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1.
BMC Genomics ; 25(1): 659, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956500

ABSTRACT

BACKGROUND: Neither a TYRP1-mediated highly conserved genetic network underlying skin color towards optimum defense nor the pathological tendency of its mutation is well understood. The Oujiang Color Common Carp (Cyprinus carpio var. color) as a model organism, offering valuable insights into genetics, coloration, aquaculture practices, and environmental health. Here, we performed a comparative skin transcriptome analysis on TYRP1 mutant and wild fishes by applying a conservative categorical approach considering different color phenotypes. RESULTS: Our results reveal that an unusual color phenotype may be sensitized with TYRP1 mutation as a result of upregulating several genes related to an anti-inflammatory autoimmune system in response to the COMT-mediated catecholamine neurotransmitters in the skin. Particularly, catecholamines-derived red/brown, red with blue colored membrane attack complex, and brown/grey colored reduced eumelanin are expected to be aggregated in the regenerated cells. CONCLUSIONS: It is, thus, concluded that the regenerated cells with catecholamines, membrane attack complex, and eumelanin altogether may contribute to the formation of the unusual (coffee-like) color phenotype in TYRP1 mutant.


Subject(s)
Carps , Gene Regulatory Networks , Mutation , Skin Pigmentation , Animals , Carps/genetics , Skin Pigmentation/genetics , Phenotype , Fish Proteins/genetics , Fish Proteins/metabolism , Gene Expression Profiling , Transcriptome
2.
PLoS Biol ; 22(6): e3002666, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38905316

ABSTRACT

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.


Subject(s)
Breast Neoplasms , Cell Proliferation , Histones , Humans , Breast Neoplasms/pathology , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Female , Cell Proliferation/genetics , Animals , Cell Line, Tumor , Histones/metabolism , Mice , Gene Expression Regulation, Neoplastic , Up-Regulation/genetics , Neoplasm Metastasis , Potassium Channels, Tandem Pore Domain/metabolism , Potassium Channels, Tandem Pore Domain/genetics , Lactate Dehydrogenase 5/metabolism , Lactate Dehydrogenase 5/genetics , Mice, Nude , Neoplasm Invasiveness , Glycolysis/genetics , L-Lactate Dehydrogenase/metabolism , L-Lactate Dehydrogenase/genetics , Mice, Inbred BALB C , Prognosis , Cell Movement/genetics
3.
Biochem Pharmacol ; 224: 116204, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38615920

ABSTRACT

Calcium/calmodulin-dependent protein kinase IV (CaMK4) is a versatile serine/threonine kinase involved in various cellular functions. It regulates T-cell differentiation, podocyte function, tumor cell proliferation/apoptosis, ß cell mass, and insulin sensitivity. However, the underlying molecular mechanisms are complex and remain incompletely understood. The aims of this review are to highlight the latest advances in the regulatory mechanisms of CaMK4 underlying T-cell imbalance and parenchymal cell mass in multiple diseases. The structural motifs and activation of CaMK4, as well as the potential role of CaMK4 as a novel therapeutic target are also discussed.


Subject(s)
Calcium-Calmodulin-Dependent Protein Kinase Type 4 , Humans , Calcium-Calmodulin-Dependent Protein Kinase Type 4/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Type 4/antagonists & inhibitors , Animals
4.
J Exp Clin Cancer Res ; 43(1): 122, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38654320

ABSTRACT

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.


Subject(s)
Nasopharyngeal Carcinoma , Rad51 Recombinase , Radiation Tolerance , Recombinational DNA Repair , Humans , Nasopharyngeal Carcinoma/radiotherapy , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Carcinoma/metabolism , Nasopharyngeal Carcinoma/pathology , Rad51 Recombinase/metabolism , Rad51 Recombinase/genetics , Mice , Animals , Radiation Tolerance/genetics , RNA, Circular/genetics , Nasopharyngeal Neoplasms/radiotherapy , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/metabolism , Nasopharyngeal Neoplasms/pathology , Cell Line, Tumor , Female , Male , Prognosis , Mice, Nude
5.
Article in English | MEDLINE | ID: mdl-38538872

ABSTRACT

Acupuncture was studied to investigate the mechanism of its effect on protease vitality and free radical damage in Type I CIA rats induced by type II collagen. The study divided rats into a control group (injected with physiological saline, n = 10), a model group (injected with type II collagen, n = 10), and an intervention group (injected with type II collagen + acupuncture ST36 and GB39, 3 times a week, for a total of 4 weeks, n = 10) based on the different injected drugs. Then, various indicators of the mice were experimentally tested using joint index scoring, H&E histological staining, protein blotting, and immunohistochemistry staining methods. Acupuncture ST36 and GB39 can reduce arthritis scores, histological staining scores, and increase MVD in CIA rats. And reduce protease levels, alleviate inflammation, synovial hyperplasia, and angiogenesis. In addition, the intervention group TNF-α, IL-1ß and IL-6 mRNA were reduced, and the clearance rates of hydrogen peroxide free radicals and nitric oxide free radicals were increased. The expression levels of ROS and MDA decrease, while the expression levels of SOD increase It has been proved that acupuncture at ST36 and GB39 can inhibit the release of ROS, reduce protease activity, inflammation, synovial hyperplasia, angiogenesis and free radical damage, thus reducing the severity of CIA (Collagen-Induced Arthritis) in rats.

6.
Front Cardiovasc Med ; 11: 1286271, 2024.
Article in English | MEDLINE | ID: mdl-38347952

ABSTRACT

Background: Due to its potential to significantly reduce scanning time while delivering accurate results for cardiac volume function, compressed sensing (CS) has gained traction in cardiovascular magnetic resonance (CMR) cine. However, further investigation is necessary to explore its feasibility and impact on myocardial strain results. Materials and methods: A total of 102 participants [75 men, 46.5 ± 17.1 (SD) years] were included in this study. Each patient underwent four consecutive cine sequences with the same slice localization, including the reference multi-breath-hold balanced steady-state free precession (bSSFPref) cine, the CS cine with the same flip angle as bSSFPref before (CS45) and after (eCS45) contrast enhancement, and the CS cine (eCS70) with a 70-degree flip angle after contrast enhancement. Biventricular strain parameters were derived from cine images. Two-tailed paired t-tests were used for data analysis. Results: Global radial strain (GRS), global circumferential strain (GCS), and global longitudinal strain (GLS) were observed to be significantly lower in comparison to those obtained from bSSFPref sequences for both the right and left ventricles (all p < 0.001). No significant difference was observed on biventricular GRS-LAX (long-axis) and GLS values derived from enhanced and unenhanced CS cine sequences with the same flip angle, but remarkable reductions were noted in GRS-SAX (short-axis) and GCS values (p < 0.001). After contrast injection, a larger flip angle caused a significant elevation in left ventricular strain results (p < 0.001) but did not affect the right ventricle. The increase in flip angle appeared to compensate for contrast agent affection on left ventricular GRS-SAX, GCS values, and right ventricular GRS-LAX, GLS values. Conclusion: Despite incorporating gadolinium contrast agents and applying larger flip angles, single breath-hold CS cine sequences consistently yielded diminished strain values for both ventricles when compared with conventional cine sequences. Prior to employing this single breath-hold CS cine sequence to refine the clinical CMR examination procedure, it is crucial to consider its impact on myocardial strain results.

7.
J Clin Med ; 13(3)2024 Jan 28.
Article in English | MEDLINE | ID: mdl-38337447

ABSTRACT

BACKGROUND: Although compressed sensing (CS) accelerated cine holds immense potential to replace conventional cardiovascular magnetic resonance (CMR) cine, how to use CS-based cine appropriately during clinical CMR examinations still needs exploring. METHODS: A total of 104 patients (46.5 ± 17.1 years) participated in this prospective study. For each participant, a balanced steady state free precession (bSSFP) cine was acquired as a reference, followed by two CS accelerated cine sequences with identical parameters before and after contrast injection. Lastly, a CS accelerated cine sequence with an increased flip angle was obtained. We subsequently compared scanning time, image quality, and biventricular function parameters between these sequences. RESULTS: All CS cine sequences demonstrated significantly shorter acquisition times compared to bSSFPref cine (p < 0.001). The bSSFPref cine showed higher left ventricular ejection fraction (LVEF) than all CS cine sequences (all p < 0.001), but no significant differences in LVEF were observed among the three CS cine sequences. Additionally, CS cine sequences displayed superior global image quality (p < 0.05) and fewer artifacts than bSSFPref cine (p < 0.005). Unenhanced CS cine and enhanced CS cine with increased flip angle showed higher global image quality than other cine sequences (p < 0.005). CONCLUSION: Single breath-hold CS cine delivers precise biventricular function parameters and offers a range of benefits including shorter scan time, better global image quality, and diminished motion artifacts. This innovative approach holds great promise in replacing conventional bSSFP cine and optimizing the CMR examination workflow.

8.
Cell Oncol (Dordr) ; 47(3): 733-757, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38170381

ABSTRACT

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.


Subject(s)
Immunotherapy , Killer Cells, Natural , Neoplasms , Humans , Killer Cells, Natural/immunology , Neoplasms/therapy , Neoplasms/immunology , Immunotherapy/methods , Animals
9.
Adv Sci (Weinh) ; 11(12): e2306515, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38229179

ABSTRACT

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.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Oral Submucous Fibrosis , Humans , Oral Submucous Fibrosis/genetics , Oral Submucous Fibrosis/metabolism , Oral Submucous Fibrosis/pathology , Carcinoma, Squamous Cell/genetics , Squamous Cell Carcinoma of Head and Neck , Transcriptome , Tumor Microenvironment , Cell Transformation, Neoplastic , Gene Expression Profiling
10.
ACS Nano ; 17(23): 24055-24069, 2023 Dec 12.
Article in English | MEDLINE | ID: mdl-38044579

ABSTRACT

Hydrogels have attracted tremendous attention as favorable corneal substitutes for treating severe infectious keratitis (IK). However, current hydrogel-based corneal substitutes were majorly designed to promote the single stage of corneal regeneration, which falls short in meeting the clinical management needs of severe IK including the multiple phases of corneal wound healing. Herein, we introduce a versatile hybrid hydrogel (SQPV) composed of silk fibroin and chitosan, which exhibits spatiotemporal properties for drug release. The SQPV is fabricated by incorporating verteporfin-loaded poly(lactic-co-glycolic)-polyethylene glycol-o-nitrobenzene micelles into a hydrogel network, which is formed from methacrylate silk fibroin and glycidyl methacrylate functionalized quaternized chitosan containing polydeoxyribonucleotide. This double network approach results in a material with exceptional anti-inflammatory, antibacterial, and proliferative stimulation and tissue remodeling regulation capabilities. Furthermore, SQPV showcases mechanical strength and transparency akin to those of native cornea. Extensive in vitro and in vivo studies validate SQPV's ability to effectively eliminate residual bacteria, mitigate inflammation, foster regeneration of corneal epithelium and stroma, prevent corneal scarring, and ultimately expedite wound healing. In summary, the SF/CS-based hybrid hydrogel may represent a promising substitute for comprehensive corneal repair and regeneration in severe IK.


Subject(s)
Chitosan , Fibroins , Keratitis , Humans , Hydrogels/pharmacology , Chitosan/pharmacology , Drug Liberation , Wound Healing , Keratitis/drug therapy , Anti-Bacterial Agents/pharmacology
11.
Medicine (Baltimore) ; 102(42): e35268, 2023 Oct 20.
Article in English | MEDLINE | ID: mdl-37861541

ABSTRACT

A member of the short-chain dehydrogenase/reductase superfamily (DHRS1, SDR19C1) is a member of the short-chain dehydrogenase/reductase superfamily and a potential predictor of hepatocellular carcinoma (HCC). However, the role of DHRS1 in HCC immunity remains unclear. We systematically analyzed the association between DHRS1 and HCC immunity with transcriptional and clinical data from the Tumor Immune Estimation Resource, an integrated repository portal for tumor immune system interactions, and cBioPortal databases. Six DHRS1-associated immunomodulators strongly correlated with survival and were uncovered by exploiting univariate and multivariate Cox analyses. We created a risk score for each patient by adding the points from each immunomodulator and then classified them into high and low risk categories. Survival analysis were used to compare the overall survival between the 2 groups, and the receiver operating characteristic curve was applied to assess the accuracy of the risk score. Data from our center were adopted as the external validation set, the risk score was calculated using the risk coefficient of the 6 genes in the training cohort, and survival analysis were executed to verify the experimental group results. A nomogram was ultimately constructed with the R package. Our data revealed a correlation between the levels of immune cell infiltration and either the DHRS1 gene copy numbers or mRNA levels in HCC. Second, we generated a signature based on the 6 DHRS1-related immunomodulators (KDR, TNFRSF4, CD276, TNFSF4, SLAMF6, and SIGLEC9). We postulate that the generated risk scores would serve as an independent indicator of HCC prognosis, with an area under the receiver operating characteristic curve for the risk score of 0.743. We further established external validation sets to reconfirm the predictive validity of the risk score. Finally, a prognostic nomogram and calibration curve were created. The DHRS1 gene may exert an impact on HCC immunity. We posit that the nominated immune signature based on DHRS1-associated immunomodulators could constitute a promising prognostic biomarker in HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/genetics , Prognosis , Liver Neoplasms/genetics , Adjuvants, Immunologic , Computational Biology , Oxidoreductases , OX40 Ligand , B7 Antigens
12.
Front Plant Sci ; 14: 1274392, 2023.
Article in English | MEDLINE | ID: mdl-37900737

ABSTRACT

Identifying loci for root system architecture (RSA) traits and developing available markers are crucial for wheat breeding. In this study, RSA-related traits, including total root length (TRL), total root area (TRA), and number of root tips (NRT), were evaluated in the Doumai/Shi4185 recombinant inbred line (RIL) population under hydroponics. In addition, both the RILs and parents were genotyped using the wheat 90K single-nucleotide polymorphism (SNP) array. In total, two quantitative trait loci (QTLs) each for TRL (QTRL.caas-4A.1 and QTRL.caas-4A.2), TRA (QTRA.caas-4A and QTRA.caas-4D), and NRT (QNRT.caas-5B and QNRT.caas-5D) were identified and each explaining 5.94%-9.47%, 6.85%-7.10%, and 5.91%-10.16% phenotypic variances, respectively. Among these, QTRL.caas-4A.1 and QTRA.caas-4A overlapped with previous reports, while QTRL.caas-4A.2, QTRA.caas-4D, QNRT.caas-5B, and QNRT.caas-5D were novel. The favorable alleles of QTRL.caas-4A.1, QTRA.caas-4A, and QTRA.caas-5B were contributed by Doumai, whereas the favorable alleles of QTRL.caas-4A.2, QTRA.caas-4D, and QTRA.caas-5D originated from Shi 4185. Additionally, two competitive allele-specific PCR (KASP) markers, Kasp_4A_RL (QTRA.caas-4A) and Kasp_5D_RT (QNRT.caas-5D), were developed and validated in 165 wheat accessions. This study provides new loci and available KASP markers, accelerating wheat breeding for higher yields.

13.
Acta Pharm Sin B ; 13(10): 4234-4252, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37799387

ABSTRACT

The mesencephalic astrocyte-derived neurotrophic factor (MANF) has been recently identified as a neurotrophic factor, but its role in hepatic fibrosis is unknown. Here, we found that MANF was upregulated in the fibrotic liver tissues of the patients with chronic liver diseases and of mice treated with CCl4. MANF deficiency in either hepatocytes or hepatic mono-macrophages, particularly in hepatic mono-macrophages, clearly exacerbated hepatic fibrosis. Myeloid-specific MANF knockout increased the population of hepatic Ly6Chigh macrophages and promoted HSCs activation. Furthermore, MANF-sufficient macrophages (from WT mice) transfusion ameliorated CCl4-induced hepatic fibrosis in myeloid cells-specific MANF knockout (MKO) mice. Mechanistically, MANF interacted with S100A8 to competitively block S100A8/A9 heterodimer formation and inhibited S100A8/A9-mediated TLR4-NF-κB signal activation. Pharmacologically, systemic administration of recombinant human MANF significantly alleviated CCl4-induced hepatic fibrosis in both WT and hepatocytes-specific MANF knockout (HKO) mice. This study reveals a mechanism by which MANF targets S100A8/A9-TLR4 as a "brake" on the upstream of NF-κB pathway, which exerts an impact on macrophage differentiation and shed light on hepatic fibrosis treatment.

14.
Cancer Lett ; 573: 216381, 2023 10 01.
Article in English | MEDLINE | ID: mdl-37660884

ABSTRACT

In recent years, there have been multiple breakthroughs in cancer immunotherapy, with immune checkpoint inhibitors becoming the most promising treatment strategy. However, available drugs are not always effective. As an emerging immune checkpoint molecule, CD155 has become an important target for immunotherapy. This review describes the structure and function of CD155, its receptors TIGIT, CD96, and CD226, and summarizes that CD155 expressed by tumor cells can upregulate its expression through the DNA damage response pathway and Ras-Raf-MEK-ERK signaling pathway. This review also elaborates the mechanism of immune escape after binding CD155 to its receptors TIGIT, CD96, and CD226, and summarizes the current progress of immunotherapy research regarding CD155 and its receptors. Besides, it also discusses the future direction of checkpoint immunotherapy.


Subject(s)
Immunotherapy , Neoplasms , Humans , Neoplasms/therapy , Immune Checkpoint Inhibitors , MAP Kinase Signaling System , Antigens, CD
15.
Adv Sci (Weinh) ; 10(30): e2302558, 2023 10.
Article in English | MEDLINE | ID: mdl-37632718

ABSTRACT

Single cell RNA sequencing (scRNA-seq) provides a great convenience for studying tumor occurrence and development for its ability to study gene expression at the individual cell level. However, patient-derived tumor tissues are composed of multiple types of cells including tumor cells and adjacent non-malignant cells such as stromal cells and immune cells. The spatial locations of various cells in situ tissues plays a pivotal role in the occurrence and development of tumors, which cannot be elucidated by scRNA-seq alone. Spatially resolved transcriptomics (SRT) technology emerges timely to explore the unrecognized relationship between the spatial background of a particular cell and its functions, and is increasingly used in cancer research. This review provides a systematic overview of the SRT technologies that are developed, in particular the more widely used cutting-edge SRT technologies based on next-generation sequencing (NGS). In addition, the main achievements by SRT technologies in precisely unveiling the underappreciated spatial locations on gene expression and cell function with unprecedented high-resolution in cancer research are emphasized, with the aim of developing more effective clinical therapeutics oriented to a deeper understanding of the interaction between tumor cells and surrounding non-malignant cells.


Subject(s)
Neoplasms , Transcriptome , Humans , Transcriptome/genetics , Gene Expression Profiling , High-Throughput Nucleotide Sequencing , Technology , Neoplasms/genetics
16.
Cell Death Differ ; 30(7): 1679-1694, 2023 07.
Article in English | MEDLINE | ID: mdl-37173390

ABSTRACT

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.


Subject(s)
Nasopharyngeal Neoplasms , RNA, Circular , Humans , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Carcinoma/metabolism , RNA, Circular/genetics , Transcription Factors/genetics , Transcription Factors/metabolism , Cell Proliferation , Cell Line, Tumor , Hippo Signaling Pathway , Nasopharyngeal Neoplasms/metabolism , Gene Expression Regulation, Neoplastic , rho-Associated Kinases/genetics
17.
Br J Cancer ; 129(2): 204-221, 2023 08.
Article in English | MEDLINE | ID: mdl-37095185

ABSTRACT

Currently, more than 170 modifications have been identified on RNA. Among these RNA modifications, various methylations account for two-thirds of total cases and exist on almost all RNAs. Roles of RNA modifications in cancer are garnering increasing interest. The research on m6A RNA methylation in cancer is in full swing at present. However, there are still many other popular RNA modifications involved in the regulation of gene expression post-transcriptionally besides m6A RNA methylation. In this review, we focus on several important RNA modifications including m1A, m5C, m7G, 2'-O-Me, Ψ and A-to-I editing in cancer, which will provide a new perspective on tumourigenesis by peeking into the complex regulatory network of epigenetic RNA modifications, transcript processing, and protein translation.


Subject(s)
Neoplasms , RNA Processing, Post-Transcriptional , Humans , RNA, Messenger/metabolism , RNA/genetics , RNA/metabolism , Neoplasms/genetics , Methylation
18.
Adv Healthc Mater ; 12(21): e2300192, 2023 08.
Article in English | MEDLINE | ID: mdl-37097884

ABSTRACT

The repair of large-diameter corneal stroma defects is a major clinical problem. Although some studies have attempted to use hydrogels to repair corneal damage, most of these hydrogels can only be used for focal stromal defects that are ≤3.5 mm in diameter due to poor hydrogel adhesion. Here, a photocurable adhesive hydrogel that mimics the extracellular matrix (ECM) with regard to composition for repairing 6 mm-diameter corneal stromal defects in rabbits is investigated. This ECM-like adhesive can be rapidly cured after light exposure, with high light transmittance and good mechanical properties. More importantly, this hydrogel maintains the viability and adhesion of cornea-derived cells and promotes their migration in vitro in 2D and 3D culture environments. Proteomics analysis confirms that the hydrogel promotes cell proliferation and ECM synthesis. Furthermore, in rabbit corneal stromal defect repair experiments, it is proven by histological and proteomic analysis that this hydrogel can effectively promote corneal stroma repair, reduce scar formation, and increase corneal stromal-neural regeneration at the six months follow-up. This work demonstrates the great application of ECM-like adhesive hydrogels for the regeneration of large-diameter corneal defects.


Subject(s)
Corneal Stroma , Regeneration , Animals , Rabbits , Adhesives , Hydrogels/pharmacology , Proteomics , Extracellular Matrix , Nerve Regeneration
19.
Cancer Lett ; 563: 216170, 2023 06 01.
Article in English | MEDLINE | ID: mdl-37054943

ABSTRACT

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.


Subject(s)
Neoplasms , RNA, Transfer , Humans , RNA, Transfer/genetics , RNA, Transfer/metabolism , Anticodon , Amino Acids , Neoplasms/genetics
20.
Cancer Lett ; 563: 216190, 2023 06 01.
Article in English | MEDLINE | ID: mdl-37062328

ABSTRACT

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.


Subject(s)
Cancer Vaccines , Neoplasms , Vaccines, DNA , Humans , Antigens, Neoplasm , RNA, Circular/genetics , Neoplasms/therapy , Neoplasms/drug therapy , Cancer Vaccines/genetics , Cancer Vaccines/therapeutic use , Immunotherapy/methods
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