyu Wang, Monika I. Antczak, Julianne Smith, Sophie Geboers, Gen Nishikawa, Hongyun Li, Dawn Dawson, Stephen Fink, Amar B. Desai, Noelle S. Williams, Sanford D. Markowitz, Joseph M. Ready
Summary: In this study, a novel class of quinoxaline amides was found to exhibit potent inhibition of 15-PGDH, resulting in elevated levels of PGE2 and promoting tissue repair and regeneration. These compounds also demonstrated good oral bioavailability and protective activity in mouse models of ulcerative colitis and recovery from bone marrow transplantation.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Giulia Romano, Patricia Le, Giovanni Nigita, Michela Saviana, Lavender Micalo, Francesca Lovat, Daniel del Valle Morales, Howard Li, Patrick Nana-Sinkam, Mario Acunzo
Summary: Non-small cell lung cancer (NSCLC) patients with an epidermal growth factor receptor (EGFR) mutation show a positive initial response to tyrosine kinase inhibitors (TKIs), but rapid resistance is often developed due to genetic alterations, including amplification of hepatocyte growth factor receptor (MET) and its abnormal activity. The role of RNA post-transcriptional modifications, specifically adenosine-to-inosine (A-to-I) RNA editing, in the aberrant expression of MET in cancer, particularly NSCLC, is not well-studied. In this study, the researchers investigated the effect of edited miR-411-5p on NSCLC cell lines and found that it directly targets MET and negatively affects the mitogen-activated protein kinases (MAPKs) pathway. By overexpressing edited miR-411-5p, the researchers observed reduced proliferation and increased apoptosis in TKI-resistant NSCLC cells, indicating a potential improvement in EGFR TKI response.
Article
Biotechnology & Applied Microbiology
Hao Jia, Wei Sun, Xiangbo Li, Wenhao Xu
Summary: MEL has been found to effectively inhibit the growth of thyroid cancer and suppress tumor cell proliferation while promoting apoptosis. MEL also regulates the expression of certain genes and proteins to further promote tumor cell apoptosis.
Article
Biology
Arianna Pocaterra, Gloria Scattolin, Patrizia Romani, Cindy Ament, Silvia Ribback, Xin Chen, Matthias Evert, Diego F. Calvisi, Sirio Dupont
Summary: The study demonstrates that Fascin1 plays a key role in sustaining YAP activation in response to mechanical cues in the tumor environment, highlighting its potential as a clinical target for intrahepatic cholangiocarcinoma. Mechanically forces influence cancer progression by activating YAP through actomyosin. This finding suggests Fascin1 as a pro-oncogenic mechanism that could be targeted for therapeutic interventions in liver cancer.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Prema L. Mallipeddi, Yongyou Zhang, Hongyun Li, Sanford D. Markowitz, Bruce Posner
Summary: SW033291 is a compound discovered in a high throughput chemical screen as an inhibitor of 15-prostaglandin dehydrogenase (15-PGDH), showing potential in promoting tissue regeneration in in vivo mouse models. Docking and molecular dynamics simulations reveal key binding interactions of SW033291 with specific residues in 15-PGDH, leading to enantioselectivity for the R-enantiomer. Comparisons with other 15-PGDH inhibitors shed light on the unique binding mode of (R)-S(O)-SW033291.
Review
Gastroenterology & Hepatology
Colm J. O'Rourke, Patricia Munoz-Garrido, Jesper B. Andersen
Summary: Cholangiocarcinoma (CCA) is a rare disease without diagnostic biomarkers, making population screening infeasible. Most CCA patients require systemic clinical management, and this review discusses the therapeutic potential of molecular targets at different stages of development, as well as the successes and failures of CCA-targeted therapies and the lessons learned.
