KCNK1 promotes proliferation and metastasis of breast cancer cells by activating lactate dehydrogenase A (LDHA) and up-regulating H3K18 lactylation.

Breast cancer is the most prevalent malignancy and the most significant contributor to mortality in female oncology patients. Potassium Two Pore Domain Channel Subfamily K Member 1 (KCNK1) is differentially expressed in a variety of tumors, but the mechanism of its function in breast cancer is unknown. In this study, we found for the first time that KCNK1 was significantly up-regulated in human breast cancer and was correlated with poor prognosis in breast cancer patients. KCNK1 promoted breast cancer proliferation, invasion, and metastasis in vitro and vivo. Further studies unexpectedly revealed that KCNK1 increased the glycolysis and lactate production in breast cancer cells by binding to and activating lactate dehydrogenase A (LDHA), which promoted histones lysine lactylation to induce the expression of a series of downstream genes and LDHA itself. Notably, increased expression of LDHA served as a vicious positive feedback to reduce tumor cell stiffness and adhesion, which eventually resulted in the proliferation, invasion, and metastasis of breast cancer. In conclusion, our results suggest that KCNK1 may serve as a potential breast cancer biomarker, and deeper insight into the cancer-promoting mechanism of KCNK1 may uncover a novel therapeutic target for breast cancer treatment.

Splicing factor derived circular RNA circCAMSAP1 accelerates nasopharyngeal carcinoma tumorigenesis via a SERPINH1/c-Myc positive feedback loop.

BACKGROUND: Circular RNAs play an important role in tumor genesis and progression, but they have not been sufficiently studied in patients with nasopharyngeal carcinoma (NPC). METHODS: The circular RNA, circCAMSAP1, was screened in NPC cells by RNA sequencing analysis. The expression of circCAMSAP1 in NPC tissues was examined by real-time quantitative polymerase chain reaction (RT-qPCR) and in situ hybridization. Wound-healing, transwell, MTT and flow cytometry assays, and nude mouse tumor models were used to explore the effect of circCAMSAP1 on proliferation and metastasis of NPC in vitro or in vivo. The downstream proteins regulated by circCAMSAP1 were screened using mass spectrometry. The interaction between circCAMSAP1 and the SERPINH1 mRNA was identified using the circular RNA immunoprecipitation method and the luciferase reporter assay. The interaction between SERPINH1 and transcription factor c-Myc was verified through Co-immunoprecipitation (Co-IP) and immunofluorescence. The effect of c-Myc on the generation of circCAMSAP1 was examined through RT-qPCR and chromatin immunoprecipitation. Finally, the splicing factors that promote the production of circCAMSAP1 were explored by RT-qPCR and RNA immunoprecipitation (RIP). RESULTS: We found that circCAMSAP1 was highly expressed in NPC tissues and promoted NPC proliferation and metastasis. Additionally, circCAMSAP1 promoted SERPINH1 expression through improved SERPINH1 mRNA stability by binding to the 3'-untranslated region (3'UTR) of SERPINH1. Highly expressed SERPINH1 reduced the ubiquitination-degradation rate of c-Myc, causing increased tumorigenesis. Meanwhile, c-Myc, cooperating with splicing factor 10 (SRSF10), could also promote CAMSAP1 pre-mRNA transcription and back-splicing, forming a positive feedback of circCAMSAP1 production, resulting in the proliferation and metastasis of NPC. CONCLUSIONS: Our findings revealed that circCAMSAP1 promotes NPC proliferation and metastasis by binding to the 3'UTR of SERPINH1, suggesting that the positive feedback of circCAMSAP1-SERPINH1-c-Myc may serve as a prognostic biomarker or therapeutic target in patients with NPC.

Circular RNA circPVT1 promotes nasopharyngeal carcinoma metastasis via the ß-TrCP/c-Myc/SRSF1 positive feedback loop.

BACKGROUND: Circular RNAs (circRNAs) act as gene expression regulators and are involved in cancer progression. However, their functions have not been sufficiently investigated in nasopharyngeal carcinoma (NPC). METHODS: The expression profiles of circRNAs in NPC cells within different metastatic potential were reanalyzed. Quantitative reverse transcription PCR and in situ hybridization were used to detect the expression level of circPVT1 in NPC cells and tissue samples. The association of expression level of circPVT1 with clinical properties of NPC patients was evaluated. Then, the effects of circPVT1 expression on NPC metastasis were investigated by in vitro and in vivo functional experiments. RNA immunoprecipitation, pull-down assay and western blotting were performed to confirm the interaction between circPVT1 and ß-TrCP in NPC cells. Co-immunoprecipitation and western blotting were performed to confirm the interaction between ß-TrCP and c-Myc in NPC cells. RESULTS: We find that circPVT1, a circular RNA, is significantly upregulated in NPC cells and tissue specimens. In vitro and in vivo experiments showed that circPVT1 promotes the invasion and metastasis of NPC cells. Mechanistically, circPVT1 inhibits proteasomal degradation of c-Myc by binding to ß-TrCP, an E3 ubiquiting ligase. Stablization of c-Myc by circPVT1 alters the cytoskeleton remodeling and cell adhesion in NPC, which ultimately promotes the invasion and metastasis of NPC cells. Furthermore, c-Myc transcriptionally upregulates the expression of SRSF1, an RNA splicing factor, and recruits SRSF1 to enhance the biosynthesis of circPVT1 through coupling transcription with splicing, which forms a positive feedback for circPVT1 production. CONCLUSIONS: Our results revealed the important role of circPVT1 in the progression of NPC through the ß-TrCP/c-Myc/SRSF1 positive feedback loop, and circPVT1 may serve as a prognostic biomarker or therapeutic target in patients with NPC.

Circular RNA circRNF13 inhibits proliferation and metastasis of nasopharyngeal carcinoma via SUMO2.

BACKGROUND: Circular RNAs (circRNAs) are widely expressed in human cells and are closely associated with cancer development. However, they have rarely been investigated in the context of nasopharyngeal carcinoma (NPC). METHODS: We screened a new circRNA, circRNF13, in NPC cells using next-generation sequencing of mRNA. Reverse transcription polymerase chain reaction and RNA fluorescence in situ hybridization were used to detect circRNF13 expression in 12 non-tumor nasopharyngeal epithelial (NPE) tissues and 36 NPC samples. Cell proliferation was detected using MTT and flow cytometry assays, and colony formation capability was detected using colony formation assays. Cell migration and invasion were analyzed using wound-healing and Transwell assays, respectively. Cell glycolysis was analyzed using the Seahorse glycolytic stress test. Glucose transporter type 1 (GLUT1) ubiquitination and SUMOylation modifications were analyzed using co-immunoprecipitation and western blotting. CircRNF13 and Small Ubiquitin-like Modifier 2 (SUMO2) interactions were analyzed using RNA pull-down and luciferase reporter assays. Finally, to test whether circRNF13 inhibited NPC proliferation and metastasis in vivo, we used a xenograft nude mouse model generated by means of subcutaneous or tail vein injection. RESULTS: We found that circRNF13 was stably expressed at low levels in NPC clinical tissues and NPC cells. In vitro and in vivo experiments showed that circRNF13 inhibited NPC proliferation and metastasis. Moreover, circRNF13 activated the SUMO2 protein by binding to the 3'- Untranslated Region (3'-UTR) of the SUMO2 gene and prolonging the half-life of SUMO2 mRNA. Upregulation of SUMO2 promotes GLUT1 degradation through SUMOylation and ubiquitination of GLUT1, which regulates the AMPK-mTOR pathway by inhibiting glycolysis, ultimately resulting in the proliferation and metastasis of NPC. CONCLUSIONS: Our results revealed that a novel circRNF13 plays an important role in the development of NPC through the circRNF13-SUMO2-GLUT1 axis. This study implies that circRNF13 mediates glycolysis in NPC by binding to SUMO2 and provides an important theoretical basis for further elucidating the pathogenesis of NPC and targeted therapy.

Recent advances of fluorescent biosensors based on cyclic signal amplification technology in biomedical detection.

The cyclic signal amplification technology has been widely applied for the ultrasensitive detection of many important biomolecules, such as nucleic acids, proteins, enzymes, adenosine triphosphate (ATP), metal ions, exosome, etc. Due to their low content in the complex biological samples, traditional detection methods are insufficient to satisfy the requirements for monitoring those biomolecules. Therefore, effective and sensitive biosensors based on cyclic signal amplification technology are of great significance for the quick and simple diagnosis and treatment of diseases. Fluorescent biosensor based on cyclic signal amplification technology has become a research hotspot due to its simple operation, low cost, short time, high sensitivity and high specificity. This paper introduces several cyclic amplification methods, such as rolling circle amplification (RCA), strand displacement reactions (SDR) and enzyme-assisted amplification (EAA), and summarizes the research progress of using this technology in the detection of different biomolecules in recent years, in order to provide help for the research of more efficient and sensitive detection methods.

Long noncoding RNAs involvement in Epstein-Barr virus infection and tumorigenesis.

The Epstein-Barr virus (EBV) is a ubiquitous γ-herpesvirus related to various types of cancers, including epithelial nasopharyngeal carcinoma, gastric carcinoma, and lymphoma. Long noncoding RNAs (lncRNAs) are expressed extensively in mammalian cells and play crucial roles in regulating various cellular processes and multiple cancers. Cellular lncRNAs can be differentially expressed induced by EBV infection. The dysregulated lncRNAs probably modulate the host immune response and other biological functions. At present, lncRNAs have been found to be significantly increased or decreased in EBV-infected cells, exosomes and EBV-associated cancers, suggesting their potential function and clinical application as biomarkers. In addition, EBV-encoded lncRNAs, BART and BHLF1 lncRNAs, may play roles in the viral oncogenesis. Analysis of the specific lncRNAs involved in interactions with the EBV machinery will provide information on their potential mechanism of action during multiple steps of EBV tumorigenesis. Here, we review the current knowledge regarding EBV-related lncRNAs and their possible roles in the pathogenesis of EBV-associated cancers.

The role of exosomal noncoding RNAs in cancer.

Extracellular vesicles (EVs) membranes enclose nanosized vesicles with a size range of 30-150 nm and are plentiful in our body in both physiological and pathological conditions. Exosomes, a type of EV, are important mediators of intracellular communication among tumor cells, immune cells, and stromal cells. They can shuttle bioactive molecules, such as proteins, lipids, RNA, and DNA; however, the precise function of EVs remains largely unknown. In recent years, tumor-associated cargo in exosomes has been a hot topic in research, especially with respect to noncoding RNAs (ncRNAs). Herein, we review the role of exosomal ncRNAs, including miRNAs and long noncoding RNAs, in tumor biological processes. Clinically, exosomal ncRNAs may eventually become novel biomarkers and therapeutic targets in cancer progression.

Advances and prospects of mRNA vaccines in cancer immunotherapy.

Cancer vaccines, designed to activate the body's own immune system to fight against tumors, are a current trend in cancer treatment and receiving increasing attention. Cancer vaccines mainly include oncolytic virus vaccine, cell vaccine, peptide vaccine and nucleic acid vaccine. Over the course of decades of research, oncolytic virus vaccine T-VEC, cellular vaccine sipuleucel-T, various peptide vaccines, and DNA vaccine against HPV positive cervical cancer have brought encouraging results for cancer therapy, but are losing momentum in development due to their respective shortcomings. In contrast, the advantages of mRNA vaccines such as high safety, ease of production, and unmatched efficacy are on full display. In addition, advances in technology such as pseudouridine modification have cracked down the bottleneck for developing mRNA vaccines including instability, innate immunogenicity, and low efficiency of in vivo delivery. Several cancer mRNA vaccines have achieved promising results in clinical trials, and their usage in conjunction with other immune checkpoint inhibitors (ICIs) has further boosted the efficiency of anti-tumor immune response. We expect a rapid development of mRNA vaccines for cancer immunotherapy in the near future. This review provides a brief overview of the current status of mRNA vaccines, highlights the action mechanism of cancer mRNA vaccines, their recent advances in clinical trials, and prospects for their clinical applications.

NK cells as powerful therapeutic tool in cancer immunotherapy.

BACKGROUND: Natural killer (NK) cells have gained considerable attention and hold great potential for their application in tumor immunotherapy. This is mainly due to their MHC-unrestricted and pan-specific recognition capabilities, as well as their ability to rapidly respond to and eliminate target cells. To artificially generate therapeutic NK cells, various materials can be utilized, such as peripheral blood mononuclear cells (PBMCs), umbilical cord blood (UCB), induced pluripotent stem cells (iPSCs), and NK cell lines. Exploiting the therapeutic potential of NK cells to treat tumors through in vivo and in vitro therapeutic modalities has yielded positive therapeutic results. CONCLUSION: This review provides a comprehensive description of NK cell therapeutic approaches for tumors and discusses the current problems associated with these therapeutic approaches and the prospects of NK cell therapy for tumors.

CircCDYL2 bolsters radiotherapy resistance in nasopharyngeal carcinoma by promoting RAD51 translation initiation for enhanced homologous recombination repair.

BACKGROUND: Radiation therapy stands to be one of the primary approaches in the clinical treatment of malignant tumors. Nasopharyngeal Carcinoma, a malignancy predominantly treated with radiation therapy, provides an invaluable model for investigating the mechanisms underlying radiation therapy resistance in cancer. While some reports have suggested the involvement of circRNAs in modulating resistance to radiation therapy, the underpinning mechanisms remain unclear. METHODS: RT-qPCR and in situ hybridization were used to detect the expression level of circCDYL2 in nasopharyngeal carcinoma tissue samples. The effect of circCDYL2 on radiotherapy resistance in nasopharyngeal carcinoma was demonstrated by in vitro and in vivo functional experiments. The HR-GFP reporter assay determined that circCDYL2 affected homologous recombination repair. RNA pull down, RIP, western blotting, IF, and polysome profiling assays were used to verify that circCDYL2 promoted the translation of RAD51 by binding to EIF3D protein. RESULTS: We have identified circCDYL2 as highly expressed in nasopharyngeal carcinoma tissues, and it was closely associated with poor prognosis. In vitro and in vivo experiments demonstrate that circCDYL2 plays a pivotal role in promoting radiotherapy resistance in nasopharyngeal carcinoma. Our investigation unveils a specific mechanism by which circCDYL2, acting as a scaffold molecule, recruits eukaryotic translation initiation factor 3 subunit D protein (EIF3D) to the 5'-UTR of RAD51 mRNA, a crucial component of the DNA damage repair pathway to facilitate the initiation of RAD51 translation and enhance homologous recombination repair capability, and ultimately leads to radiotherapy resistance in nasopharyngeal carcinoma. CONCLUSIONS: These findings establish a novel role of the circCDYL2/EIF3D/RAD51 axis in nasopharyngeal carcinoma radiotherapy resistance. Our work not only sheds light on the underlying molecular mechanism but also highlights the potential of circCDYL2 as a therapeutic sensitization target and a promising prognostic molecular marker for nasopharyngeal carcinoma.

Spatial Transcriptomic and Metabolomic Landscapes of Oral Submucous Fibrosis-Derived Oral Squamous Cell Carcinoma and its Tumor Microenvironment.

In South and Southeast Asia, the habit of chewing betel nuts is prevalent, which leads to oral submucous fibrosis (OSF). OSF is a well-established precancerous lesion, and a portion of OSF cases eventually progress to oral squamous cell carcinoma (OSCC). However, the specific molecular mechanisms underlying the malignant transformation of OSCC from OSF are poorly understood. In this study, the leading-edge techniques of Spatial Transcriptomics (ST) and Spatial Metabolomics (SM) are integrated to obtain spatial location information of cancer cells, fibroblasts, and immune cells, as well as the transcriptomic and metabolomic landscapes in OSF-derived OSCC tissues. This work reveals for the first time that some OSF-derived OSCC cells undergo partial epithelial-mesenchymal transition (pEMT) within the in situ carcinoma (ISC) region, eventually acquiring fibroblast-like phenotypes and participating in collagen deposition. Complex interactions among epithelial cells, fibroblasts, and immune cells in the tumor microenvironment are demonstrated. Most importantly, significant metabolic reprogramming in OSF-derived OSCC, including abnormal polyamine metabolism, potentially playing a pivotal role in promoting tumorigenesis and immune evasion is discovered. The ST and SM data in this study shed new light on deciphering the mechanisms of OSF-derived OSCC. The work also offers invaluable clues for the prevention and treatment of OSCC.

Epstein-Barr virus downregulates microRNA 203 through the oncoprotein latent membrane protein 1: a contribution to increased tumor incidence in epithelial cells.

The Epstein-Barr virus (EBV) is highly associated with nasopharyngeal carcinoma (NPC), and it regulates some microRNAs (miRNAs) that are involved in the development of cancer. The role of EBV in the deregulation of cellular miRNAs and how this affects the progression of NPC remain to be investigated. An analysis of the miRNA profile in an EBV-infected cell line revealed that miRNA 203 (miR-203) was downregulated. miR-203 is expressed specifically in epithelial cells. This downregulation of miR-203 was further verified and functionally analyzed. miR-203 was downregulated substantially in epithelial cells and NPC tissues that were latently infected with EBV. Downregulation of miR-203 also occurred during the early stage of EBV infection. Furthermore, the viral oncoprotein, latent membrane protein 1 (LMP1), was responsible for downregulation of miR-203. Removal of the latent EBV genome or suppression of LMP1 resulted in restoration of miR-203 expression. EBV-LMP1 mediated the downregulation of miR-203 at the primary transcript level. E2F3 and CCNG1 were identified as target genes of miR-203. Ectopic expression of miR-203 inhibited EBV-induced S-phase entry and transformation in vivo. Overexpression of the targets overcame the effects of miR-203 mimics on the cell cycle, and the expression of target genes in tumor models was inhibited by miR-203. Inhibitors of Jun N-terminal protein kinase (JNK) and NF-κB blocked miR-203 downregulation. These results imply that EBV promotes malignancy by downregulating cellular miR-203, which contributes to the etiology of NPC.

Microsatellite Status Detection of Colorectal Cancer: Evaluation of Inconsistency between PCR and IHC.

Objective: An essential component of precision medical treatment for colorectal cancer (CRC) is the use of microsatellite state in combination with polymerase chain reaction (PCR) and immunohistochemistry (IHC) as the primary clinical detection methods. Microsatellite instability-high (MSI-H) or mismatch-repair deficiency (dMMR) accounts for about 15% of all CRC patients. Characterized by a high mutation burden, MSI-H is a predictive biomarker of immune checkpoint inhibitors (ICIs). Misdiagnosis of microsatellite status has been shown to be an important cause of resistance to immune checkpoint inhibitors. Therefore, a rapid and accurate assessment of microsatellite status can be beneficial for precision medicine in CRC. Methods: We evaluated the rate of discordance between PCR and IHC detection of microsatellite status from a cohort of patients that had 855 colorectal cancers. PCR-based microsatellite assay was performed using a set of five monomorphic mononucleotide makers (NR-24, BAT-25, CAT-25, BAT-26, MONO-27) and two polymorphic pentanucleotide (Penta D and Penta E). IHC was used to detect the absence of mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2). The inconsistency rates of the two assays were evaluated. Results: Among 855 patients,15.6% (134 to 855) cases were identified as MSI-H by PCR, whereas 16.9% (145 to 855) cases were identified as dMMR by IHC. There were 45 patients with discordant results between IHC and PCR. Of these, 17 patients were classified as MSI-H/pMMR and 28 patients as MSS/dMMR. When the clinicopathological characteristics of these 45 patients were compared to those of the 855 patients, it was found that more patients were younger than 65 years old (80% to 63%), more were male (73% to 62%), more were located in the right colon (49% to 32%), and more were poorly differentiated (20% to 15%). Conclusion: Our study demonstrated a high concordance between the PCR and IHC results. In order to reduce the ineffective treatment of ICIs due to MSI misdiagnosis, the patient's age, gender, tumor location and degree of differentiation should be included in the clinician's selection of MSI testing in colorectal cancer.

Overview and countermeasures of cancer burden in China.

Cancer is one of the leading causes of human death worldwide. Treatment of cancer exhausts significant medical resources, and the morbidity and mortality caused by cancer is a huge social burden. Cancer has therefore become a serious economic and social problem shared globally. As an increasingly prevalent disease in China, cancer is a huge challenge for the country's healthcare system. Based on recent data published in the Journal of the National Cancer Center on cancer incidence and mortality in China in 2016, we analyzed the current trends in cancer incidence and changes in cancer mortality and survival rate in China. And also, we examined several key risk factors for cancer pathogenesis and discussed potential countermeasures for cancer prevention and treatment in China.

Emerging roles of tRNA in cancer.

Transfer RNAs (tRNAs) play pivotal roles in the transmission of genetic information, and abnormality of tRNAs directly leads to translation disorders and causes diseases, including cancer. The complex modifications enable tRNA to execute its delicate biological function. Alteration of appropriate modifications may affect the stability of tRNA, impair its ability to carry amino acids, and disrupt the pairing between anticodons and codons. Studies confirmed that dysregulation of tRNA modifications plays an important role in carcinogenesis. Furthermore, when the stability of tRNA is impaired, tRNAs are cleaved into small tRNA fragments (tRFs) by specific RNases. Though tRFs have been found to play vital regulatory roles in tumorigenesis, its formation process is far from clear. Understanding improper tRNA modifications and abnormal formation of tRFs in cancer is conducive to uncovering the role of metabolic process of tRNA under pathological conditions, which may open up new avenues for cancer prevention and treatment.

Application prospect of circular RNA-based neoantigen vaccine in tumor immunotherapy.

Neoantigen is a protein produced by mutant gene, which is only expressed in tumor cells. It is an ideal target for therapeutic tumor vaccines. Although synthetic long peptide (SLP)-based neoantigen vaccine, DNA-based neoantigen vaccine, and mRNA-based neoantigen vaccine are all in the development stage, they have some inherent shortcomings. Therefore, researchers turned their attention to a new type of "non-coding RNA (ncRNA)", circular RNA (circRNA), for potential better choice. Because of its unique high stability and protein-coding capacity, circRNA is a promising target in the field of neoantigen vaccine. In this paper, we reviewed the feasibility of circRNA encoding neoantigens, summarized the construction process, explained the mechanism of circRNA vaccine in vitro, and discussed the advantages and disadvantages of circRNA vaccine and possible combination with other immunotherapies.

Circular RNA circRILPL1 promotes nasopharyngeal carcinoma malignant progression by activating the Hippo-YAP signaling pathway.

Circular RNAs (circRNAs) play an important regulatory role in the pathogenesis and progression of nasopharyngeal carcinoma (NPC), which have not been thoroughly elucidated. In this study, we revealed for the first time that circRILPL1 was upregulated in NPC, weakened adhesion and decreased stiffness of NPC cells, and promoted NPC proliferation and metastasis in vitro and in vivo. Mechanistically, circRILPL1 inhibited the LATS1-YAP kinase cascade by binding to and activating ROCK1, resulting in decrease of YAP phosphorylation. Binding and cooperating with transport receptor IPO7, circRILPL1 promoted the translocation of YAP from the cytoplasm to the nucleus, where YAP enhanced the transcription of cytoskeleton remodeling genes CAPN2 and PXN. By which, circRILPL1 contributed to the pathogenesis of NPC. Our results demonstrated that circRILPL1 promoted the proliferation and metastasis of NPC through activating the Hippo-YAP signaling pathway by binding to both ROCK1 and IPO7. Highly expressed circRILPL1 in NPC may serve as an important biomarker for tumor diagnosis and may also be a potential therapeutic target.

Cyclophilin A binds to AKT1 and facilitates the tumorigenicity of Epstein-Barr virus by mediating the activation of AKT/mTOR/NF-κB positive feedback loop.

The AKT/mTOR and NF-κB signalings are crucial pathways activated in cancers including nasopharyngeal carcinoma (NPC), which is prevalent in southern China and closely related to Epstein-Barr virus (EBV) infection. How these master pathways are persistently activated in EBV-associated NPC remains to be investigated. Here we demonstrated that EBV-encoded latent membrane protein 1 (LMP1) promoted cyclophilin A (CYPA) expression through the activation of NF-κB. The depletion of CYPA suppressed cell proliferation and facilitated apoptosis. CYPA was able to bind to AKT1, thus activating AKT/mTOR/NF-κB signaling cascade. Moreover, the use of mTOR inhibitor, rapamycin, subverted the activation of the positive feedback loop, NF-κB/CYPA/AKT/mTOR. It is reasonable that LMP1 expression derived from initial viral infection is enough to assure the constant potentiation of AKT/mTOR and NF-κB signalings. This may partly explain the fact that EBV serves as a tumor-promoting factor with minimal expression of the viral oncoprotein LMP1 in malignancies. Our findings provide new insight into the understanding of causative role of EBV in tumorigenicity during latent infection.

Potential applications of N6 -methyladenosine modification in the prognosis and treatment of cancers via modulating apoptosis, autophagy, and ferroptosis.

N6 -methyladenosine (m6 A) is one of the most abundant modifications determining the fate of RNA. Currently, m6 A modification is tightly connected with tumorigenesis and presents novel promise in clinical applications. Regulated cell death (RCD) is a programmed mechanism that plays a complicated role in malignant transition. Regarding the main forms of RCD, aberrant levels of m6 A modification have been detected during the progression of apoptosis, autophagy, ferroptosis, necroptosis, and pyroptosis in several diseases. However, few reviews have elucidated the correlation between m6 A-modified RCD and carcinogenesis. In this review, we summarize the regulators of m6 A methylation and their functions in carcinogenesis through an overview of m6 A-modified RCD. Additionally, we assume the potential role of m6 A modification regulators as novel biomarkers for chemotherapies and precision medicine. Furthermore, we review the controversies and conflicts in m6 A explorations and predict future orientations of m6 A-modified RCD for clinical applications. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs.

A fluorescence strategy for circRNA quantification in tumor cells based on T7 nuclease-assisted cycling enzymatic amplification.

Circular Ribonucleic Acid (CircRNA) plays regulatory roles in many biological processes, such as tumors and metabolic diseases. Due to the fact that circRNA is more stable and conservative than linear RNA, circRNA has become a potential biomarker in early clinical diagnosis and biomedical research. Therefore, the quantification of circRNA expression level is of importance for understanding their functions and their applications for disease diagnosis and treatment. Nevertheless, due to the low abundance of circRNA, it is still a challenge for the analysis of circRNA in cells. Herein, we proposed a sensitive detection method for circRNA based on the T7 exonuclease-assisted cycling enzymatic amplification. The fluorescent sensor was constructed by a hairpin molecular beacon and T7 exonuclease. With the cycling enzymatic amplification process, this sensor achieved the limit of detection of 1 pM with a good linear correlation in the range of 0-100 pM (R2 = 0.9891) using circBART2.2 as a model. Furthermore, we applied the proposed method in the determination of circBART2.2 in cell lysates. The results demonstrated that this method has promising applications in early diagnosis of Epstein-Barr virus (EBV) infection-related diseases using circRNA as the biomarker.