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Self-supervised monocular depth estimation can exhibit excellent performance in static environments due to the multi-view consistency assumption during the training process. However, it is hard to maintain depth consistency in dynamic scenes when considering the occlusion problem caused by moving objects. For this reason, we propose a method of self-supervised self-distillation for monocular depth estimation (SS-MDE) in dynamic scenes, where a deep network with a multi-scale decoder and a lightweight pose network are designed to predict depth in a self-supervised manner via the disparity, motion information, and the association between two adjacent frames in the image sequence. Meanwhile, in order to improve the depth estimation accuracy of static areas, the pseudo-depth images generated by the LeReS network are used to provide the pseudo-supervision information, enhancing the effect of depth refinement in static areas. Furthermore, a forgetting factor is leveraged to alleviate the dependency on the pseudo-supervision. In addition, a teacher model is introduced to generate depth prior information, and a multi-view mask filter module is designed to implement feature extraction and noise filtering. This can enable the student model to better learn the deep structure of dynamic scenes, enhancing the generalization and robustness of the entire model in a self-distillation manner. Finally, on four public data datasets, the performance of the proposed SS-MDE method outperformed several state-of-the-art monocular depth estimation techniques, achieving an accuracy (δ1) of 89% while minimizing the error (AbsRel) by 0.102 in NYU-Depth V2 and achieving an accuracy (δ1) of 87% while minimizing the error (AbsRel) by 0.111 in KITTI.
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BACKGROUND: Colorectal cancer (CRC) is one of the cancers with high morbidity and mortality worldwide. Chemotherapy is commonly used for metastatic or more advanced CRC. The mechanism of CRC chemoresistance is still under active investigation. Therefore, we identify and validate differentially expressed genes (DEGs) between oxaliplatin/5-FU resistant and sensitive CRC cells. METHODS AND RESULTS: Three datasets of colorectal cancer patients (GSE28691, GSE81006, and GSE77932) from the Gene Expression Omnibus (GEO) database were analyzed and volcano plots for DEGs were generated using the GEO2R tool. The intersection of three GEO datasets showed that GABRP was significantly upregulated in chemo-resistant CRC cells or patients with an adjusted p-value less than 0.01. The potential protein-protein interaction (PPI) network with GABRP was analyzed by the Search Tool for the Retrieval of Interaction Gene/Proteins (STRING) website. The PPI network predicted ANKRD66, CLINT1, HAP1, PLCL1, GABARPAP, GABARAPL1, NSF, GABARAPL2, TRAK2, and CLIC3 had a high likelihood to interact with GABRP. Especially, GABARAP, GABARAPL1, ANKRD66, CLINT1, and CLIC3 were enriched as the most possibly associated proteins with GABRP among the networks. GABRP was significantly more expressed in both oxaliplatin/5-FU resistant CRC cells than in those counterpart sensitive CRC cells using quantitative PCR (qPCR) analysis. Consistently, TCGA, Oncomine, and Human Protein Atlas (HPA) databases confirmed that higher expression of GABRP was robustly found in CRC patients than those in other various cancer types or normal colon tissues. CONCLUSION: We identify GABRP as a promising drug target to mediate oxaliplatin or 5-FU resistance in CRC. It provided the theoretical basis and potential clinical value for CRC patients.
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Neoplasias Colorrectales , Resistencia a Antineoplásicos , Humanos , Oxaliplatino/farmacología , Resistencia a Antineoplásicos/genética , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Proteínas/genética , Fluorouracilo/farmacología , Fluorouracilo/uso terapéutico , Regulación Neoplásica de la Expresión GénicaRESUMEN
BACKGROUND: Long noncoding RNAs (lncRNAs) have driven research focused on their effects as oncogenes or tumor suppressors involved in carcinogenesis. However, the functions and mechanisms of most lncRNAs in colorectal cancer (CRC) remain unclear. METHODS: The expression of DLGAP1-AS2 was assessed by quantitative RT-PCR in multiple CRC cohorts. The impacts of DLGAP1-AS2 on CRC growth and metastasis were evaluated by a series of in vitro and in vivo assays. Furthermore, the underlying mechanism of DLGAP1-AS2 in CRC was revealed by RNA pull down, RNA immunoprecipitation, RNA sequencing, luciferase assays, chromatin immunoprecipitation, and rescue experiments. RESULTS: We discovered that DLGAP1-AS2 promoted CRC tumorigenesis and metastasis by physically interacting with Elongin A (ELOA) and inhibiting its protein stability by promoting tripartite motif containing 21 (Trim21)-mediated ubiquitination modification and degradation of ELOA. In particular, we revealed that DLGAP1-AS2 decreases phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) expression by inhibiting ELOA-mediated transcriptional activating of LHPP and thus blocking LHPP-dependent suppression of the AKT signaling pathway. In addition, we also demonstrated that DLGAP1-AS2 was bound and stabilized by cleavage and polyadenylation specificity factor (CPSF2) and cleavage stimulation factor (CSTF3). CONCLUSIONS: The discovery of DLGAP1-AS2, a promising prognostic biomarker, reveals a new dimension into the molecular pathogenesis of CRC and provides a prospective treatment target for this disease.
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Neoplasias Colorrectales , MicroARNs , ARN Largo no Codificante , Humanos , Carcinogénesis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Transformación Celular Neoplásica/genética , Factor de Especificidad de Desdoblamiento y Poliadenilación/genética , Factor de Especificidad de Desdoblamiento y Poliadenilación/metabolismo , Neoplasias Colorrectales/patología , Elonguina/genética , Elonguina/metabolismo , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismoRESUMEN
Fusobacterium nucleatum infection plays vital roles in colorectal cancer (CRC) progression. Overexpression of microRNA-4717-3p (miR-4717) was reported to be upregulated in F. nucleatum positive CRC tissues, however, the underlying mechanism is unknown. In this study, we found that miR-4717 promoted CRC cell proliferation in vitro and growth of CRC in vivo following F. nucleatum infection. MicroRNA-4717 suppressed the expression of mitogen-activated protein kinase kinase 4 (MAP2K4), a tumor suppressor, by directly targeting its 3'-UTR. Furthermore, we confirmed that methyltransferase-like 3 (METTL3)-dependent m6 A methylation could methylate primary (pri)-miR-4717, which further promoted the maturation of pri-miR-4717, and METTL3 positively regulated CRC cell proliferation through miR-4717/MAP2K4 pathways. In conclusion, F. nucleatum-induced miR-4717 excessive maturation through METTL3-dependent m6 A modification promotes CRC cell proliferation, which provides a potential therapeutic target and diagnostic biomarker for CRC.
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Neoplasias Colorrectales , MicroARNs , Humanos , Fusobacterium nucleatum/genética , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Colorrectales/patología , Proliferación Celular/genética , Regiones no Traducidas 3' , Metiltransferasas/genéticaRESUMEN
This publisher's note corrects an affiliation error in Opt. Lett.41, 4118 (2016)OPLEDP0146-959210.1364/OL.41.004118.
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As a potential tumor suppressor, the detailed clinical application value of sorting nexin 1 (SNX1) has not been elucidated in colorectal cancer (CRC). The aim of the present study was to evaluate the expression of SNX1 in CRC tissues and to determine its correlation with clinicopathologic characteristics and its impact on patient's prognosis. We detected the expression of SNX1 mRNA in 72 CRC patients and SNX1 protein in 237 CRC patients by real-time polymerase chain reaction (RT-PCR) and immunohistochemical staining, respectively. Relationship between the expression of SNX1 and various clinicopathological features in these patients was evaluated. Both the mRNA and protein expression of SNX1 were remarkably decreased in CRC tissues compared with paired non-cancerous tissues, and the down-regulation of SNX1 protein was strongly associated with poor differentiation and poor overall survival (OS) rate of CRC patients. Ectopic SNX1 expression repressed CRC cell growth and promoted tumor sensitivity to most commonly used chemotherapeutic drugs (oxaliplatin and 5-Fluorouracil). In conclusion, overexpression of SNX1 may serve as a new therapeutic strategy for CRC.
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Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica , Nexinas de Clasificación/genética , Adulto , Anciano , Antineoplásicos/farmacología , Biomarcadores de Tumor , Línea Celular Tumoral , Proliferación Celular , Neoplasias Colorrectales/patología , Regulación hacia Abajo , Femenino , Fluorouracilo/farmacología , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Carga TumoralRESUMEN
A trace-gas sensor, based on quartz-enhanced photoacoustic spectroscopy (QEPAS), consisting of two acoustically coupled micro-resonators (mR) with an off-axis 20 kHz quartz tuning fork (QTF) is demonstrated. The complete acoustically coupled mR system is optimized based on finite-element simulations and is experimentally verified. The QEPAS sensor is pumped resonantly by a nanosecond pulsed single-mode mid-infrared optical parametric oscillator. The sensor is used for spectroscopic measurements on methane in the 3.1-3.5 µm wavelength region with a resolution bandwidth of 1 cm-1 and a detection limit of 0.8 ppm. An Allan deviation analysis shows that the detection limit at the optimum integration time for the QEPAS sensor is 32 ppbv at 190 s, and that the background noise is due solely to the thermal noise of the QTF.
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Tumor-associated macrophages (TAMs) play a key role in inducing an immunosuppressive tumor microenvironment (TME) and cancer immune escape. We previously revealed that PDL1 (a key immune checkpoint) was upregulated in TAMs and induced M2 polarization, highlighting PDL1 in TAMs as a promising cancer therapeutic target. In this study, we developed an engineered milk exosome (mExo) system decorated with M2pep (an M2 macrophage binding peptide) and 7D12 (an anti-EGFR nanobody) (7D12-mExo-M2pep-siPDL1) to specifically deliver siPDL1 into M2 TAMs. A series of in vitro and in vivo assays showed that the dually targeted engineered mExos efficiently delivered siPDL1 into M2 TAMs and repolarized them into M1 macrophages, restoring CD8+ T cell immune activity and remodeling TME. Importantly, systemically administered 7D12-mExo-M2pep-siPDL1 showed efficient single-agent antitumor activity, resulting in nearly 90% tumor growth inhibition in a mouse model of orthotopic epidermal growth factor receptor (EGFR) cancer. Collectively, our study indicates that PDL1 is a promising target for TAM-based cancer immunotherapy, and our engineered mExo-based nanomedicine represents a novel tool for specifically targeting M2 TAMs, distinguishing this novel therapeutic method from other TAM-targeting therapies and highlighting its promising clinical potential.
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Exosomas , Neoplasias , Animales , Ratones , Macrófagos Asociados a Tumores , Leche , Macrófagos , Neoplasias/terapia , Microambiente TumoralRESUMEN
Colorectal cancer (CRC) ranks as the third most prevalent cancer type globally. Nevertheless, the fundamental mechanisms driving CRC progression remain ambiguous, and the prognosis for the majority of patients diagnosed at an advanced stage is dismal. YWHA/14-3-3 proteins serve as central nodes in several signaling pathways and are closely related to tumorigenesis and progression. However, their exact roles in CRC are still poorly elucidated. In this study, we revealed that YWHAG was the most significantly upregulated member of the YWHA/14-3-3 family in CRC tissues and was associated with a poor prognosis. Subsequent phenotypic experiments showed that YWHAG promoted the proliferation, migration, and invasion of CRC cells. Mechanistically, RNA-seq data showed that multiple signaling pathways, including Wnt and epithelial-mesenchymal transition, were potentially regulated by YWHAG. CTTN was identified as a YWHAG-associated protein, and mediated its tumor-promoting functions by activating the Wnt/ß-catenin signaling in CRC cells. In summary, our data indicate that YWHAG facilitates the proliferation, migration, and invasion of CRC cells by modulating the CTTN-Wnt/ß-catenin signaling pathway, which offers a novel perspective for the treatment of CRC.
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Neoplasias Colorrectales , beta Catenina , Humanos , beta Catenina/metabolismo , Vía de Señalización Wnt , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Pronóstico , Carcinogénesis , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Movimiento Celular , Transición Epitelial-Mesenquimal , Cortactina/metabolismo , Proteínas 14-3-3/metabolismoRESUMEN
BACKGROUND: Elongin A (ELOA), our previous work revealed, serves as a novel tumor suppressor in colorectal cancer. However, the function and mechanism of ELOA in other cancer types, including gastric cancer (GC), remain to be elucidated. METHODS: The expression of ELOA was measured by quantitative reverse transcription-polymerase chain reaction and western blot. The effects of ELOA on GC growth and metastasis were assessed through a series of in-vitro and in-vivo assays. Furthermore, the potential mechanism of ELOA was revealed by RNA sequencing, dual luciferase reporter assay, chromatin immunoprecipitation, and rescue experiments in GC. RESULTS: We uncovered increased expression of ELOA in GC tissues compared with paired normal tissues via bioinformatic analyses and our sample detection. Enhanced ELOA expression in GC tissues was obviously correlated with poor tumor differentiation, lymph node metastasis, advanced tumor stage, and a poor prognosis. A series of functional experiments showed that ELOA promoted the proliferation and metastasis of GC. Mechanistically, we revealed that the decreased levels of miR-490-3p caused the upregulation of ELOA in GC. Both RNA-seq and ChIP assays revealed that ELOA transcriptionally activated retinol-binding protein 1 (RBP1) by binding to its promotor. Furthermore, specific knockdown of RBP1 reduced the tumor-promoting ability of ELOA in GC cells. CONCLUSIONS: In summary, our findings demonstrate that ELOA exerts oncogenic properties by activating RBP1 expression, providing the basis for a promising therapeutic target in GC.
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Small extracellular vesicles (sEVs) have shown excellent prospects as drug delivery systems for cancer therapy. However, the inherent non-targeting and short blood circulation characteristics severely restrict their practical applications as a delivery system. In addition, post-encapsulating drugs into sEVs also remains challenging. Here, we constructed an engineered cell line that secreted multifunctional sEVs (termed NBsEV204) with 7D12 (an anti-EGFR nanobody) and hCD47 decorations on their surface, as well as high levels of miR-204-5p encapsulation. NBsEV204 exhibited extended blood circulation and improved macrophage-mediated phagocytosis of tumor cells by blocking CD47 signaling. Importantly, NBsEV204 specifically targeted EGFR+ tumor cells and showed robust tumor-suppressive effects both in vitro and in vivo. Overall, this study provides a convenient and feasible method to produce off-the-shelf anticancer sEV nanomedicine, which exhibits tremendous potential for clinical translation.
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Vesículas Extracelulares , MicroARNs , Nanomedicina , Anticuerpos , Transporte Biológico , Línea CelularRESUMEN
Shiga toxin type 2 (Stx2) is the primary virulence factor produced by Shiga toxin-producing enterohemorrhagic Escherichia coli (STEC), which causes epidemic outbreaks of gastrointestinal sickness and potentially fatal sequela hemolytic uremic syndrome (HUS). Most studies on Stx2-induced apoptosis have been performed with holotoxins, but the mechanism of how the A and B subunits of Stx2 cause apoptosis in cells is not clear. Here, we found that Stx2 A-subunit (Stx2A) induced mitochondrial damage, PINK1/Parkin-dependent mitophagy and apoptosis in Caco-2 cells. PINK1/Parkin-dependent mitophagy caused by Stx2A reduced apoptosis by decreasing the accumulation of reactive oxidative species (ROS). Mechanistically, Stx2A interacts with Tom20 on mitochondria to initiate the translocation of Bax to mitochondria, leading to mitochondrial damage and apoptosis. Overall, these data suggested that Stx2A induces mitochondrial damage, mitophagy and apoptosis via the interaction of Tom20 in Caco-2 cells and that mitophagy caused by Stx2A ameliorates apoptosis by eliminating damaged mitochondria. These findings provide evidence for the potential use of Tom20 inhibition as an anti-Shiga toxin therapy.
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Ammonia production via glutamate dehydrogenase is inhibited by SIRT4, a sirtuin that displays both amidase and non-amidase activities. The processes underlying the regulation of ammonia removal by amino acids remain unclear. Here, we report that SIRT4 acts as a decarbamylase that responds to amino acid sufficiency and regulates ammonia removal. Amino acids promote lysine 307 carbamylation (OTCCP-K307) of ornithine transcarbamylase (OTC), which activates OTC and the urea cycle. Proteomic and interactome screening identified OTC as a substrate of SIRT4. SIRT4 decarbamylates OTCCP-K307 and inactivates OTC in an NAD+-dependent manner. SIRT4 expression was transcriptionally upregulated by the amino acid insufficiency-activated GCN2-eIF2α-ATF4 axis. SIRT4 knockout in cultured cells caused higher OTCCP-K307 levels, activated OTC, elevated urea cycle intermediates and urea production via amino acid catabolism. Sirt4 ablation decreased male mouse blood ammonia levels and ameliorated CCl4-induced hepatic encephalopathy phenotypes. We reveal that SIRT4 safeguards cellular ammonia toxicity during amino acid catabolism.
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Aminoácidos , Amoníaco , Animales , Masculino , Ratones , Células Cultivadas , Proteómica , Urea/metabolismoRESUMEN
Persistent Fusobacterium nucleatum infection is associated with the development of human colorectal cancer (CRC) and promotes tumorigenicity, but the underlying mechanisms remain unclear. Here, we reported that F. nucleatum promoted the tumorigenicity of CRC, which was associated with F. nucleatum-induced microRNA-31 (miR-31) expression in CRC tissues and cells. F. nucleatum infection inhibited autophagic flux by miR-31 through inhibiting syntaxin-12 (STX12) and was associated with the increased intracellular survival of F. nucleatum. Overexpression of miR-31 in CRC cells promoted their tumorigenicity by targeting eukaryotic initiation factor 4F-binding protein 1/2 (eIF4EBP1/2), whereas miR-31 knockout mice were resistant to the formation of colorectal tumors. In conclusion, F. nucleatum, miR-31, and STX12 form a closed loop in the autophagy pathway, and continuous F. nucleatum-induced miR-31 expression promotes the tumorigenicity of CRC cells by targeting eIF4EBP1/2. These findings reveal miR-31 as a potential diagnostic biomarker and therapeutic target in CRC patients with F. nucleatum infection.
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Both Fusobacterium nucleatum (F. nucleatum) and long non-coding RNA (lncRNA) EVADR are associated with colorectal cancer (CRC), but their relationship with CRC metastasis and the mechanisms by which EVADR promotes CRC metastasis are poorly understood. Here, we report that F. nucleatum promotes colorectal cancer cell metastasis to the liver and lung and that it can be detected in CRC-metastasis colonization in mouse models. Furthermore, F. nucleatum upregulates the expression of EVADR, which can increase the metastatic ability of CRC cells in vivo and in vitro. Mechanistically, elevated EVADR serves as a modular scaffold for the Y-box binding protein 1 (YBX1) to directly enhance the translation of epithelial-mesenchymal transition (EMT)-related factors, such as Snail, Slug, and Zeb1. These findings suggest that EVADR induced by F. nucleatum promotes colorectal cancer metastasis through YBX1-dependent translation. The EVADR-YBX1 axis may be useful for the prevention and treatment of patients with F. nucleatum-associated CRC metastasis.
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Neoplasias Colorrectales , Infecciones por Fusobacterium , ARN Largo no Codificante , Animales , Carcinogénesis/genética , Neoplasias Colorrectales/patología , Infecciones por Fusobacterium/complicaciones , Infecciones por Fusobacterium/microbiología , Infecciones por Fusobacterium/patología , Fusobacterium nucleatum/genética , Ratones , ARN Largo no Codificante/genéticaRESUMEN
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. As the main GIST drivers, gain-of-function mutations in KIT or PDGFRA are closely associated with not only tumor development and progression but also therapeutic response. In addition to the status of KIT and PDGFRA, little is known about other potential GIST-related genes. In this study, we identified the mutation profiles in 49 KIT-mutated GIST tumors using the whole exome sequencing (WES) method. Furthermore, some representative mutations were further validated in an independent GIST cohort using the SNaPshot SNP assay. We identified extensive and diverse mutations of KIT in GIST, including many undescribed variants. In addition, we revealed some new tumor-related gene mutations with unknown pathogenicity. By enrichment analyses of gene function and protein-protein interaction network construction, we showed that these genes were enriched in several important cancer- or metabolism-related signaling pathways, including PI3K-AKT,RTK-RAS, Notch, Wnt, Hippo, mTOR, AMPK, and insulin signaling. In particular, DNA repair-related genes, including MLH1, MSH6, BRCA1, BRCA2, and POLE, are frequently mutated in GISTs, suggesting that immune checkpoint blockade may have promising clinical applications for these GIST subpopulations. In conclusion, in addition to extensive and diverse mutations of KIT, some genes related to DNA-repair and cell metabolism may play important roles in the development, progression and therapeutic response of GIST.
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Development of novel mid-infrared (MIR) lasers could ultimately boost emerging detection technologies towards innovative spectroscopic and imaging solutions. Photoacoustic (PA) modality has been heralded for years as one of the most powerful detection tools enabling high signal-to-noise ratio analysis. Here, we demonstrate a novel, compact and sensitive MIR-PA system for carbon dioxide (CO2) monitoring at its strongest absorption band by combining a gas-filled fiber laser and PA technology. Specifically, the PA signals were excited by a custom-made hydrogen (H2) based MIR Raman fiber laser source with a pulse energy of â 18 µJ, quantum efficiency of â 80% and peak power of â 3.9 kW. A CO2 detection limit of 605 ppbv was attained from the Allan deviation. This work constitutes an alternative method for advanced high-sensitivity gas detection.
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BACKGROUND: The emergence and prevalence of plasmid-mediated colistin-resistant bacterial strains in recent years have raised great concerns in clinical medicine. It is urgently needed to develop a cheaper, faster, simpler, sensitive, and specific molecular detection method to identify and monitor the dissemination of the transferable resistant determinants. METHODS AND RESULTS: Herein, eight pairs of primers were designed to set up a multiplex PCR method for the rapid and efficient determination of reported mcr genes. This assay can give results within 85 min (35 min for amplification and 50 min for electrophoresis). We validated the feasibility of this assay by testing the presence of mcr genes in 60 colistin-resistant isolates. CONCLUSION: Our multiplex PCR technique exhibits remarkable advantages in the light of clear identification, efficiency of amplification, as well as the time consuming for detection, and thus could be useful for the surveillance and epidemiological research of plasmid-mediated colistin resistance, particularly for the under-resourced laboratories.
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OBJECTIVE: A colistin-resistant Escherichia coli strain isolated from dog feces was characterized in this study. METHODS AND RESULTS: A multiplex PCR assay was used to detect the presence of colistin-resistant mcr genes; it was found that E. coli QDFD216 co-harbored the mcr-1 and mcr-3 genes. Whole-genome sequencing and further bioinformatics analysis revealed that E. coli QDFD216 belonged to serotype O176:H11, fimH1311 type and ST132. The resistance genes bla CTX-M-14, mdfA, dfrA3, acrA, acrB, tolc, and sul3 were present in the chromosome. The mcr-1.1 and mcr-3.7 genes were located in two plasmids of different incompatibility groups. mcr-1.1 was carried by a IncX4-type plasmid within an typical IS26-parA-mcr-1.1-pap2 cassette, while mcr-3.7 was encoded by an IncP1-type plasmid with a genetic structure of TnAs2-mcr-3.7-dgkA-IS26. No additional antibiotic resistance genes were carried by either plasmid. CONCLUSION: This is the first report of an E. coli isolate co-harboring a mcr-1.1-carrying IncX4 plasmid and a mcr-3.7-carrying IncP1 plasmid. The evolution and mechanism of mcr gene co-existence need further study to assess its impact on public health.
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BACKGROUND: Nano-sized extracellular vesicles secreted by cells play key roles in intercellular crosstalk, and appear to be an excellent biocompatible material as therapeutic cargoes in vivo. Previously, we have demonstrated that miR-204-5p is a key tumor suppressor that could inhibit tumor growth, metastasis and chemoresistance. METHODS: A HEK293T cell line stably expressing miR-204-5p (293T-miR-204) was constructed by lentivirus transduction. Fluorescence real-time quantitative PCR (qPCR) was applied to measure the expression of miR-204-5p. CCK-8 and colony formation assays were used to evaluate the in vitro anticancer effects, and the flow cytometry was used to detect apoptosis. The in vivo therapeutic effects of exosomal miR-204-5p were evaluated using a xenograft mouse model. Western blots were used to detect the protein levels of CD63, Flotillin-2, RAB22A and Bcl2. The protein levels of RAB22A and Bcl2 in tumor tissues were measured by immunohistochemistry staining. RESULTS: MiR-204-5p was clearly upregulated in CRC cells after coculturing with 293T-miR-204 cell-derived conditioned medium (CM) or exosomes. CCK-8 and colony formation assays showed that the cell proliferation ability of CRC cells was clearly inhibited by 293T-miR-204 cell-derived CM or exosomes. The inhibitory effects of exosomal miR-204-5p on cell proliferation were further confirmed in other types of cancers. Exosomal miR-204-5p could induce apoptosis and increase the sensitivity of cancer cells to the chemotherapeutic drug-5-fluorourcil. In addition, exosomal miR-204-5p inhibited the tumor growth in mice. Western blot assay and IHC staining showed that the protein levels of miR-204-5p targets were clearly decreased in cancer cells or xenograft tissues treated with exosomal miR-204-5p. CONCLUSIONS: In this study, we confirmed that exosomal miR-204-5p could efficiently inhibit cancer cell proliferation, induce apoptosis and increase chemosensitivity by specifically suppressing the target genes of miR-204-5p in human cancer cells.