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1.
Int Immunopharmacol ; 134: 112197, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38733826

RESUMO

BACKGROUND: In China, CRC incidence is escalating. The main hurdles are heterogeneity and drug resistance. This research delves into cellular senescence in CRC, aiming to devise a prognostic model and pinpoint mechanisms impacting drug resistance. METHODS: Mendelian randomization (MR) analysis confirmed the association between CRC and cellular aging. The Cancer Genome Atlas (TCGA)-CRC data served as the training set, with GSE38832 and GSE39582 as validation sets. Various bioinformatics methods were employed to construct and validate a risk model. CRC cells with NADPH Oxidase 4 (NOX4) knockout were generated using CRISPR-Cas9 technology. Protein blotting and colony formation assays elucidated the role of NOX4 in CRC cell aging and drug resistance. RESULTS: A prognostic model, derived from dataset analysis, uncovered a link between high-risk groups and cancer progression. Notable differences in the tumor microenvironment were observed between risk groups. Finally, NOX4 was found to be linked with aging and drug resistance in CRC. CONCLUSION: This research presents a novel senescence-based CRC prognosis model. It identifies NOX4's role in CRC drug resistance, suggesting it is a potential treatment target.


Assuntos
Senescência Celular , Neoplasias Colorretais , Resistencia a Medicamentos Antineoplásicos , NADPH Oxidase 4 , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , NADPH Oxidase 4/metabolismo , NADPH Oxidase 4/genética , Prognóstico , Microambiente Tumoral , Linhagem Celular Tumoral , Masculino , Feminino
2.
Cell Signal ; 118: 111134, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38484942

RESUMO

Colorectal cancer (CRC) is one of the most common malignant tumors with complex molecular regulatory mechanisms. Alternative splicing (AS), a fundamental regulatory process of gene expression, plays an important role in the occurrence and development of CRC. This study analyzed AS Percent Spliced In (PSI) values from 49 pairs of CRC and normal samples in the TCGA SpliceSeq database. Using Lasso and SVM, AS features that can differentiate colorectal cancer from normal were screened. Univariate COX regression analysis identified prognosis-related AS events. A risk model was constructed and validated using machine learning, Kaplan-Meier analysis, and Decision Curve Analysis. The regulatory effect of protein arginine methyltransferase 5 (PRMT5) on poly(RC) binding protein 1 (PCBP1) was verified by immunoprecipitation experiments, and the effect of PCBP1 on the AS of Obscurin (OBSCN) was verified by PCR. Five AS events, including HNF4A.59461.AP and HNF4A.59462.AP, were identified, which can distinguish CRC from normal tissue. A machine learning model using 21 key AS events accurately predicted CRC prognosis. High-risk patients had significantly shorter survival times. PRMT5 was found to regulate PCBP1 function and then influence OBSCN AS, which may drive CRC progression. The study concluded that some AS events is significantly different in CRC and normal tissues, and some of these AS events are related to the prognosis of CRC. In addition, PRMT family-driven arginine modifications play an important role in CRC-specific AS events.


Assuntos
Processamento Alternativo , Neoplasias Colorretais , Humanos , Processamento Alternativo/genética , Arginina , Estimativa de Kaplan-Meier , Metiltransferases , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Proteína-Arginina N-Metiltransferases/genética
3.
Aging (Albany NY) ; 15(12): 5734-5750, 2023 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-37348024

RESUMO

Mounting evidence demonstrates that long noncoding RNAs (lncRNAs) have critical roles in the initiation and progression of cancer. Here, we report that small nucleolar RNA host gene 3 (SNHG3) is a key regulator of breast cancer progression. We analyzed RNA sequencing data to explore abnormally expressed lncRNAs in breast cancer. The effects of SNHG3 on breast cancer were investigated via in vitro and in vivo assays (CCK-8 assay, colony formation assay, flow cytometry assay, EdU assay, xenograft model, immunohistochemistry, and Western blot). The mechanism of SNHG3 action was explored through bioinformatics, RNA fluorescence in situ hybridization, luciferase reporter assay, RNA pull-down assay, chromatin immunoprecipitation assay and RNA immunoprecipitation assay. We found that SNHG3 expression was upregulated in breast cancer tissues and that its high expression level was associated with poor survival. We also found that high SNHG3 expression was partly induced by STAT3. Moreover, SNHG3 knockdown significantly repressed breast cancer cell growth both in vitro and in vivo. In the cytoplasm, SNHG3 facilitated the expression of Casein kinase II-A1 (CSNK2A1) by absorbing miR-485-5p and recruiting the HuR protein, participating in the malignant progression of breast cancer. Taken together, our study reveals a SNHG3-based regulatory network, which plays an oncogenic role in breast cancer and suggests that SNHG3 may serve as a potential target for the diagnosis and treatment of breast cancer.


Assuntos
Neoplasias da Mama , MicroRNAs , RNA Longo não Codificante , Humanos , Feminino , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias da Mama/genética , Caseína Quinase II/genética , Caseína Quinase II/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Hibridização in Situ Fluorescente , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Proliferação de Células/genética
4.
ACS Appl Mater Interfaces ; 13(23): 27548-27556, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34060813

RESUMO

Continuous developments of innovative anticounterfeiting strategies are vital to restrain the fast-growing counterfeit markets. Physical unclonable function (PUF)-based taggants allow for a practical solution to provide irreproducible codes for strong authentication. Herein, an advanced anticounterfeiting strategy with multiple security levels was successfully developed using screen printing and atomic layer infiltration (ALI) techniques. Macroscale poly(dimethylsiloxane) (PDMS) patterns were fabricated for primary verification. Spontaneous formation of random wrinkles with size in the micrometer scale was achieved on the top surface of screen-printed PDMS patterns due to the anisotropic relief and redistribution of extra compressive stress after Al2O3 infiltration, which can be used for senior authentication by image identification using the artificial intelligence (AI) technique. Furthermore, the complexity and security level of a code, which are proportional to the minutia density, can be adjusted by the morphology of the wrinkles in terms of amplitude and wavelength via the degree of Al2O3 permeation depending on ALI conditions. These spontaneously formed random wrinkles were demonstrated for validation and decoding with AI, exhibiting the merits of being unclonable, nondestructive, universally adaptable, environmentally stable, and mass-producible, and sufficiently adaptable for an industry-suitable authentication strategy.

5.
ACS Appl Mater Interfaces ; 13(13): 15701-15708, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33764737

RESUMO

Optical security labels play a significant role in protecting both our wealth and health. However, simultaneously meeting the requirements including low-cost fabrication, easy detection, and high-level security is still challenging for security labels. Here, we design an unclonable anti-counterfeiting system with triple-level security by using the inkjet printing technique, which can be authenticated by naked eyes, a portable microscope, and a fluorescence microscope. These labels are achieved by printing microscale quantum dot (QD) ink droplets on premodified substrates with random-distributed glass microspheres. Due to the unique capillary action induced by the glass microspheres, QDs in the ink droplets are deposited around the microspheres, forming microscale multicircular patterns. Multiple pinning of QDs at the three-phase contact lines appears during the evaporation of the droplet, resulting in the formation of a nanoscale labyrinthine pattern around the microspheres. The nanoscale labyrinth pattern and the microscale multicircular microsphere array, together with the printed macroscopic image, constitute a triple-level progressive anti-counterfeiting system. Moreover, the system is compatible with an artificial intelligence-based identification strategy that allows rapid identification and verification of the unclonable security labels.

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