() is a tumour suppressor gene and has a role in inhibiting the oncogenic AKT signalling pathway by dephosphorylating phosphatidylinositol 3,4,5-triphosphate (PIP) into phosphatidylinositol 4,5-bisphosphate (PIP). The function of PTEN is regulated by different mechanisms and inactive PTEN results in aggressive tumour phenotype and tumorigenesis. Identifying targeted therapies for inactive tumour suppressor genes such as has been challenging as it is difficult to restore the tumour suppressor functions. Therefore, focusing on the downstream signalling pathways to discover a targeted therapy for inactive tumour suppressor genes has highlighted the importance of synthetic lethality studies. This review focuses on the potential synthetic lethality genes discovered in PTEN-inactive cancer types. These discovered genes could be potential targeted therapies for PTEN-inactive cancer types and may improve the treatment response rates for aggressive types of cancer.
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http://dx.doi.org/10.1016/j.gendis.2022.12.015 | DOI Listing |
Front Microbiol
January 2025
Departments of Otorhinolaryngology-Head and Neck Surgery and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Oncogenic gamma herpesviruses, including Epstein-Barr Virus (EBV) and Kaposi's Sarcoma-associated Herpesvirus (KSHV), are opportunistic cancer-causing viruses and induces oncogenesis through complex mechanisms, which involves manipulation of cellular physiology as well as epigenetic and epitranscriptomic reprogramming. In this review, we describe the intricate processes by which these viruses interact with the epigenetic machinery, leading to alterations in DNA methylation, histone modifications, and the involvement of non-coding RNAs. The key viral proteins such as EBNA1 and LMP1 encoded by EBV; LANA and vGPCR encoded by KSHV; play pivotal roles in these modifications by interacting with host factors, and dysregulating signaling pathways.
View Article and Find Full Text PDFSmall Methods
January 2025
Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, Zhejiang, 310018, China.
Colorectal cancer (CRC) remains a significant global health challenge, underscoring the need for innovative therapeutic strategies. Oncogenic miRNAs (oncomiRs) play a significant biological role in the initiation and progression of colorectal cancer. Inspired by the cooperative mechanisms of plant nanovirus, which employ multiple circular single-stranded DNA (CssDNA) genomes, it is hypothesized that the development and delivery of CssDNA to target oncomiRs would achieve therapeutic benefits in CRC.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Pharmacy and BioTechnology - FaBiT, Alma Mater Studiorum - University of Bologna, via Irnerio 48, Bologna, 40126, Italy.
Environmental endocrine disruptor chemicals (EDCs) have raised significant concerns due to their potential adverse effects on human health, particularly on the central nervous system (CNS). This study provides a comparative analysis of the effects of 17-alpha ethinyl estradiol (EE2) and diethyl phthalate (DEP) on neuronal cell proliferation and neurotoxicity. Using differentiated SH-SY5Y human neuronal cells, we evaluated cell viability, microRNA (miRNA) regulation, and RNA expression following exposure to subtoxic concentrations of EE2 and DEP.
View Article and Find Full Text PDFCancer Sci
January 2025
Department of Drug Discovery and Biomedical Sciences, Faculty of Medicine, Saga University, Saga, Japan.
DNA methylation is an enzyme-driven epigenetic modification that must be precisely regulated to maintain cellular homeostasis. Aberrant methylation status, especially hypermethylation of the promoter sites of tumor-suppressor genes, is observed in human malignancies and is a proven target for cancer therapy. The first-generation DNA demethylating agents, azacitidine and decitabine, are widely used for treating several hematological malignancies.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Triple-negative breast cancer (TNBC) is a difficulty and bottleneck in the clinical treatment of breast cancer due to a lack of effective therapeutic targets. Herein, we first report that secernin 2 (SCRN2), an uncharacterized gene in human cancer, acts as a novel tumor suppressor in TNBC to inhibit cancer progression and enhance therapeutic sensitivity to poly(ADP-ribose) polymerase (PARP) inhibition both in vitro and in vivo. SCRN2 is downregulated in TNBC through chaperone-mediated autophagic degradation, and its downregulation is associated with poor patient prognosis.
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