Hepatocellular carcinoma (HCC) is among the primary reasons for fatalities caused by cancer globally, highlighting the need for comprehensive knowledge of its molecular aetiology to develop successful treatment approaches. The PI3K/Akt system is essential in the course of HCC, rendering it an intriguing candidate for treatment. Non-coding RNAs (ncRNAs), such as long ncRNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are important mediators of the PI3K/Akt network in HCC. The article delves into the complex regulatory functions of ncRNAs in influencing the PI3K/Akt system in HCC. The study explores how lncRNAs, miRNAs, and circRNAs impact the expression as well as the function of the PI3K/Akt network, either supporting or preventing HCC growth. Additionally, treatment strategies focusing on ncRNAs in HCC are examined, such as antisense oligonucleotide-based methods, RNA interference, and small molecule inhibitor technologies. Emphasizing the necessity of ensuring safety and effectiveness in clinical settings, limitations, and future approaches in using ncRNAs as therapies for HCC are underlined. The present study offers useful insights into the complex regulation system of ncRNAs and the PI3K/Akt cascade in HCC, suggesting possible opportunities for developing innovative treatment approaches to address this lethal tumor.
Glioblastoma (GB) remains a formidable challenge and requires new treatment strategies. The vital part of the Ubiquitin-proteasome system (UPS) in cellular regulation has positioned it as a potentially crucial target in GB treatment, given its dysregulation oncolines. The Ubiquitin-specific proteases (USPs) in the UPS system were considered due to the garden role in the cellular processes associated with oncolines and their vital function in the apoptotic process, cell cycle regulation, and autophagy. The article provides a comprehensive summary of the evidence base for targeting USPs as potential factors for neoplasm treatment. The review considers the participation of the UPS system in the development, resulting in the importance of p53, Rb, and NF-κB, and evaluates specific goals for therapeutic administration using midnight proteasomal inhibitors and small molecule antagonists of E1 and E2 enzymes. Despite the slowed rate of drug creation, recent therapeutic discoveries based on USP system dynamics hold promise for specialized therapies. The review concludes with an analysis of future wanderers and the feasible effects of targeting USPs on personalized GB therapies, which can improve patient hydration in this current and unattractive therapeutic landscape. The manuscript emphasizes the possibility of USP oncogene therapy as a promising alternative treatment line for GB. It stresses the direct creation of research on the medical effectiveness of the approach.
One of the main causes of death worldwide is lung cancer, which is largely caused by cigarette smoking. The crucial transcription factor NF-κB, which controls inflammatory responses and various cellular processes, is a constitutively present cytoplasmic protein strictly regulated by inhibitors like IκB proteins. Upon activation by external stimuli, it undergoes phosphorylation, translocates into the nucleus, and modulates the expression of specific genes. The incontrovertible association between pulmonary malignancy and tobacco consumption underscores and highlights a public health concern. Polycyclic aromatic hydrocarbons and nitrosamines, potent carcinogenic compounds present in the aerosol emitted from combusted tobacco, elicit profound deleterious effects upon inhalation, resulting in severe perturbation of pulmonary tissue integrity. The pathogenesis of smoking-induced lung cancer encompasses an intricate process wherein NF-κB activation plays a pivotal role, triggered by exposure to cigarette smoke through diverse signaling pathways, including those associated with oxidative stress and pro-inflammatory cytokines. Unraveling the participation of NF-κB in smoking-induced lung cancer provides pivotal insights into molecular processes, wherein intricate crosstalk between NF-κB and pathways such as MAPK and PI3K-Akt amplifies the inflammatory response, fostering an environment conducive to the formation of lung cancer. This study reviews the critical function of NF-κB in the complex molecular pathways linked to the initiation and advancement of lung carcinogenesis as well as potential treatment targets. See also the graphical abstract(Fig. 1).
Pyroptosis is an inflammatory programed cell death process that plays a crucial role in cancer therapeutic, while Gasdermin-D is a critical effector protein for pyroptosis execution. This review discusses the intricate interactions between Gasdermin-D and some non-coding RNAs (lncRNA, miRNA, siRNA) and their potential application in the regulation of pyroptosis as an anticancer therapy. Correspondingly, these ncRNAs significantly implicate in Gasdermin-D expression and function regarding the pyroptosis pathway. Functioning as competing endogenous RNAs (ceRNAs), these ncRNAs might regulate Gasdermin-D at the molecular level, underlying fatal cell death caused by cancer and tumor propagation. Therefore, these interactions appeal to therapeutics, offering new avenues for cancer treatment. It address this research gap by discussing the possible roles of ncRNAs as mediators of gasdermin-D regulation. It suggest therapeutic strategies based on the current research findings to ensure the interchange between the ideal pyroptosis and cancer cell death.
Pancreatic cancer is a highly fatal malignancy due to poor early detection rate and resistance to conventional therapies. This review examines the potential for liquid biopsy as a transformative technology to identify diagnostic and therapeutic targets in pancreatic cancer. Specifically, we explore emerging biomarkers such as exosomal non-coding RNAs (ncRNAs), circulating tumor DNA (ctDNA), and circulating tumor cells (CTCs). Tumor-derived exosomes contain nucleic acid and protein that reflect the unique molecular landscape of the malignancy and can serve as an alternative diagnostic approach vs traditional biomarkers like CA19-9. Herein we highlight exosomal miRNAs, lncRNAs, and other ncRNAs alongside ctDNA and CTC-based strategies, evaluating their combined ability to improve early detection, disease monitoring and treatment response. Furthermore, the therapeutic implications of ncRNAs such as lncRNA UCA1 and miR-3960 in chemoresistance and progression are also discussed via suppression of EZH2 and PTEN/AKT pathways. Emerging therapeutic strategies that target the immune response, epithelial-mesenchymal transition (EMT) and drug resistance are explored. This review demonstrates a paradigm shift in pancreatic cancer management toward personalized, less invasive and more effective approaches.
p16INK4a is a crucial tumor suppressor and regulator of cellular senescence, forming a molecular bridge between aging and cancer. Dysregulated p16INK4a expression is linked to both premature aging and cancer progression, where non-coding RNAs (ncRNAs) such as long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and small interfering RNAs (siRNAs) play key roles in modulating its function. These ncRNAs interact with p16INK4a through complex post-transcriptional and epigenetic mechanisms, influencing pathways critical to senescence and tumor suppression. In this review, we explore ncRNAs, including ANRIL, MIR31HG, UCA1, MALAT1, miR-24, miR-30, and miR-141, which collectively regulate p16INK4a expression, promoting or inhibiting pathways associated with cancer and aging. ANRIL and MIR31HG modulate p16INK4a silencing via interactions with polycomb repressive complexes (PRC), while miRNAs such as miR-24 and miR-30 target p16INK4a to influence cellular proliferation and senescence. This regulatory interplay underscores the therapeutic potential of ncRNA-targeted strategies to restore p16INK4a function. We summarize recent studies supporting that ncRNAs that control p16INK4a may be diagnostic biomarkers and therapeutic targets for age-related diseases and cancer.
Several molecular strategies based on targeted gene delivery systems have been developed in recent years; however, the CRISPR-Cas9 technology introduced a new era of targeted gene editing, precisely modifying oncogenes, tumor suppressor genes, and other regulatory genes involved in carcinogenesis. However, efficiently and safely delivering CRISPR-Cas9 to cancer cells across the cell membrane and the nucleus is still challenging. Using viral vectors and nanoparticles presents issues of immunogenicity, off-target effects, and low targeting affinity. Naturally, extracellular vesicles called exosomes have garnered the most attention as delivery vehicles in oncology-related CRISPR-Cas9 calls due to their biocompatibility, loading capacity, and inherent targeting features. The following review discusses the current progress in using exosomes to deliver CRISPR-Cas9 components, the approaches to load the CRISPR components into exosomes, and the modification of exosomes to increase stability and tumor-targeted delivery. We discuss the latest strategies in targeting recently accomplished in the exosome field, including modifying the surface of exosomes to enhance their internalization by cancer cells, as well as the measures taken to overcome the impacts of TME on delivery efficiency. Focusing on in vitro and in vivo experimentation, this review shows that exosome-mediated CRISPR-Cas9 can potentially treat cancer types, including pancreatic, lymphoma, and leukemia, for given gene targets. This paper compares exosome-mediated delivery and conventional vectors regarding safety, immune response, and targeting ability. Last but not least, we present the major drawbacks and potential development of the seemingly promising field of exosome engineering in gene editing, with references to CRISPR technologies and applications that may help make the target exosomes therapeutic in oncology.
Cell death is a fundamental process that needs to be maintained to balance cellular functions and prevent disease. There are several cell death pathways; however, apoptosis and parthanatos are the most prominent and have important roles in cancer biology. As an extremely well-regulated process, apoptosis removes damaged or abnormal cells via caspase activation and mitochondrial involvement. Unlike in the healthy cells, the loss of ability to induce apoptosis in cancer permits tumor cells to survive and multiply out of control and contribute to tumor progression and therapy resistance. On the contrary, parthanatos is a caspase-independent metabolic collapse driven by poly (ADP-ribose) polymerase 1 (PARP1) overactivation, translocation of apoptosis-inducing factor (AIF), and complete DNA damage. Several cancer models are involved with parthanatos. Deoxypodophyllotoxin (DPT) induces parthanatos in glioma cells by excessive ROS generation, PARP1 upregulation, and AIF nuclear translocation. Like in acute myeloid leukemia (AML), the cannabinoid derivative WIN-55 triggers parthanatos, and the effects can be reversed by PARP inhibitors such as olaparib. Developing cancer treatment strategies involving advanced cancer treatment strategies relies on the interplay between apoptosis and parthanatos. However, such apoptosis-based cancer therapies tend to develop resistance, so there is an urgent need to look into alternative pathways like parthanatos, which may not always trigger apoptosis. In overcoming apoptosis resistance, there is evidence that combining apoptosis-inducing agents, such as BH3 mimetics, with PARP inhibitors synergistically enhances cell death. Oxidative stress modulators have been found to promote the execution of parthanatic and apoptotic pathways and allow treatment. In this review, apoptosis and parthanatos are thoroughly compared at the molecular level, and their roles in cancer pathogenesis as related to cancer therapeutic potential are discussed. We incorporate recent findings to demonstrate that not only can parthanatos be used to manage therapy resistance and enhance cancer treatment via the combination of parthanatos and apoptosis but also that immunity and bone deposition can feasibly be employed against long-circulating cancer stem cells to treat diverse forms of metastatic cancers.
Parkinson's Disease (PD) is a complex neurological illness that causes severe motor and non-motor symptoms due to a gradual loss of dopaminergic neurons in the substantia nigra. The aetiology of PD is influenced by a variety of genetic, environmental, and cellular variables. One important aspect of this pathophysiology is autophagy, a crucial cellular homeostasis process that breaks down and recycles cytoplasmic components. Recent advances in genomic technologies have unravelled a significant impact of ncRNAs on the regulation of autophagy pathways, thereby implicating their roles in PD onset and progression. They are members of a family of RNAs that include miRNAs, circRNA and lncRNAs that have been shown to play novel pleiotropic functions in the pathogenesis of PD by modulating the expression of genes linked to autophagic activities and dopaminergic neuron survival. This review aims to integrate the current genetic paradigms with the therapeutic prospect of autophagy-associated ncRNAs in PD. By synthesizing the findings of recent genetic studies, we underscore the importance of ncRNAs in the regulation of autophagy, how they are dysregulated in PD, and how they represent novel dimensions for therapeutic intervention. The therapeutic promise of targeting ncRNAs in PD is discussed, including the barriers that need to be overcome and future directions that must be embraced to funnel these ncRNA molecules for the treatment and management of PD.