Rapid progress in molecular cancer biology coupled with the discovery of novel oncology drugs has opened new horizons for cancer target discovery. As one of the crucial signaling pathways related to ...tumorigenesis, hypoxia-inducible factor-1 (HIF-1) coordinates the activity of many transcription factors and their downstream molecules that impact tumor growth and metastasis. Accumulating evidence suggests that the transcriptional responses to acute hypoxia are mainly attributable to HIF-1α. Moreover, the overexpression of HIF-1α in several solid cancers has been found to be strongly associated with poor prognosis. Thus, pharmacological targeting of the HIF-1 signaling pathways has been considered as a new strategy for cancer therapy in the recent years. Although over the past decade, tremendous efforts have been made in preclinical studies to develop new HIF-1 inhibitors from natural products (reservoirs of novel therapeutic agents), to date, these efforts have not been successfully translated into clinically available treatments. In this review, we provide new insights into the bio-pharmacological considerations for selecting natural compounds as potential HIF-1 inhibitors to accelerate anti-cancer drug development. In addition, we highlighted the importance of assessing the dependency of cancer on HIF1A to shortlist cancer types as suitable disease models. This may subsequently lead to new paradigms for discovering more HIF-1 inhibitors derived from natural products and facilitate the development of potent therapeutic agents targeting specific cancer types.
As crucial antigen presenting cells, dendritic cells (DCs) play a vital role in tumor immunotherapy. Taking into account the many recent advances in DC biology, we discuss how DCs (1) recognize ...pathogenic antigens with pattern recognition receptors through specific phagocytosis and through non-specific micropinocytosis, (2) process antigens into small peptides with proper sizes and sequences, and (3) present MHC-peptides to CD4
and CD8
T cells to initiate immune responses against invading microbes and aberrant host cells. During anti-tumor immune responses, DC-derived exosomes were discovered to participate in antigen presentation. T cell microvillar dynamics and TCR conformational changes were demonstrated upon DC antigen presentation. Caspase-11-driven hyperactive DCs were recently reported to convert effectors into memory T cells. DCs were also reported to crosstalk with NK cells. Additionally, DCs are the most important sentinel cells for immune surveillance in the tumor microenvironment. Alongside DC biology, we review the latest developments for DC-based tumor immunotherapy in preclinical studies and clinical trials. Personalized DC vaccine-induced T cell immunity, which targets tumor-specific antigens, has been demonstrated to be a promising form of tumor immunotherapy in patients with melanoma. Importantly, allogeneic-IgG-loaded and HLA-restricted neoantigen DC vaccines were discovered to have robust anti-tumor effects in mice. Our comprehensive review of DC biology and its role in tumor immunotherapy aids in the understanding of DCs as the mentors of T cells and as novel tumor immunotherapy cells with immense potential.
Wheat yield is influenced by the number of ears per unit area, and manual counting has traditionally been used to estimate wheat yield. To realize rapid and accurate wheat ear counting, K-means ...clustering was used for the automatic segmentation of wheat ear images captured by hand-held devices. The segmented data set was constructed by creating four categories of image labels: non-wheat ear, one wheat ear, two wheat ears, and three wheat ears, which was then was sent into the convolution neural network (CNN) model for training and testing to reduce the complexity of the model.
The recognition accuracy of non-wheat, one wheat, two wheat ears, and three wheat ears were 99.8, 97.5, 98.07, and 98.5%, respectively. The model
reached 0.96, the root mean square error (RMSE) was 10.84 ears, the macro F1-score and micro F1-score both achieved 98.47%, and the best performance was observed during late grain-filling stage (
= 0.99, RMSE = 3.24 ears). The model could also be applied to the UAV platform (
= 0.97, RMSE = 9.47 ears).
The classification of segmented images as opposed to target recognition not only reduces the workload of manual annotation but also improves significantly the efficiency and accuracy of wheat ear counting, thus meeting the requirements of wheat yield estimation in the field environment.
Long non-coding RNAs (lncRNAs) are versatile regulators of gene expression and play crucial roles in diverse biological processes. Epithelial-mesenchymal transition (EMT) is a cellular program that ...drives plasticity during embryogenesis, wound healing, and malignant progression. Increasing evidence shows that lncRNAs orchestrate multiple cellular processes by modulating EMT in diverse cell types. Dysregulated lncRNAs that can impact epithelial plasticity by affecting different EMT markers and target genes have been identified. However, our understanding of the landscape of lncRNAs important in EMT is far from complete. Here, we summarize recent findings on the mechanisms and roles of lncRNAs in EMT and elaborate on how lncRNAs can modulate EMT by interacting with RNA, DNA, or proteins in epigenetic, transcriptional, and post-transcriptional regulation. This review also highlights significant EMT pathways that may be altered by diverse lncRNAs, thereby suggesting their therapeutic potential.
Long noncoding RNAs (lncRNAs) have been implicated in various important biological processes, however, its role in energy balance and obesity remains largely unknown.
Differentially expressed lncRNAs ...in the hypothalamus of diet-induced obesity (DIO) mice versus chow-fed mice were identified by RNA sequencing. Lentivirus-mediated overexpression and knockdown of a novel lncRNA, AK044061, were used to assess its role in energy balance and the development of DIO. RNA immunoprecipitation (RIP) and pull down assays were carried out to analyze the interaction between lncRNA AK044061 and RelA, an NF-κB subunit.
LncRNA AK044061 was upregulated in the hypothalamus of DIO mice. Acute intracerebroventricular (i.c.v.) infusion of glucose reduced the expression of lncRNA AK044061, whereas an overnight of fasting enhanced its expression. RNA in situ hybridization data showed that AK044061 was expressed in the neurons of the arcuate nucleus (ARC). Lentivirus-mediated overexpression of AK044061 in ARC cells, or in the neurons of the ARC nucleus led to an obesity-like phenotype and related metabolic disorders. Furthermore, knockdown of lncRNA AK044061 in Agouti-related peptide (AgRP)-expressing neurons mitigated DIO and its related metabolic dysregulations. In mechanism, we showed that lncRNA AK044061 was associated with RelA and could enhance the NF-κB reporter activity. The effect of lncRNA AK044061 on energy balance is mediated by NF-κB.
Our findings suggest that excessive lncRNA AK044061 in the ARC nucleus leads to energy imbalance and obesity. LncRNA AK044061 expressed in the AgRP neurons is important in the development of dietary obesity in mice.
Copper, an indispensable micronutrient, is implicated in numerous vital biological processes and is essential for all physiological activities. Recently, the discovery of a novel type of ...copper-dependent cell death, known as cuproptosis, has shed light on its role in cancer development. Extensive research is currently underway to unravel the mechanisms underlying cuproptosis and its correlation with various cancer types. In this review, we summarize the findings regarding the roles and mechanisms of cuproptosis in various cancer types, including colorectal cancer, lung cancer, gastric cancer, breast cancer, liver cancer and cutaneous melanoma. Furthermore, the effects of copper-related agents such as copper chelators and copper ionophores on cell proliferation, apoptosis, angiogenesis, tumor immunity, and chemotherapy resistance have been explored in cancer preclinical and clinical trials. These insights provide promising avenues for the development of prospective anticancer drugs aimed at inducing cuproptosis.
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•Dysregulated copper homeostasis links cuproptosis and cancer progression.•Cuproptosis influencing cancer cell proliferation, migration, autophagy, apoptosis, and angiogenesis.•Copper chelators and copper ionophores have crucial effects in exploring new approaches for tumor therapy.
Epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor involved in homeostatic regulation of normal cells and carcinogenesis of epithelial malignancies. With rapid development of the ...precision medicine era, a series of new therapies targeting EGFR are underway. Four EGFR monoclonal antibody drugs (cetuximab, panitumumab, nimotuzumab, and necitumumab) are already on the market, and a dozen other EGFR monoclonal antibodies are in clinical trials. Here, we comprehensively review the newly identified biological properties and anti-tumor mechanisms of EGFR monoclonal antibodies. We summarize recently completed and ongoing clinical trials of the classic and new EGFR monoclonal antibodies. More importantly, according to our new standard, we re-classify the complex evolving tumor cell resistance mechanisms, including those involving exosomes, non-coding RNA and the tumor microenvironment, against EGFR monoclonal antibodies. Finally, we analyzed the limitations of EGFR monoclonal antibody therapy, and discussed the current strategies overcoming EGFR related drug resistance. This review will help us better understand the latest battles between EGFR monoclonal antibodies and resistant tumor cells, and the future directions to develop anti-tumor EGFR monoclonal antibodies with durable effects.
Long non-coding RNAs (lncRNAs) play multifaceted roles in modulating gene expression under both physiological and pathological processes. The dysregulation of lncRNAs has been increasingly linked ...with many human diseases, including a plethora of cancers. Mounting evidence indicates that lncRNAs are aberrantly expressed in hepatocellular carcinoma (HCC) and can regulate HCC progression, as well as metastasis. In this review, we summarize the recent findings on the expanding roles of lncRNAs in modulating various functions of HCC, and elaborate on how can lncRNAs impact HCC metastasis and progression via interacting with chromatin, RNA, and proteins at the epigenetic, transcriptional, and post-transcriptional levels. This mini-review also highlights the current advances regarding the signaling pathways of lncRNAs in HCC metastasis and sheds light on the possible application of lncRNAs for the prevention and treatment of HCC.
As global population ageing accelerates, cancer emerges as a predominant cause of mortality. Long non-coding RNAs (lncRNAs) play crucial roles in cancer cell growth and death, given their involvement ...in regulating downstream gene expression levels and numerous cellular processes. Cell death, especially non-apoptotic regulated cell death (RCD), such as ferroptosis, pyroptosis and necroptosis, significantly impacts cancer proliferation, invasion and metastasis. Understanding the interplay between lncRNAs and the diverse forms of cell death in cancer is imperative. Modulating lncRNA expression can regulate cancer onset and progression, offering promising therapeutic avenues. This review discusses the mechanisms by which lncRNAs modulate non-apoptotic RCDs in cancer, highlighting their potential as biomarkers for various cancer types. Elucidating the role of lncRNAs in cell death pathways provides valuable insights for personalised cancer interventions.
Extracellular vesicles (EVs) are membrane-encapsulated vesicles released by almost all cell types, which participate in intercellular communication by delivering different types of molecular cargoes, ...such as non-coding RNAs (ncRNAs). Accumulating evidence suggests that tumor-derived EVs act as a bridge for intercellular crosstalk between tumor cells and surrounding cells, including immune cells. Tumor-derived EVs containing ncRNAs (TEV-ncRNAs) mediate intercellular crosstalk to manipulate immune responses and affect the malignant phenotypes of cancer cells. In this review, we summarize the double-edged roles and the underlying mechanisms of TEV-ncRNAs in regulating innate and adaptive immune cells. We also highlight the advantages of using TEV-ncRNAs in liquid biopsies for cancer diagnosis and prognosis. Moreover, we outline the use of engineered EVs to deliver ncRNAs and other therapeutic agents for cancer therapy.
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