Article
Biochemistry & Molecular Biology
Sylwia Chocholska, Michal Zarobkiewicz, Agata Szymanska, Natalia Lehman, Justyna Wos, Agnieszka Bojarska-Junak
Summary: The aim of this study was to investigate the expression of miR-17 similar to 92 cluster members in CLL patients. The study provides new evidence regarding the heterogeneity of miR-17 similar to 92 cluster members' expression in CLL patients. High miR-20a expression can be considered an independent favorable prognostic factor.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Kexin Li, Jiongyu Chen, Xiaoying Lou, Yiling Li, Benheng Qian, Danfei Xu, Yue Wu, Shaohui Ma, Donghong Zhang, Wei Cui
Summary: The study revealed that the dynamic changes in 25 m6A regulators were associated with the clinical features and prognosis of patients with esophageal cancer, with HNRNPA2B1 possibly affecting the prognosis of esophageal cancer patients by regulating the miR-17-92 cluster.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Myung Chan Park, Hyoji Kim, Hoyun Choi, Mee Soo Chang, Suk Kyeong Lee
Summary: The EBV-associated miRNA miR-BART1-3p plays a role in cell cycle regulation and cell growth by targeting E2F3. Moreover, miR-BART1-3p may also affect the expression of the miR-17-92 cluster by downregulating E2F3.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Fabrizio Favaloro, Annina M. DeLeo, Ana C. Delgado, Fiona Doetsch
Summary: Neural stem cells in the adult ventricular-subventricular zone play a crucial role in generating neurons and glia. MicroRNAs, specifically miR-17 and miR-92, are found to be highly upregulated in the activated stem cells and transit amplifying cells. Their deletion has stage-specific effects, affecting proliferation and differentiation of various subpopulations within the adult ventricular-subventricular zone. These findings highlight the importance of miR-17 and miR-92 in regulating neural stem cell function.
Article
Medicine, Research & Experimental
Yan Sweat, Ryan J. Ries, Mason Sweat, Dan Su, Fan Shao, Steven Eliason, Brad A. Amendt
Summary: Anaplastic thyroid cancer is a highly metastatic cancer expressing high levels of the miR-17-92 cluster. Inhibition of miR-17 unexpectedly promotes the expression of other oncogenic miRs within the cluster, leading to cancer progression. The study suggests a complex regulatory role of miR-17 in thyroid tumor growth.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2021)
Article
Biochemistry & Molecular Biology
Madara Ratnadiwakara, Mohamed N. M. Bahrudeen, Erika Aikio, Piia Takabe, Rebekah M. Engel, Zileena Zahir, Thierry Jarde, Paul J. McMurrick, Helen E. Abud, Minna-Liisa Anko
Summary: This study reveals that Serine-arginine rich splicing factor 3 (SRSF3) plays a crucial role in the processing of miR-17-92 cluster miRNAs in pluripotent and cancer cells. SRSF3 binding to CNNC motifs downstream of Drosha cleavage sites is required for efficient processing of the cluster. The interaction between SRSF3 and miR-17-92 results in changes in RNA structure and an increase in miR-17 and miR-20a levels, promoting self-renewal and contributing to colorectal cancer pathogenesis.
Article
Biochemistry & Molecular Biology
Clara Boces-Pascual, Aida Mata-Ventosa, Mireia Martin-Satue, Loreto Boix, Meritxell Gironella, Marcal Pastor-Anglada, Sandra Perez-Torras
Summary: Downregulation of hCNT1 protein was found in both colorectal and pancreatic ductal adenocarcinoma, potentially regulated by miR-106a and miR-17, leading to chemoresistance to fluoropyrimidine-based treatments.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Genetics & Heredity
Fang Lu, Xianghong Zhao, Zhongqiu Zhang, Mengqiu Xiong, Ying Wang, Yalan Sun, Bangshun He, Junrong Zhu
Summary: This meta-analysis suggests that the miR-17-92 cluster may serve as a diagnostic and prognostic biomarker for hepatocellular carcinoma (HCC), but further large-scale, multicenter, and high-quality studies are needed for validation.
FRONTIERS IN GENETICS
(2022)
Article
Oncology
Yuka Kawaji-Kanayama, Taku Tsukamoto, Masakazu Nakano, Yuichi Tokuda, Hiroaki Nagata, Kentaro Mizuhara, Yoko Katsuragawa-Taminishi, Reiko Isa, Takahiro Fujino, Yayoi Matsumura-Kimoto, Shinsuke Mizutani, Yuji Shimura, Masafumi Taniwaki, Kei Tashiro, Junya Kuroda
Summary: The miR-17-92 cluster activates the BCR signaling pathway in MCL by regulating BTG2, resulting in cell proliferation. Silencing BTG2 leads to overactivation of the BCR signaling pathway and cell proliferation. These findings contribute to predicting therapeutic efficacy and improving outcomes in MCL.
Review
Genetics & Heredity
Xuefeng Pan, Xiao Cen, Xiner Xiong, Zhihe Zhao, Xinqi Huang
Summary: Osteoarthritis is a common joint disease, especially in the elderly population. It leads to joint pain and disability, reducing patients' quality of life and increasing social burden. The pathophysiology of osteoarthritis is characterized by cartilage hypertrophy or defect, subchondral bone sclerosis, and synovitis. Research suggests that certain miRNAs are closely related to the pathological processes of osteoarthritis, providing new avenues for diagnosis and treatment.
FRONTIERS IN GENETICS
(2022)
Article
Cell Biology
Yelei Cen, Jinjin Qi, Liang Chen, Caixia Xia, Min Zheng, Yanning Liu, Guohua Lou
Summary: This study revealed that aging and replicative cellular senescence reduce the therapeutic potential of mesenchymal stem cells (MSCs) on acute liver failure (ALF). The expression of miR-17-92 cluster members, especially miR-17 and miR-20a, was found to be decreased in senescent MSCs and was associated with decreased levels of the oncogene c-Myc during MSC senescence. Modifying the expression of these key miRNAs reversed senescence features of MSCs and improved their therapeutic effect on ALF.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Endocrinology & Metabolism
Hongqi Xin, Zhongwu Liu, Benjamin Buller, Yanfeng Li, William Golembieski, Xinling Gan, Fengjie Wang, Mei Lu, Meser M. Ali, Zheng G. Zhang, Michael Chopp
Summary: Exosomes enriched with the MiR-17-92 cluster derived from multipotent mesenchymal stromal cells (MSCs) can enhance functional recovery after transient stroke, potentially by promoting axonal extension and myelination. This enhancement in axon-myelin remodeling may be mediated through the activation of the PI3K/Akt/mTOR pathway induced by downregulation of PTEN.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2021)
Article
Oncology
Yi Shen, Yi Shao, Xiaoli Ruan, Lingyan Zhu, Zhaoping Zang, Tong Wei, Rena Nakyeyune, Wenqiang Wei, Fen Liu
Summary: This study found that the rs1804506 polymorphism located in miR-17-92 cluster binding sites is associated with the susceptibility of ESCC, especially in older individuals, females, or non-smokers. The rs1804506 T allele reduces the binding of miR-19a-3p and TGFBR3, suggesting its potential role in ESCC development.
Article
Cell Biology
Jun Xie, Ying Du, Dewang Liu, Jianfeng Wu, Kang Yang, Xiaoyu He, Jiayi Zhao, Peicheng Hong, Kunyu Liao, Huanrong Zhang, Yazhen Hong, John R. Teijaro, Seung Goo Kang, Changchun Xiao, Wen-Hsien Liu
Summary: The miR-17 similar to 92 family microRNAs play a key role in T cell and plasma cell differentiation. In this study, researchers found that the miR-17 similar to 92 family also has important functions in B cell differentiation and function, regulating the key target gene Socs3 in plasma cell differentiation.
Article
Oncology
Vishaka Gopalan, Arashdeep Singh, Farid Rashidi Mehrabadi, Li Wang, Eytan Ruppin, H. Efsun Arda, Sridhar Hannenhalli
Summary: This study identifies edge epithelial cell states with oncogenic transcriptional activity in human organs without oncogenic mutations, with a particular focus on pancreatic ductal adenocarcinoma (PDAC). It also highlights the increase in the fraction of acinar cells with age in the pancreas, as well as the significantly higher presence of AE-like cells in human pancreatitis samples.
Article
Gastroenterology & Hepatology
Marta Alonso-Nocelo, Laura Ruiz-Canas, Patricia Sancho, Kivanc Gorgulu, Sonia Alcala, Coral Pedrero, Mireia Vallespinos, Juan Carlos Lopez-Gil, Marina Ochando, Elena Garcia-Garcia, Sara Maria David Trabulo, Paola Martinelli, Patricia Sanchez-Tomero, Carmen Sanchez-Palomo, Patricia Gonzalez-Santamaria, Lourdes Yuste, Sonja Maria Wormann, Derya Kabacaoglu, Julie Earl, Alberto Martin, Fernando Salvador, Sandra Valle, Laura Martin-Hijano, Alfredo Carrato, Mert Erkan, Laura Garcia-Bermejo, Patrick C. Hermann, Hana Algul, Gema Moreno-Bueno, Christopher Heeschen, Francisco Portillo, Amparo Cano, Bruno Sainz
Summary: LOXL2 plays an important role in pancreatic ductal adenocarcinoma (PDAC), with its loss inhibiting metastasis and prolonging overall survival, while overexpression promotes tumor growth and decreases overall survival. Macrophage-secreted OSM is an inducer of LOXL2 expression, with targeting macrophages affecting its expression and collagen fiber alignment.
Article
Medicine, Research & Experimental
Beatriz Parejo-Alonso, Alba Royo-Garcia, Pilar Espiau-Romera, Sarah Courtois, Alvaro Curiel-Garcia, Sladjana Zagorac, Isabel Villaoslada, Kenneth P. Olive, Christopher Heeschen, Patricia Sancho
Summary: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by metastasis and chemoresistance. Targeting the ALK signaling pathway can decrease tumor formation and chemoresistance in PDAC by inhibiting pancreatic cancer stem cells.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Immunology
Alberto Benito-Martin, Laura Nogues, Marta Hergueta-Redondo, Elena Castellano-Sanz, Eduardo Garvin, Michele Cioffi, Paloma Sola-Castrillo, Weston Buehring, Pilar Ximenez-Embun, Javier Munoz, Irina Matei, Josep Villanueva, Hector Peinado
Summary: Metastatic disease is a leading cause of cancer-related deaths. Mast cells, a type of immune cells, play a crucial role in the formation of pre-metastatic niche. Surprisingly, mast cells have both pro-metastatic and anti-metastatic effects, as shown in in vivo and in vitro studies. The expression and secretion of HMGA1 in melanoma cells are associated with metastatic behavior, and targeting HMGA1 can reduce melanoma metastasis. These findings provide insights into the potential use of HMGA1 as a therapeutic target in melanoma.
Article
Oncology
Maren Stark, Marina Nicolai, Marina Tatura, Corinna U. Keber, Andreas Kaufmann, Ho-Ryun Chung, Emily P. Slater, Christopher Heeschen, Rita T. Lawlor, Aldo Scarpa, Detlef K. Bartsch, Thomas M. Gress, Stefan Bauer, Malte Buchholz
Summary: TLR7 is overexpressed in PDAC and is associated with shorter patient survival. Inhibition of TLR7 reduces cell viability in PDAC cell lines. However, global TLR7 deficiency does not affect survival or overall histopathological tumor features in PDAC mouse models.
Review
Biochemistry & Molecular Biology
Yaru Zhao, Jiajia Tang, Ke Jiang, Shin-Yi Liu, Alexandra Aicher, Christopher Heeschen
Summary: Pancreatic cancer is a deadly disease with increasing incidence and late-stage presentation, resulting in low survival rates. The lack of specific symptoms, biomarkers, and screening tools hinders early diagnosis. Liquid biopsies have emerged as a non-invasive and repeatable method for sampling and analyzing circulating tumor cells, small extracellular vesicles, and tumor DNA. Although liquid biopsies have the potential to aid in early detection, risk stratification, and precision medicine in pancreatic cancer, they have not yet become a routine tool for clinicians. This article summarizes recent findings on the use of liquid biopsy in pancreatic cancer patients, discussing current challenges and future perspectives on this potentially powerful alternative to conventional tissue biopsies.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2023)
Article
Oncology
Jonas Althaus, Verena Nilius-Eliliwi, Abdelouahid Maghnouj, Sascha Doering, Roland Schroers, Michael Hudecek, Stephan A. Hahn, Thomas Mika
Summary: Chimeric antigen receptors (CARs) have been effective in improving cancer immunotherapy, especially using immune cells like NK cells or T cells as effector cells. NK92 cells, a cell line with known cytotoxic activity, are particularly promising in CAR therapy due to their simplicity in culturing conditions and proven anti-tumor efficacy with a manageable safety profile. Understanding the cytotoxic mechanisms of CAR effector cells is crucial in uncovering potential resistance mechanisms, especially in lymphoma cases with frequent apoptosis pathway mutations. This study found that the perforin/granzyme pathway is the major pathway mediating cytotoxicity in CD19-CAR-NK92 cells, as knockout of perforin 1 significantly reduced their cytotoxicity.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Review
Oncology
Qi Wang, Berina Sabanovic, Azhar Awada, Chiara Reina, Alexandra Aicher, Jiajia Tang, Christopher Heeschen
Summary: Pancreatic cancer is a deadly disease with limited treatment options due to late diagnosis. Liquid biopsies, particularly circulating tumor cells (CTCs) and their single-cell omics analysis, have the potential to detect pancreatic cancer early and provide valuable molecular insights. CTCs offer comprehensive genomic, transcriptomic, epigenetic, and proteomic information that can help understand tumor heterogeneity and track cancer features. The emerging technology of ex vivo culturing of CTCs could enable the study of individual cancers and the development of personalized treatment approaches.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Gastroenterology & Hepatology
Feda H. Hamdan, Amro M. Abdelrahman, Ana Patricia Kutschat, Xin Wang, Thomas L. Ekstrom, Nidhi Jalan-Sakrikar, Catherine Wegner Wippel, Negar Taheri, Liezel Tamon, Waltraut Kopp, Joana Aggrey-Fynn, Aditya Bhagwate, Roberto Alva-Ruiz, Isaac Lynch, Jennifer Yonkus, Robyn Laura Kosinsky, Jochen Gaedcke, Stephan A. Hahn, Jens T. Siveke, Rondell Graham, Zeynab Najafova, Elisabeth Hessmann, Mark J. Truty, Steven A. Johnsen
Summary: This study discovered a group of enhancers called iHUBs, which are involved in transcriptional reprogramming and chemoresistance in pancreatic ductal adenocarcinoma (PDAC). Inhibiting or deleting iHUBs can decrease the transcription of target genes and sensitize resistant cells to chemotherapy. Targeting eRNA production or signaling pathways upstream of iHUB activation can restore chemotherapy responsiveness in vitro and in vivo.
Article
Oncology
Xin Wang, Ana P. Kutschat, Joana Aggrey-Fynn, Feda H. Hamdan, Rondell P. Graham, Alexander Q. Wixom, Yara Souto, Swetlana Ladigan-Badura, Jennifer A. Yonkus, Amro M. Abdelrahman, Roberto Alva-Ruiz, Jochen Gaedcke, Philipp Stroebel, Robyn Laura Kosinsky, Florian Wegwitz, Patrick Hermann, Mark J. Truty, Jens T. Siveke, Stephan A. Hahn, Elisabeth Hessmann, Steven A. Johnsen, Zeynab Najafova
Summary: The lack of molecular stratification approaches and targeted therapy is a major hurdle in applying precision oncology to pancreatic cancer. This study aimed to identify molecular and epigenetic signatures of a specific subclass of pancreatic ductal adenocarcinoma (PDAC) and validate their application for patient stratification and therapy monitoring. By analyzing gene expression and epigenome mapping data, the researchers identified subtype-specific enhancer regions and successfully confirmed the validity of enhancer RNA (eRNA) detection as a histologic approach for patient stratification. This study provides proof-of-concept that single-cell level detection of subtype-specific epigenetic changes is possible in complex primary tumor material.
MOLECULAR CANCER RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Rebeca Carrion-Marchante, Celia Pinto-Diez, Jose Ignacio Klett-Mingo, Esther Palacios, Miriam Barragan-Usero, M. Isabel Perez-Morgado, Manuel Pascual-Mellado, Sonia Alcala, Laura Ruiz-Canas, Bruno Sainz Jr, Victor M. Gonzalez, M. Elena Martin
Summary: Lung cancer is a major cause of cancer-related death worldwide. A previously identified aptamer, apMNKQ2, showed promising results as an antitumor drug in breast cancer. This study investigates the antitumor potential of apMNKQ2 in non-small cell lung cancer where MNK1 plays a significant role.
Article
Cell Biology
Britta Majchrzak-Stiller, Marie Buchholz, Ilka Peters, Daniel Waschestjuk, Johanna Strotmann, Philipp Hoehn, Stephan Hahn, Chris Braumann, Waldemar Uhl, Thomas Mueller, Hanns Moehler
Summary: GP-2250, a novel anticancer agent, inhibits energy metabolism by targeting hexokinase 2 and glyceraldehyde-3-phosphate dehydrogenase, resulting in a decrease in ATP level. It causes cytotoxicity primarily through a deficit in the tricarboxylic acid cycle, leading to impaired synthesis of fatty acids and proteins. In addition, GP-2250 disrupts NF-κB signaling, reducing tumour cell proliferation and promoting apoptosis.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2023)
Article
Oncology
Timm M. Reissig, Swetlana Ladigan-Badura, Anja Steinberg, Abdelouahid Maghnouj, Ting Li, Berlinda Verdoodt, Sven T. Liffers, Michael Pohl, Heiner Wolters, Christian Teschendorf, Richard Viebahn, Jakob Admard, Nicolas Casadei, Andrea Tannapfel, Wolff Schmiegel, Stephan A. Hahn, Deepak B. Vangala
Summary: This study investigated the efficacy of vertical inhibition of the RAS-pathway in patient-derived xenograft tumors with primary KRAS mutation. The results showed that vertical inhibition therapy induced stable disease or partial response in the majority of models, with long-lasting responses and a low incidence of secondary resistance. Molecular analysis revealed that transcriptional reprogramming activating the RAS pathway drove primary and secondary resistance in a substantial fraction of tumors.
MOLECULAR ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Pashtoon Murtaza Kasi, Manuel Hidalgo, Mehraneh D. Jafari, Heather Yeo, Lea Lowenfeld, Uqba Khan, Alana T. H. Nguyen, Despina Siolas, Brandon Swed, Jini Hyun, Sahrish Khan, Madeleine Wood, Benjamin Samstein, Juan P. Rocca, Allyson J. Ocean, Elizabeta C. Popa, Daniel H. Hunt, Nikhil P. Uppal, Kelly A. Garrett, Alessio Pigazzi, Xi Kathy Zhou, Manish A. Shah, Erika Hissong
Summary: This study reports exceptional responses observed in patients with pMMR/MSS colon and rectal cancer treated with neoadjuvant botensilimab (BOT) and balstilimab (BAL). The findings have important implications for clinical trial designs using neoadjuvant immunotherapy and potentially sparing patients chemotherapy.
Article
Obstetrics & Gynecology
Stephan Hahn, Sabine Koerber, Bernd Gerber, Johannes Stubert
Summary: Background: Women after gestational diabetes mellitus (GDM) are at increased risk for development of GDM recurrence. Objective: To evaluate factors for prediction of risk of recurrence. Methods: Retrospective cohort study including 159 women with GDM and a subsequent pregnancy. Logistic regression models were used to analyze putative risk factors for GDM recurrence. Results were compared to age-matched women without GDM. Results: The overall risk of GDM recurrence was 72.3%. Risk factors for recurrence included high pregravid BMI, positive family history, and insulin treatment during the index pregnancy. Cesarean section delivery (index pregnancy) showed borderline significance. Interpregnancy weight gain, excessive weight gain during the index pregnancy, and fetal outcome were not predictive. Neonates after GDM had a higher frequency of transfer to intensive care unit compared to controls. The best combined risk model for prediction of GDM recurrence included positive family history and high pregravid BMI. Conclusions: Positive family history of diabetes mellitus with overweight or obesity increases the risk of GDM recurrence. Normalization of pregravid BMI is an effective approach to reduce the risk of GDM recurrence.
ARCHIVES OF GYNECOLOGY AND OBSTETRICS
(2023)
Article
Biochemistry & Molecular Biology
Pashtoon Murtaza Kasi, Manuel Hidalgo, Mehraneh D. Jafari, Heather Yeo, Lea Lowenfeld, Uqba Khan, Alana T. H. Nguyen, Despina Siolas, Brandon Swed, Jini Hyun, Sahrish Khan, Madeleine Wood, Benjamin Samstein, Juan P. Rocca, Allyson J. Ocean, Elizabeta C. Popa, Daniel H. Hunt, Nikhil P. Uppal, Kelly A. Garrett, Alessio Pigazzi, Xi Kathy Zhou, Manish A. Shah, Erika Hissong
Summary: Neoadjuvant botensilimab and balstilimab showed exceptional responses in patients with locally advanced mismatch repair proficient/microsatellite stable colon and rectal cancer. The observed rapid immune response pattern has not been previously described. Spatial biology analyses revealed the mechanism of action of botensilimab.