RN7SL1 may be translated under oncogenic conditions.

RN7SL1 (RNA component of signal recognition particle 7SL1), a component of the signal recognition particle, is a non-coding RNA possessing a small ORF (smORF). However, whether it is translated into peptides is unknown. Here, we generated the RN7SL1-Green Fluorescent Protein (GFP) gene, in which the smORF of RN7SL1 was replaced by GFP, introduced it into 293T cells, and observed cells emitting GFP fluorescence. Furthermore, RNA-seq of GFP-positive cells revealed that they were in an oncogenic state, suggesting that RN7SL1 smORF may be translated under special conditions.

RNA methylation in inflammatory bowel disease.

RNA modifications, including the renowned m6A, have recently garnered significant attention. This chemical alteration, present in mRNA, exerts a profound influence on protein expression levels by affecting splicing, nuclear export, stability, translation, and other critical processes. Although the role of RNA methylation in the pathogenesis and progression of IBD and colorectal cancer has been reported, many aspects remain unresolved. In this comprehensive review, we present recent studies on RNA methylation in IBD and colorectal cancer, with a particular focus on m6A and its regulators. We highlight the pivotal role of m6A in the pathogenesis of IBD and colorectal cancer and explore the potential applications of m6A modifications in the diagnosis and treatment of these diseases.

Fat and proteolysis due to methionine, tryptophan, and niacin deficiency leads to alterations in gut microbiota and immune modulation in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is one of the intractable diseases. Nutritional components associated with IBD have been identified, and it is known that excessive methionine intake exacerbates inflammation, and that tryptophan metabolism is involved in inflammation. Analysis of the gut microbiota has also progressed, where Lactobacillus regulate immune cells in the intestine and suppress inflammation. However, whether the methionine and tryptophan metabolic pathways affect the growth of intestinal Lactobacillus is unknown. Here we show how transient methionine, tryptophan, and niacin deficiency affects the host and gut microbiota in mouse models of colitis (induced by dextran sodium sulfate) fed a methionine-deficient diet (1K), tryptophan and niacin-deficient diet (2K), or methionine, tryptophan, and niacin-deficient diet (3K). These diets induced body weight decrease and 16S rRNA analysis of mouse feces revealed the alterations in the gut microbiota, leading to a dramatic increase in the proportion of Lactobacillus in mice. Intestinal RNA sequencing data confirmed that the expression of several serine proteases and fat-metabolizing enzymes were elevated in mice fed with methionine, tryptophan, and niacin (MTN) deficient diet. In addition, one-carbon metabolism and peroxisome proliferator-activated receptor (PPAR) pathway activation were also induced with MTN deficiency. Furthermore, changes in the expression of various immune-related cytokines were observed. These results indicate that methionine, tryptophan, and niacin metabolisms are important for the composition of intestinal bacteria and host immunity. Taken together, MTN deficiencies may serve as a Great Reset of gut microbiota and host gene expression to return to good health.

High N6-methyladenosine-activated TCEAL8 mRNA is a novel pancreatic cancer marker.

N6-methyladenosine (m6A) is an RNA modification involved in RNA processing and widely found in transcripts. In cancer cells, m6A is upregulated, contributing to their malignant transformation. In this study, we analyzed gene expression and m6A modification in cancer tissues, ducts, and acinar cells derived from pancreatic cancer patients using MeRIP-seq. We found that dozens of RNAs highly modified by m6A were detected in cancer tissues compared with ducts and acinar cells. Among them, the m6A-activated mRNA TCEAL8 was observed, for the first time, as a potential marker gene in pancreatic cancer. Spatially resolved transcriptomic analysis showed that TCEAL8 was highly expressed in specific cells, and activation of cancer-related signaling pathways was observed relative to TCEAL8-negative cells. Furthermore, among TCEAL8-positive cells, the cells expressing the m6A-modifying enzyme gene METTL3 showed co-activation of Notch and mTOR signaling, also known to be involved in cancer metastasis. Overall, these results suggest that m6A-activated TCEAL8 is a novel marker gene involved in the malignant transformation of pancreatic cancer.

[Future Perspectives of Single-Cell RNA Sequencing in Cancer Research].

This review focuses on cancer, a serious health issue in modern society, and explores the advancements and applications of single-cell RNA sequencing(scRNA-seq)as an advanced technique for understanding its pathobiology. Cancer often arises due to genetic mutations or epigenetic changes, which manifest through fluctuations in gene expression. Therefore, transcriptome information(transcriptomics)plays an indispensable role in cancer research. In this field, there has been a shift from hybridization to next-generation sequencing, and the emergence of scRNA-seq technology enables the analysis of dynamic gene expression properties at the single-cell level. Consequently, significant advancements have been made in cancer research, including understanding complex intercellular variations and interactions, as well as revealing the roles of the tumor microenvironment and immune cells, and the contribution of non-coding RNAs. This review focuses on the progress and applications of scRNA-seq technology, providing an overview of new insights and prospects for cancer research and therapy.

The Link of mRNA and rRNA Transcription by PUF60/FIR through TFIIH/P62 as a Novel Therapeutic Target for Cancer.

The interaction between mRNA and ribosomal RNA (rRNA) transcription in cancer remains unclear. RNAP I and II possess a common N-terminal tail (NTT), RNA polymerase subunit RPB6, which interacts with P62 of transcription factor (TF) IIH, and is a common target for the link between mRNA and rRNA transcription. The mRNAs and rRNAs affected by FUBP1-interacting repressor (FIR) were assessed via RNA sequencing and qRT-PCR analysis. An FIR, a c-myc transcriptional repressor, and its splicing form FIRΔexon2 were examined to interact with P62. Protein interaction was investigated via isothermal titration calorimetry measurements. FIR was found to contain a highly conserved region homologous to RPB6 that interacts with P62. FIRΔexon2 competed with FIR for P62 binding and coactivated transcription of mRNAs and rRNAs. Low-molecular-weight chemical compounds that bind to FIR and FIRΔexon2 were screened for cancer treatment. A low-molecular-weight chemical, BK697, which interacts with FIRΔexon2, inhibited tumor cell growth with rRNA suppression. In this study, a novel coactivation pathway for cancer-related mRNA and rRNA transcription through TFIIH/P62 by FIRΔexon2 was proposed. Direct evidence in X-ray crystallography is required in further studies to show the conformational difference between FIR and FIRΔexon2 that affects the P62-RBP6 interaction.

Bridging the gap in cervical cancer screening for underserved communities: MCED and the promise of future technologies.

Cervical cancer screening is a critical public health measure, especially vital for underserved communities where disparities in access and outcomes are pronounced. Despite the life-saving potential of regular screening, numerous barriers-including geographical isolation, cultural and linguistic challenges, and socioeconomic factors-severely hinder accessibility for these populations. Multicancer early detection (MCED) tests emerge as a potentially effective intervention, offering a less invasive, more accessible approach that could transform how screenings are conducted. This paper explores the existing challenges in traditional cervical cancer screening methods, the potential of MCED tests to address these barriers, and the implications of these technologies for global health equity. Through a comprehensive review, we highlight the need for culturally sensitive, tailored interventions and the importance of effectively overcoming logistical and financial difficulties to implement MCED tests. Despite the promise shown by MCED tests, the paper acknowledges significant implementation challenges, including cost, logistical obstacles, and the need for cultural acceptance and validation studies. This study emphasizes the necessity for equitable MCED test implementation strategies, highlighting the potential of these innovative technologies to advance global health equity in cervical cancer prevention.

Revealing neuropilin expression patterns in pancreatic cancer: From single­cell to therapeutic opportunities (Review).

Pancreatic cancer, one of the most fatal types of human cancers, includes several non-epithelial and stromal components, such as activated fibroblasts, vascular cells, neural cells and immune cells, that are involved in different cancers. Vascular endothelial cell growth factor 165 receptors 1 [neuropilin-1 (NRP-1)] and 2 (NRP-2) play a role in the biological behaviors of pancreatic cancer and may appear as potential therapeutic targets. The NRP family of proteins serve as co-receptors for vascular endothelial growth factor, transforming growth factor ß, hepatocyte growth factor, fibroblast growth factor, semaphorin 3, epidermal growth factor, insulin-like growth factor and platelet-derived growth factor. Investigations of mechanisms that involve the NRP family of proteins may help develop novel approaches for overcoming therapy resistance in pancreatic cancer. The present review aimed to provide an in-depth exploration of the multifaceted roles of the NRP family of proteins in pancreatic cancer, including recent findings from single-cell analysis conducted within the context of pancreatic adenocarcinoma, which revealed the intricate involvement of NRP proteins at the cellular level. Through these efforts, the present study endeavored to further reveal their relationships with different biological processes and their potential as therapeutic targets in various treatment modalities, offering novel perspectives and directions for the treatment of pancreatic cancer.

Tissue-Resident Memory T Cells in Gastrointestinal Cancers: Prognostic Significance and Therapeutic Implications.

Gastrointestinal cancers, which include a variety of esophageal and colorectal malignancies, present a global health challenge and require effective treatment strategies. In the evolving field of cancer immunotherapy, tissue-resident memory T cells (Trm cells) have emerged as important players in the immune response within nonlymphoid tissues. In this review, we summarize the characteristics and functions of Trm cells and discuss their profound implications for patient outcomes in gastrointestinal cancers. Positioned strategically in peripheral tissues, Trm cells have functions beyond immune surveillance, affecting tumor progression, prognosis, and response to immunotherapy. Studies indicate that Trm cells are prognostic markers and correlate positively with enhanced survival. Their presence in the tumor microenvironment has sparked interest in their therapeutic potential, particularly with respect to immune checkpoint inhibitors, which may improve cancer treatment. Understanding how Trm cells work will not only help to prevent cancer spread through effective treatment but will also contribute to disease prevention at early stages as well as vaccine development. The role of Trm cells goes beyond just cancer, and they have potential applications in infectious and autoimmune diseases. This review provides a thorough analysis of Trm cells in gastrointestinal cancers, which may lead to personalized and effective cancer therapies.

Significance of signal recognition particle 9 nuclear translocation: Implications for pancreatic cancer prognosis and functionality.

Signal recognition particles (SRPs) are essential for regulating intracellular protein transport and secretion. Patients with tumors with high SRP9 expression tend to have a poorer overall survival. However, to the best of our knowledge, no reports have described the relationship between SRP9 localization and prognosis in pancreatic cancer. Thus, the present study aimed to investigate this relationship. Immunohistochemical staining for SRP9 using excised specimens from pancreatic cancer surgery cases without preoperative chemotherapy or radiotherapy showed that SRP9 was preferentially expressed in the nucleus of the cancerous regions in some cases, which was hardly detected in other cases, indicating that SRP9 was transported to the nucleus in the former cases. To compare the prognosis of patients with SRP9 nuclear translocation, patients were divided into two groups: Those with a nuclear translocation rate of >50% and those with a nuclear translocation rate of ≤50%. The nuclear translocation rate of >50% group had a significantly better recurrence­free survival than the nuclear translocation rate of ≤50% group (P=0.037). Subsequent in vitro experiments were conducted; notably, the nuclear translocation rate of SRP9 was reduced under amino acid­deficient conditions, suggesting that multiple factors are involved in this phenomenon. To further study the function of SRP9 nuclear translocation, in vitro experiments were performed by introducing SRP9 splicing variants (v1 and v2) and their deletion mutants lacking C­terminal regions into MiaPaCa pancreatic cancer cells. The results demonstrated that both splicing variants showed nuclear translocation regardless of the C­terminal deletions, suggesting the role of the N­terminal regions. Given that SRP9 is an RNA­binding protein, the study of RNA immunoprecipitation revealed that signaling pathways involved in cancer progression and protein translation were downregulated in nuclear­translocated v1 and v2. Undoubtedly, further studies of the nuclear translocation of SRP9 will open an avenue to optimize the precise evaluation and therapeutic control of pancreatic cancer.