Article
Oncology
Bu-Fu Tang, Ruo-Chen Yan, Si-Wei Wang, Zhao -Chong Zeng, Shi-Suo Du
Summary: Maternal embryonic leucine zipper kinase (MELK) is a member of the AMPK protein family and is highly expressed in various cancers. It plays an important role in regulating tumor cell functions and the tumor microenvironment. Targeting MELK has shown promising results in anti-tumor therapy.
Article
Biology
Nahlah Makki Almansour
Summary: This study employed computer aided drug design approaches to identify potential binding molecules of MELK. Two drug molecules with high affinity binding to MELK were identified and showed stable binding free energy. The compounds exhibited stable dynamics and formed multiple hydrogen bonds with MELK active pocket residues. These compounds have potential for further investigation.
SAUDI JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Chemistry, Medicinal
Kang Le, Michael J. J. Soth, Jason B. B. Cross, Gang Liu, William J. J. Ray, Jiacheng Ma, Sunil G. G. Goodwani, Paul J. J. Acton, Virginie Buggia-Prevot, Onno Akkermans, John Barker, Michael L. L. Conner, Yongying Jiang, Zhen Liu, Paul McEwan, Jennifer Warner-Schmidt, Alan Xu, Matthias Zebisch, Cobi J. J. Heijnen, Brett Abrahams, Philip Jones
Summary: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant medical issue without sufficient treatment options. However, the discovery of DLK as a target presents a potential solution for treating neuronal injury and neurodegenerative diseases caused by CIPN. The development of potent DLK inhibitors, such as IACS-52825 (22), has shown promising results in reversing mechanical allodynia in mouse models of CIPN.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Zongqiang Hu, Yingpeng Zhao, Yuanyi Mang, Jiashun Zhu, Lu Yu, Li Li, Jianghua Ran
Summary: miR-21-5p promotes progression and sorafenib resistance in hepatocellular carcinoma by upregulating autophagy levels. Knockdown of miR-21-5p inhibits the development of sorafenib-resistant tumors through USP24-mediated SIRT7 ubiquitination.
Article
Cell Biology
Patricia de la Cruz-Ojeda, Tobias Schmid, Loreto Boix, Manuela Moreno, Victor Sapena, Juan M. Praena-Fernandez, Francisco J. Castell, Juan Manuel Falcon-Perez, Maria Reig, Bernhard Bruene, Miguel A. Gomez-Bravo, Alvaro Giraldez, Jordi Bruix, Maria T. Ferrer, Jordi Muntane
Summary: The study reveals that Sorafenib regulates a specific miRNA signature, where miR-200c-3p, miR-222-5p, and miR-512-3p have prognostic value and contribute to treatment response.
Article
Genetics & Heredity
Tamyres Mingorance Carvalho, Guillermo Ortiz Brasil, Tayana Schultz Jucoski, Douglas Adamoski, Rubens Silveira de Lima, Cleverton C. Spautz, Karina Furlan Anselmi, Patricia Midori Murobushi Ozawa, Iglenir Joao Cavalli, Jaqueline Carvalho de Oliveira, Daniela Fiori Gradia, Enilze Maria de Souza Fonseca Ribeiro
Summary: The study identified miR-320a and miR-4433b-5p as highly specific and sensitive biomarkers for distinguishing breast cancer from controls, regardless of sample source. In tissues, lower levels of miR-150-5p and higher levels of miR-142-5p were significant biomarkers. Combining these miRNAs in panels improved the ability to differentiate breast cancer patients from controls.
FRONTIERS IN GENETICS
(2022)
Article
Immunology
Kaifeng Guan, Qiuju Su, Kailin Kuang, Xiangge Meng, Xiang Zhou, Bang Liu
Summary: This study reveals that PRRSV infection subverts ER-phagy by downregulating FAM134B, which in turn promotes PRRSV replication. Furthermore, FAM134B-mediated ER-phagy activates interferon signaling to inhibit PRRSV replication.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, Research & Experimental
Fan Hu, Chengpeng Gong, Yongkang Gai, Dawei Jiang, Qingyao Liu, Sheng Wang, Mengmeng Hu, Rundong Pi, Hua Shu, Jia Hu, Xiaoli Lan
Summary: The study developed a F-18-radiolabeled tracer based on a small-molecule MELK inhibitor and evaluated its potential for PET imaging of MELK expression in TNBC. The tracer showed high uptake in MDA-MB-231 tumors, low uptake in MCF-7 tumors, and high specificity. These findings suggest promising clinical potential for selecting patients for MELK inhibitor therapy.
MOLECULAR PHARMACEUTICS
(2021)
Article
Medicine, Research & Experimental
Bei Zhou, Donghui Lu, Anqi Wang, Jie Cui, Li Zhang, Jian Li, Lulu Fan, Wei Wei, Jiatao Liu, Guoping Sun
Summary: The study revealed that endoplasmic reticulum stress promotes sorafenib resistance in hepatocellular carcinoma via the upregulation of PKM2 through the miR-188-5p/hnRNPA2B1 pathway. Targeting this pathway and ER stress could be a potential strategy to overcome sorafenib resistance in HCC treatment.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2021)
Article
Multidisciplinary Sciences
Ashley A. Hardeman, Yoo Jane Han, Tatyana A. Grushko, Jeffrey Mueller, Maria J. Gomez, Yonglan Zheng, Olufunmilayo I. Olopade
Summary: This study found that MELK gene expression is highly upregulated in aggressive forms of breast cancer, particularly in basal-like breast cancer (BLBC). The increase in MELK expression appears to be driven by gene copy number gains rather than epigenetic modifications. The findings suggest that MELK overexpression and copy number gains could be potential diagnostic and prognostic markers for identifying patients with more aggressive breast cancer.
Article
Medicine, Research & Experimental
Yongping Zhou, Yonggang Huang, Tu Dai, Zhiyuan Hua, Jian Xu, Yuting Lin, Lulu Han, Xiong Yue, Lichen Ho, Jinjing Lu, Xiaoming Ai
Summary: The silencing of TTN-AS1 in Sorafenib-resistant HCC cells induces apoptosis by enhancing sensitivity to Sorafenib, alleviating the anti-apoptotic effect of TTN-AS1 gene. This suggests TTN-AS1 as a potential therapeutic target for Sorafenib resistance in HCC.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Oncology
Akihiro Hirao, Yasushi Sato, Hironori Tanaka, Kensei Nishida, Tetsu Tomonari, Misato Hirata, Masahiro Bando, Yoshifumi Kida, Takahiro Tanaka, Tomoyuki Kawaguchi, Hironori Wada, Tatsuya Taniguchi, Koichi Okamoto, Hiroshi Miyamoto, Naoki Muguruma, Toshihito Tanahashi, Tetsuji Takayama
Summary: The study identified miR-125-5p as a key player in inducing sorafenib resistance in hepatocellular carcinoma by suppressing ataxin-1, inducing EMT, and promoting cancer stem cell properties, ultimately leading to a poor prognosis for patients.
Article
Biochemistry & Molecular Biology
Elena Tortosa, Arundhati Sengupta Ghosh, Qingling Li, Weng Ruh Wong, Trent Hinkle, Wendy Sandoval, Christopher M. Rose, Casper C. Hoogenraad
Summary: The phosphorylation and membrane localization of DLK, a component of MAPK, is crucial for its activation during neuronal stress responses. The recruitment of DLK to specific vesicles upon stress induces kinase activation, which is essential for neuronal survival and degeneration.
Article
Oncology
Xianguo Meng, Wei Li, Ziqi Meng, Yan Li
Summary: This study reveals the important role of a newly discovered circRNA, circBRWD3, in the tumorigenesis and progression of breast cancer. CircBRWD3 expression is upregulated in breast cancer tissues and is associated with poor prognosis. Mechanistically, circBRWD3 regulates the miR-142-3p, miR-142-5p, and RAC1/PAK1 signaling pathway to promote tumor formation and progression. Additionally, circBRWD3 expression is positively regulated by EIF4A3. These findings provide valuable scientific data for the early diagnosis and therapy of breast cancer patients.
Article
Cell Biology
Sukanya Shyamasundar, Seshadri Ramya, Deepika Kandilya, Dinesh Kumar Srinivasan, Boon Huat Bay, Suraiya Anjum Ansari, S. Thameem Dheen
Summary: Maternal diabetes is associated with increased risk of neurodevelopmental disorders in offspring. Hyperglycemia alters expression of genes and microRNAs in neural stem cells, including downregulation of methyl-CpG-binding protein-2 (Mecp2). miR-26b-5p controls Mecp2 expression and affects neurite outgrowth and synaptogenesis. These findings suggest that maternal diabetes disrupts synaptogenesis through miR-26b-5p/Mecp2 pathway, potentially leading to neurodevelopmental disorders.