Protein S-nitrosylation (SNO), emerging as an important posttranslational modification, involves covalent addition of nitric oxide (NO) to the sulfur atom of cysteine in proteins. Accumulated evidence suggests that protein SNO plays crucial roles in pathophysiological mechanisms in cancer, which is attracting great attention. However, there are still controversies about whether S-nitrosylated proteins act as oncogenic proteins or tumor suppressors in cancer. In this review, we provide an overview of the early and latest evidence regarding the underlying mechanism and dual roles of SNO in cancer, in an effort to clarify its contribution in tumor progression. It has been well established that S-nitrosylated proteins restrain tumor progression in several types of cancer, while they have exhibited activities in promoting cell proliferation and inhibiting apoptosis in some other kinds of cancer. Interestingly, emerging evidence also has highlighted both its anti-cancer and pro-tumorigenic roles in several other cancer diseases. Finally, current limitations and future research prospects are presented. The overview of targeting SNO in cancer will provide new opportunities for drug development through in-depth exploration of SNO-mediated signaling pathways.

Adenosine alterations to RNA, which are largely determined by RNA modification writers (RMWs), are critical for cancer growth and progression. These RMWs can catalyze different types of adenosine modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), alternative polyadenylation (APA), and adenosine-to-inosine (A-to-I) RNA editing. These modifications have profound effects on gene expression and function, such as immune response, cell development. Despite this, the clinical effects of RMW interactive genes on these cancers remain largely unclear. A comprehensive analysis of the clinical impact of these epigenetic regulators in pan-cancer requires further comprehensive exploration. Here, we systematically profiled the molecular and clinical characteristics of 26 RMWs across 33 cancer types using multi-omics datasets and validated the expression level of some RMWs in various cancer lines. Our findings indicated that a majority of RMWs exhibited high expression in diverse cancer types, and this expression was found to be significantly associated with poor patient outcomes. In the genetic alterations, the amplification and mutation of RMWs were the dominant alteration events. Consequently, the RNA Modification Writer Score (RMW score) was established as a means to assess the risk of RMWs in pan-cancer. We found that 27 of 33 cancers had significantly higher scores compared with normal tissues, and it was significantly correlated with prognosis. We also evaluated their impact on the tumor microenvironment and the response to immunotherapy and targeted therapy. These findings verified the important role of RMWs in different aspects of cancer biology, and provided biomarkers and personalized therapeutic targets for cancer.

Breast cancer, as a malignant tumor with easy metastasis and poor prognosis, threatens the health of women around the world. Increasing studies have shown that the Bcl-2 family of apoptosis-related proteins is often expressed abnormally in breast cancer. The Bcl-2 homology 3 (BH3) mimetic peptide can bind and neutralize Bcl-2, preventing its binding to the apoptosis "effector" proteins Bak and Bax, thereby promoting the apoptosis process. However, there is a lack of effective intracellular delivery system for BH3 to exert its biological activity. Therefore, this study utilized an activatable supercharged polypeptide (ASCP) tumor-targeted delivery platform based on pH and protease response to achieve the targeted release of BH3 at the tumor site. Ultimately, intracellular delivery of BH3 was achieved and induced apoptosis of breast tumor cells, preventing the development of breast cancer.

Background: Hepatocellular carcinoma (HCC) stands out as one of the most lethal cancers globally, given its complexity, recurrence following surgical resection, metastatic potential, and inherent heterogeneity. In recent years, researchers have systematically elucidated the significance of long non-coding RNA (lncRNA) in the initiation and progression of HCC. The introduction of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases has significantly enhanced the prognostic assessment of HCC. However, the association between HCC and cell senescence has been infrequently explored in the literature. Method: We downloaded liver hepatocellular carcinoma (LIHC)-related messenger RNA and lncRNA expression levels from TCGA. Correlation analysis, Cox regression, and least absolute shrinkage and selection operator (LASSO) regression analysis were employed to validate the lncRNA risk model associated with cellular aging. Comparing the infiltration of diverse immune cells enabled the identification of distinct differences in the immunological microenvironments of the two risk groups. Subsequently, we conducted a real-time polymerase chain reaction (qPCR) experiment to confirm the accuracy of the selected lncRNAs. Results: A predictive framework for HCC was constructed based on the expression levels of five lncRNAs. Multivariate and univariate Cox regression analyses revealed that lncRNA signatures associated with senescence were independently correlated with an increased risk of HCC. Additionally, the nomogram also provides a more refined and sensitive model. Further investigation into the variations in immune cells and functions between the high-risk and low-risk groups was conducted. Subsequently, a qPCR experiment results revealed underexpression of AC068756.1, AC090578.1, AC145343.1, and LINC0022 in Huh7 and LM3 cells. In contrast, AP003392.4 did not exhibit a significant difference between Huh7 and control cells. Conclusion: The prognostic features and nomogram, consisting of five aging-related lncRNAs (AC068756.1, AC090578.1, AC145343.1, AP003392.4, and LINC00221), may be useful in predicting the overall survival of HCC.

Background: Bladder cancer (BLCA), particularly invasive BLCA, has become a medical burden worldwide as it is associated with recurrence and easy metastasis. There are specific differences in the expression of various miRNAs in tumor and normal tissues. Hence, miRNAs can be used as biomarkers for tumor diagnosis and prognostic evaluation. The current study aimed to predict the downstream target genes of BLCA-related miRNAs and explore their association with immune infiltration. Method: Data on BLCA-related mRNA and miRNA expression levels were downloaded from The Cancer Genome Atlas. Correlation analysis and Cox regression analysis were performed to validate the miRNA risk model. The infiltration of various immune cells should be compared to determine the distinct differences between the immunological microenvironment of the two risk groups. Results: A predictive framework of BLCA was established using the expression levels of two miRNAs. Cox regression analysis showed that the low-risk group had a better prognosis. Then, the target genes of miRNA were predicted, and the target genes were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Moreover, variations in immune cells and functions between the high- and low-risk groups were assessed. Conclusion: The prognostic features composed of two associated miRNAs (MIR-25, MIR-548AN) may help predict the overall survival of BLCA.

Cancer, a global health menace, continues to pose significant challenges in terms of incidence and mortality, necessitating innovative therapeutic strategies. Despite existing treatments, the limitations persist, prompting a quest for novel approaches. The emergence of immunotherapy marked a transformative era in solid tumor treatments, yet its efficacy is constrained by adverse effects. Concurrently, the integration of advanced technologies into cancer treatment explores the vast potential residing at the molecular level through gene analysis and manipulation. This review articulates the role of state-of-the-art genome editing technology, notably clustered regularly interspaced short palindromic repeats (CRISPR-Cas9), in overcoming the constraints of immunotherapy for cancers. Unveiling the intricacies of CRISPR-Cas9-mediated genome editing, the review introduces the formidable CRISPR toolbox. A spotlight is cast on the transformative impact of CRISPR-induced double-strand breaks (DSBs) on cancer immunotherapy, encompassing knockout and knock-in strategies. The utilization of CRISPR/Cas9 technology in pre-clinical cancer research has demonstrated notable success; however, its transition to the clinical setting remains in the nascent stages of development. This review aims to elucidate the fundamental aspects of CRISPR technology and offer a comprehensive survey of its existing applications while outlining its prospective role in the realm of cancer therapies. Through an exploration of CRISPR's mechanisms, current applications, and anticipated future potentials, this review provides valuable insights into the evolving landscape of CRISPR-based cancer treatment strategies.

Cancer, a pervasive threat to human health, presents formidable challenges to traditional treatment approaches. Tumor immunotherapy has emerged as a promising strategy for combating malignancies by bolstering the body's immune response to thwart tumor metastasis and recurrence. Nonetheless, the intricacies of tumors, patient heterogeneity, and the presence of tumor-immunosuppressive microenvironments have limited the overall efficacy of immunotherapy, achieving only approximately a 20% success rate. In recent years, nanomaterials have garnered increasing attention in the realm of tumor immunotherapy due to their inherent advantages, such as excellent biocompatibility, precise targeting, and controlled drug release. Nanomaterials empower immunostimulatory molecules and therapeutic agents with the ability to specifically target tumors, amplify drug accumulation at tumor sites, facilitate local immune modulation, alleviate immunosuppressive microenvironments, and thereby enhance the effectiveness of tumor immunotherapy. This review provides an overview of the current state of immunotherapy and offers insights into the ongoing research progress surrounding various nanomaterials aimed at augmenting the efficacy of immunotherapy.

Parkinson’s Disease (PD) is a prevalent progressive neurodegenerative condition affecting millions globally. Research has found that individuals with PD have a reduced risk of certain cancers, such as colon, lung, and rectal cancers, but an increased risk of brain cancer. Therefore, there is an urgent need for the development of advanced PD diagnostic methods and for investigating the relationships between risk factors, such as lifestyle due to handedness associated with various types of cancers. Recent ad- vancements in magnetic resonance imaging have enhanced PD diagnosis, reducing misdiagnosis and facilitating more accurate disease progression monitoring. Nevertheless, challenges exist, particularly in the distinction of PD between left-handed and right-handed patients over time. This survey provides an overview of contemporary deep learning-based imag- ing analysis methodologies, encompassing both non-longitudinal and lon- gitudinal contexts. We also explore existing limitations and prospects for refinement to gain deeper insights. These insights are poised to inform the development of personalized treatment strategies for PD patients while elucidating the current disparities between deep learning models and their efficacious implementation in clinical practice.

The latent transforming growth factor-beta (TGF-β) binding protein 1 (LTBP1) has been implicated in various cellular processes, but its role in triple-negative breast cancer (TNBC) remains unclear. In this study, we investigated the impact of LTBP1 on TNBC progression and its underlying mechanisms. Analysis of online datasets revealed elevated LTBP1 mRNA expression in breast cancer tissues compared to normal adjacent tissues. Kaplan-Meier Plotter analysis indicated that high LTBP1 expression was negatively correlated with relapse-free survival (RFS), distant-metastasis free survival (DMFS), and overall survival (OS) of breast cancer patients. Additionally, LTBP1 mRNA levels were associated with chemotherapy resistance. Functional assays in TNBC cells demonstrated that LTBP1 knockdown suppressed cell proliferation, induced apoptosis, and attenuated migration and invasion. In vivo studies confirmed that LTBP1 knockdown inhibited tumor growth in a xenograft mouse model. Mechanistically, LTBP1 positively correlated with genes involved in signaling regulation and organelle organization, with significant associations to GTPase binding and the RhoA/ROCK pathway. LTBP1 knockdown reduced RhoA activity and phosphorylation of Myosin Light Chain 2 (MLC2), suggesting inhibition of the RhoA/ROCK signaling pathway. Moreover, activation of the RhoA/ROCK pathway partially rescued the effects of LTBP1 knockdown on TNBC cell proliferation, apoptosis, migration, and invasion. In conclusion, our findings suggest that LTBP1 promotes TNBC progression through activation of the RhoA/ROCK signaling pathway, highlighting its potential as a therapeutic target for TNBC.

Metadherin (MTDH), also known as LYRIC or AEG-1, is an oncogene that enhances tumor progression, metastasis, drug resistance, and immune escape in various cancers by modulating multiple oncogenic pathways, including NF-κB, PI3K/AKT, Wnt/β-catenin, MAPK, and AMPK. Due to the unknown of the complete structure of MTDH, the deep mechanisms of MTDH and selective inhibitors targeting MTDH remain to be explored. The Protein-Protein interaction (PPI) with the Staphylococcal nuclease domain containing 1 (SND1) is a crucial mechanism underlying the function of MTDH. Current studies have demonstrated that inhibitors, including antisense oligonucleotides, peptides, and small molecules targeting MTDH or MTDH-SND1 interactions, provide novel strategies to inhibit the oncogenetic effects of MTDH. This review summarizes and discusses the structure, function, and regulation of MTDH in cancers, providing the potential therapeutic perspectives of MTDH or MTDH-SND1 PPI for drug discovery.

Approximately 28 million individuals in the United States face the risk of developing precancerous colonic adenomas (polyps) and potentially progressing to colorectal cancer (CRC). While a promising strategy for CRC prevention involves pharmacological intervention, such as cancer chemoprevention or interception, currently, there are no FDA-approved drugs capable of preventing the formation or progression of adenomas to adenocarcinoma. Numerous clinical, epidemiological, and preclinical studies have offered compelling evidence supporting the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in CRC chemoprevention. However, the prolonged use of NSAIDs is not FDA-approved due to potential life-threatening toxicities resulting from cyclooxygenase (COX) inhibition and the depletion of physiological prostaglandins. Despite indications that the COX inhibitory activity of NSAIDs may not be essential for their antineoplastic effects, the absence of a well-defined target impeded the development of derivatives that do not inhibit COX. Earlier research suggests that the inhibition of cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) may be responsible, at least in part, for the antineoplastic activity of the NSAID sulindac. This could potentially offer a novel target for CRC chemoprevention. To identify the cGMP PDE isozyme(s) contributing to the antineoplastic activity of sulindac, we synthesized a chemically diverse library of over 1500 compounds, all sharing the indene scaffold of sulindac. Subsequently, we screened these compounds for their impact on cancer cell growth and PDE inhibitory activity. From this screening, a series of lead compounds emerged. These compounds lacked COX-1 and COX-2 inhibitory activity, surpassing sulindac in potency to inhibit CRC cell growth. Importantly, they demonstrated greater selectivity by not affecting normal cell growth. Through chemical optimization, we identified several development candidates that selectively inhibit PDE5 and/or PDE10. These compounds activate cGMP/PKG signaling, suppressing Wnt/β-catenin transcription. This action counters the growth advantages resulting from APC or CTNNB1 mutations, which are responsible for most human CRCs. This review delves into the scientific literature supporting PDE5 and/or PDE10 as potential targets for CRC chemoprevention or interception. Our findings suggest a promising avenue for developing drugs that may effectively intervene in the progression of colorectal cancer, offering hope for improved preventive strategies in the future.

Ferroptosis, a recently identified form of programmed cell death, is characterized by the accumulation of lipid peroxidation, reactive oxygen species, and elevated free iron levels, involving the regulation of glutathione metabolism, iron metabolism, lipid metabolism, and oxidative stress biology. Tumor metastasis, a critical hallmark of malignancy and a key contributor to cancer recurrence and mortality, has been extensively linked to iron dysregulation, highlighting the potential of agents inducing iron-mediated cell death as promising strategies for preventing and treating metastasis. This review offers a comprehensive understanding the regulatory mechanisms underlying ferroptosis and its crucial role in the three distinct stages of metastasis: invasion, circulation, and colonization.

The paramount prerequisite for effective anti-cancer drugs is their ability to eradicate malignant cells while sparing non-cancer cells. The divergence in properties between malignant and non-cancer cells establishes a "therapeutic window," a critical consideration for achieving desirable treatment outcomes. Central to this is the imperative of a cancer drug's "selectivity and specificity." Taxanes, a pivotal class of successful anti-cancer drugs, continue to serve as the linchpin of cancer treatment due to their efficacy across a spectrum of cancer types. Operating as broad-spectrum chemotherapeutic agents, taxanes exert cytotoxic effects on proliferative cancer cells by binding to and stabilizing microtubules, disrupting mitosis, inducing mitotic catastrophe, and resulting in cell death. The distinct proliferative nature of cancer cells, as opposed to less proliferative non-cancer cells, affords taxanes a measure of specificity and selectivity. Nevertheless, sporadic yet recurring evidence suggests that taxanes also operate through non-mitotic mechanisms. Taxanes' binding and stabilization of microtubules lead to micronucleation and subsequent cell death, impacting both mitotic and non-mitotic cells. Recent discoveries indicate that the flexible and weakened nuclear envelope of malignant cells renders them sensitive to taxane-mediated micronucleation and cell death during various phases of the cell cycle. Conversely, non-cancerous cells typically exhibit a more robust and sturdy nuclear envelope, rendering them more tolerant to taxane-induced nuclear envelope fragmentation and subsequent micronucleation and cell death. The expression levels of nuclear envelope structural proteins, particularly Lamin A/C, emerge as indicators of taxane sensitivity. This evolving understanding underscores that nuclear envelope malleability, in conjunction with a high proliferation rate, is a pivotal determinant of taxane specificity and selectivity against malignant cells. These insights necessitate reconsidering oncological strategies to augment taxane efficacy, overcome resistance, and mitigate side effects.

Despite the advantages of nanoscale drug delivery systems, traditional nanoparticles often encounter challenges such as detection and elimination by the immune system. To circumvent these limitations, scientists have created biomimetic nanoparticles that extend circulation time, decrease clearance rates, and optimize drug delivery. The integration of cell membranes onto nanoparticle surfaces yields Cell Membrane-coated Nanoparticles (CMNPs) that exhibit behavior akin to actual cells while offering superior structural robustness and stability. A variety of cell membranes, including those of red blood cells, white blood cells, and cancer cells, lend unique properties and targeting capabilities to CMNPs. This review outlines the diagnostic and therapeutic roles of CMNP-based drug delivery systems in oncology and contemplates their possible clinical impact.

Nanomaterials have shown great potential in anti-tumor applications and are currently the focus of research. This review article aims to provide a comprehensive overview of the challenges encountered in oncology treatment and how nanomaterials are being utilized to overcome these obstacles. The authors discuss the limitations of conventional treatments, including limited efficacy, side effects, and toxicity issues. They highlight the importance of early tumour diagnosis and personalized treatment plans, as well as the need for innovative therapeutic approaches such as targeted therapy, immunotherapy, and gene therapy. The article primarily focuses on how nanomaterials can be engineered to achieve specific recognition and aggregation within tumour tissues through surface modifications involving targeting molecules such as antibodies, peptides, and receptor ligands. This surface modification technique facilitates improved targeting in the targeting of photodynamic therapy, while minimizing harm to normal tissues. The authors also discuss the potential and future prospects of nanomaterials in tumour therapy, including breakthroughs in their application, biosafety concerns, biocompatibility issues, preparation processes, clinical translation challenges, interdisciplinary cooperation, international exchange, relevant regulations and ethical guidelines. Overall, this review highlights the substantial potential of nanomaterials in oncology treatment, emphasizing the need for careful consideration of safety concerns to ensure their safe and effective application. The authors conclude that strengthening interdisciplinary cooperation and international exchange will contribute to the healthy development of nanomaterials in oncology treatment.

Tripartite motif-containing (TRIM) proteins consist of over 80 proteins, the majority of which exhibit E3 ubiquitin ligase activity. E3 ligases have a critical role in various cellular processes by specifically recognizing and ubiquitinating substrate proteins to promote their proteasomal degradation or alter their activities. Numerous studies have indicated that TRIMs are involved in carcinogenesis through various mechanisms. However, the regulatory mechanisms delimitating TRIMs’ function as E3 ligases has not yet been specifically addressed in a previous review article. In this review, we focus on recent advancements in understanding how certain TRIMs function solely as E3 ligases during cancer cell proliferation, apoptosis, and metastasis. We comprehensively summarize the target proteins of TRIMs involved in disordered signaling pathways such as Wnt/β-catenin, PI3K/AKT, NF-κB, p53, ERK, and STAT3, as well as those regulating the cell cycle and glycolysis. Following ubiquitination modification by TRIM E3 ligases, these target proteins either undergo proteasome-mediating degradation, maintain steady levels, or get activated/inactivated. This review provides a foundation for the development of E3 ligase-based cancer treatments.

Objective: The DSS was utilized to construct colitis model of mouse. The colitis mice were colonized with gut microbiota. The effects of gut microbial metabolites on colitis were studied. The mechanisms of gut microbial metabolites to improve intestinal immunity were also further explored. Methods: The male BALB/c mice were selected to construct colitis mouse model with DSS and colonized with gut microbiota. The content of short-chain fatty acids in intestinal metabolites of mice during modeling were detected with GC-MS. After the mice were sacrificed, the colon tissue was stained to observe the colitis in different groups of mice. The contents of IL-22 and IL-17 in colon tissue was determined with ELISA method. To study the mechanism of relieving colitis, qRT-PCR and western blotting were used to study the horizontal of Ffar2 gene and pSTAT3 and pAKT in colon tissue, respectively. The congenital lymphocytes were isolated and purified, and the migration ability of the congenital lymphocytes was examined by cell scratch plane migration test. Results: The colonization of the gut microbiota had significant effects on the contents of short-chain fatty acids in the intestinal metabolites of colitis mice, of which the effect on the content of acetic acid and butyric acid was more significant. The colonization of gut microbiota could effectively relieve colitis in mice and effectively promote the secretion of IL-22 in colon tissue. Studying the remission mechanism indicated that colonization of gut microbiota with colitis could effectively promote the expression of Ffar2 gene in colon tissue and increase the expression of pSTAT3 and pAKT protein. The migration ability of the lymphocyte was significantly upregulated in the model group compared with the other groups, demonstrating that DSS can effectively activate the lymphocyte; The migration of congenital lymphocyte in the experimental group was significantly alleviated than that in the model group, but it was up-regulated than that in the positive control group, and the colonic tissue of the positive control group was similar to that of the normal group. Conclusion: The short-chain fatty acids in the intestinal flora metabolites can promote the gene expression of the metabolite-sensitive receptor Ffar2. The effective combination of short-chain fatty acids and Ffar2 receptors can promote the phosphorylation of STAT3 and AKT proteins, effectively promote the secretion of IL-22 in intestinal ILC3 cells, alleviate colitis in mice, and thereby improve their intestinal immune function.

Macrophages are a type of white blood cells that can exist in two different functional states, known as M1 and M2. M1 macrophages secrete pro-inflammatory cytokines that can promote tumor growth and metastasis, whereas M2 macrophages secrete anti-inflammatory cytokines that can inhibit tumor progression. This phenomenon, referred to as macrophage polarization, has been implicated in the development and progression of cancer. Furthermore, macrophage polarization is currently being investigated in the context of COVID-19 severity. It is believed that M1 macrophages may contribute to the excessive inflammation observed in severe COVID-19 cases, while M2 macrophages may confer protection against the disease. Hence, comprehending the role of macrophage polarization in both cancer and COVID-19 has the potential to enhance treatment strategies for both conditions.

Machine learning is playing an increasingly important role in the healthcare industry by transforming the way cancer is diagnosed and treated. By analyzing patient data, genomic data, and imaging data, machine learning algorithms can identify molecular signatures that distinguish cancer patients from healthy patients. Biomarkers that can accurately detect and diagnose cancer can be identified through analysis of these data sources. Additionally, personalized cancer therapies can be developed by identifying the most effective treatments based on individual patient characteristics and cancer type. Some of the machine learning techniques used for cancer biomarker discovery include deep learning and support vector machines, which can respectively identify complex patterns in data and classify data to identify relevant biomarkers. The benefits of using machine learning for cancer biomarker discovery are significant, including more precise and personalized treatments, improved patient outcomes, and the potential to transform cancer diagnosis and treatment. However, there are also challenges associated with using machine learning for cancer biomarker discovery, such as data collection and privacy issues, as well as the need for more powerful computational resources. This article explores the potential of machine learning in cancer biomarker discovery and argues that ongoing research in this field has the potential to revolutionize cancer diagnosis and treatment. Future research directions should focus on further developing machine learning algorithms and effective data collection and privacy protocols.

The stages of liver fibrosis can reflect the severity of chronic viral hepatitis and the probability of liver cancer. Biopsy is still regarded as the reference for staging fibrosis, but the invasive method is not suitable for first-line screening. In recent years, noninvasive methods for detecting virus-driven liver fibrosis have been developed rapidly, which mainly include biological (serum biomarkers indexes) and physical (imaging assessment of liver stiffness) strategies. In this review, we introduce these noninvasive methods, enumerate their diagnosis performances and discuss the role of ferroptosis. At last, we propose directions for future researches.