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Particuology 2024年第1期84卷 53-59页

作者： Huatai Zhu Limei Zhang Fujia Kou Jingyang Zhao Jiandu Lei Jing He Beijing Key Laboratory of Lignocellulosic Chemistry Beijing Forestry UniversityBeijing100083China Institute of Biopharmaceutical and Health Engineering Tsinghua Shenzhen International Graduate SchoolTsinghua UniversityShenzhen518055China

Oral colonic nano-drug delivery system has attracted growing attention in treating colon cancer for their excellent ***,the unique and complex structure of the gastrointestinal tract is still an obstacle to the safe delivery of drugs targeting sites in colon ***,we designed magnetically driven dual-targeted oral colonic nanoparticles loaded with chlorogenic acid using pectin and oleic acid-modified iron oxide(Fe3O4@OA).Specific degradation of pectin by pectinase produced by colonic flora and magnetic fields applied to the colon confers specific targeting of nanoparticles to the *** order to overcome the challenge of preparing magnetically driven nanoparticles with small and homogeneous particle sizes by a single conventional method,we developed the combined ultrasound-emulsification *** average particle size of the prepared nanoparticles was 81.04±1.02 nm,which showed good drug release in the simulated colonic *** vitro anticancer studies,the drug-loaded nanoparticles possess an obvious toxicity and apoptosis-inducing ability against cancer ***,the hemolysis results demonstrated the safety of the nanoplatform(PET/CGA/Fe_(3)O_(4)@OA).This work holds broad prospects as a new treatment modality for colon cancer.

关键词： Pectin Chlorogenic acid Ultrasound-emulsion Magnetically driven colon cancer colon targeted

colon cancer screening:What to choose?

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World Journal of Gastrointestinal Oncology 2024年第8期16卷 3393-3396页

作者： Martin Alonso Gomez Zuleta Department of Internal Medicine Head of Gastroenterology UnitUniversidad Nacional de ColombiaHospital Universitario Nacional de ColombiBogota 571Colombia

Colorectal cancer is one of the predominant tumors in the world,primarily generated by a progression from polyp to cancer which can last several years,giving a great opportunity to the scientific community for its prevention by screening programs that can be done with invasive and non-invasive *** this issue,Lopes et al show us an excellent review of screening,its options,its advantages and disadvantages.

关键词： colon cancer Adenoma Screening Fecal immunochemical test colonoscopy

RBM25 depletion suppresses the growth of colon cancer cells through regulating alternative splicing of MNK2

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Science China Life Sciences 2024年第10期67卷 2186-2197页

作者： Lili Zhi Chaoqun Chen Ge Zhang Tian Huang Wenxia He Jinrui Zhang Dan Chen Jiayi Liu Jinyao Zhao Yangfan Qi Guiying Wang Wenjing Zhang Yang Wang Sino-US Research Center for cancer Translational Medicine of the Second Affiliated Hospital of Dalian Medical University & Institute of cancer Stem Cell Dalian Medical University Department of Immunology College of Basic Medical SciencesDalian Medical University Institute of cancer Stem Cell Dalian Medical University Department of Pathology the First Affiliated Hospital of Dalian Medical UniversityDalian Medical University Department of General Surgery the Second Hospital of Hebei Medical University The Second Department of General Surgery the Fourth Hospital of Hebei Medical University Hebei Key Laboratory of Etiology Tracing and Individualized Diagnosis and Treatment for Digestive System Carcinoma

Increasing evidence suggests that deregulated RNA splicing factors play critical roles in tumorigenesis; however, their specific involvement in colon cancer remains largely unknown. Here we report that the splicing factor RBM25 is overexpressed in colon cancer, and this increased expression correlates with a poor prognosis of patients with colon cancer. Functionally, RBM25 ablation suppresses the growth of colon cancer cells both in vitro and in vivo. Mechanistically, our transcriptome-wide analysis of splicing events revealed that RBM25 regulates a large number of cancer-related alternative splicing events across the human genome in colon cancer. Particularly, RBM25 regulates the splicing of MNK2 by interacting with the poly G rich region in exon 14a, thereby inhibiting the selection of the proximal 3'splice site(ss), resulting in the production of the oncogenic short isoform, MNK2b. Knockdown of RBM25 leads to an increase in the MNK2a isoform and a decrease in the MNK2b isoform. Importantly, re-expression of MNK2b or blocking the 3′ ss of the alternative exon 14a with ASO partially reverses the RBM25 knockdown mediated tumor suppression. Moreover, MNK2b levels were significantly increased in colon cancer tissues, which is positively correlated with the expression level of RBM25. Collectively, our findings uncover the critical role of RBM25 as a key splicing factor in colon cancer, suggesting its potential as a prognostic marker and therapeutic target.

关键词： RBM25 colon cancer alternative splicing MNK2

TCP-1,a novel peptide to diagnose early colon cancer

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Chinese Chemical Letters 2024年第3期35卷 226-233页

作者： Hang Yu Baoying Wen Min Huang Ru Feng Libin Pan Manyi Xu Hao Lin Lin Cong Sen Zhang Yan Li Chi-Hin Cho Chongjing Zhang Xiaoguang Chen Yan Wang State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia MedicaChinese Academy of Medical SciencesBeijing 100050China School of Biomedical Sciences Faculty of MedicineThe Chinese University of Hong KongHong KongChina

A nine cyclic peptide(TCP-1)showed excellent specificity for colon ***-1 binds with human tumor tissues at early stages and mice tumor with diameters of 1-4 mm,suggesting that TCP-1 may be used for early diagnosis of colon *** mechanism of the targeted binding of TCP-1 to colon cancer was also studied using immunoprecipitation,LC-MS and *** screening and identifying of the possible binding target proteins of TCP-1,keratin,typeⅡcytoskeletal 5 was speculated to be the specific binding target protein of TCP-1 in human tumor *** studies were conducted to investigate the target-mediated drug disposition of the new tumor-specific peptide by LC-MS/*** tissue distribution study showed that TCP-1 was found only in colon tumors(the target site)in tumor mice did not bind to any other *** TCP-1 to tumor markedly increased its removal rate from blood circulation but mildly extended its staying time in *** tumor mice,a lower AUC of TCP-1(reduced by almost 35%)and 2-fold higher clearance were found compared to that of normal *** proposed metabolic pathway of TCP-1 in the kidney was also determined using LC-MS^(n)-*** high specificity and low toxicity of the peptide may be caused by its extremely tight binding to the *** applications for future clinical use,including MRI and PET/CT were also explored,and this research may promote the development of colon cancer diagnostic technology research and provide new ideas and technical routes for tumor diagnostic technology.

关键词： colon cancer TCP-1 Peptide Cytokeratin 5 Pharmacokinetics/pharmacodynamics(PK/PD)

Humanβ-defensin-1 affects the mammalian target of rapamycin pathway and autophagy in colon cancer cells through long noncoding RNA TCONS_00014506

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1465-1478页

作者： Yu-Xin Zhao Yan Cui Xin-Hong Li Wen-Hong Yang Shi-Xiang An Jia-Xian Cui Min-Yu Zhang Jing-Kun Lu Xuan Zhang Xiu-Mei Wang Li-Li Bao Peng-Wei Zhao Department of Anesthesiology Inner Mongolia Chest HospitalThe Fourth HospitalHohhot 010035Inner Mongolia Autonomous RegionChina College of Humanities and Education Inner Mongolia Medical UniversityHohhot 010059Inner Mongolia Autonomous RegionChina Department of Radiotherapy The Affiliated Hospital of Inner Mongolia Medical UniversityHohhot 010059Inner Mongolia Autonomous RegionChina School of Basic Medical Science Inner Mongolia Medical UniversityHohhot 010059Inner Mongolia Autonomous RegionChina Department of Medical Oncology The Affiliated Cancer Hospital of Inner Mongolia Medical UniversityHohhot 010050Inner Mongolia Autonomous RegionChina

BACKGROUND Colorectal cancer has a low 5-year survival rate and high ***β-defensin-1(hBD-1)may play an integral function in the innate immune system,contributing to the recognition and destruction of cancer *** non-coding RNAs(lncRNAs)are involved in the process of cell differentiation and *** To investigate the effect of hBD-1 on the mammalian target of rapamycin(mTOR)pathway and autophagy in human colon cancer SW620 *** CCK8 assay was utilized for the detection of cell proliferation and determination of the optimal drug *** formation assay was employed to assess the effect of hBD-1 on SW620 cell *** was used to screen potentially biologically significant lncRNAs related to the mTOR ***,p-mTOR(Ser2448),Beclin1,and LC3II/I expression levels in SW620 cells were assessed through Western blot *** hBD-1 inhibited the proliferative ability of SW620 cells,as evidenced by the reduction in the colony formation capacity of SW620 cells upon exposure to ***-1 decreased the expression of p-mTOR(Ser2448)protein and increased the expression of Beclin1 and LC3II/I ***,bioinformatics analysis identified seven lncRNAs(2 upregulated and 5 downregulated)related to the mTOR *** lncRNA TCONS_00014506 was ultimately *** the inhibition of the lncRNA TCONS_00014506,exposure to hBD-1 inhibited p-mTOR(Ser2448)and promoted Beclin1 and LC3II/I protein *** hBD-1 inhibits the mTOR pathway and promotes autophagy by upregulating the expression of the lncRNA TCONS_00014506 in SW620 cells.

关键词： colon cancer Humanβ-defensin-1 LncRNA Mammalian target of rapamycin Autophagy

Role of oncogenic long noncoding RNA KCNQ1OT1 in colon cancer

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Oncology Research 2024年第3期32卷 585-596页

作者： GANG LIU LEI SHI BIN WANG ZEHUI WU HAIYUAN ZHAO TIANYU ZHAO LIANGHUI SHI Department of Gastrointestinal Surgery First ffiliated Hospital of Wannan Medical CollegeWuhu241001China Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences Stomatological Hospital of Chongqing Medical UniversityChongqing401147China

The role of lncRNA KCNQ1 opposite strand/antisense transcript 1(KCNQ1OT1)in colon cancer involves various tumorigenic processes and has been studed ***,the mechanism by which it promotes colon cancer remains *** vector pSEB61 was retroftted in established HCT116 siKCN and SW480-siKCN cells to silence KCNQ1 *** proliferation was measured using CCK8 assay,and flow cytometry(FCM)detected cell cydle *** sequencing(RNA Seq)analysis showed differentially expressed genes(DEGs).Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were carried out to analyze enriched functions and signaling ***-qPCR,immunofluorescence,and western blotting were carried out to validate downstream gene *** effects of tumorigenesis were evaluated in BALB/c nude mice by tumor *** data revealed that the silencing of KONQ1OT1 in HCT116 and SW480 cells slowed cell growth and decreased the number of cells in the G2/M ***-Seq analysis showed the data of DEGs enriched in various GO and KEGG pathways such as DNA replication and cell *** qPCR,immunofluorescence,and western blotting confirmed downstream CCNE2 and PCNA gene ***116 siKCN cells signifcantly suppressed tumorigenesis in BALB/c nude *** study suggests that lncRNA KCNQ1OT1 may provide a promising therapeutic strategy for colon cancer.

关键词： lncRNA KCNQ1OT1 colon cancer HCT116 cells Tumorigenesis

Complement factor Ⅰ knockdown inhibits colon cancer development by affecting Wnt/β-catenin/c-Myc signaling pathway and glycolysis

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2646-2662页

作者： Yong-Jun Du Yue Jiang Yan-Mei Hou Yong-Bo Shi Department of Proctology Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072Sichuan ProvinceChina School of Clinical Medicine Chengdu University of Traditional Chinese MedicineChengdu 610075Sichuan ProvinceChina Department of Proctology Zigong Hospital of Traditional Chinese MedicineZigong 643000Sichuan ProvinceChina

BACKGROUND colon cancer(CC)occurrence and progression are considerably influenced by the tumor ***,the exact underlying regulatory mechanisms remain *** To investigate immune infiltration-related differentially expressed genes(DEGs)in CC and specifically explored the role and potential molecular mechanisms of complement factor I(CFI).METHODS Immune infiltration-associated DEGs were screened for CC using *** reverse transcription polymerase chain reaction was used to examine hub DEGs expression in the CC cell *** CFI-knockdown HT29 and HCT116 cell lines were constructed,and the diverse roles of CFI in vitro were assessed using CCK-8,5-ethynyl-2’-deoxyuridine,wound healing,and transwell *** and eosin staining and immunohistochemistry staining were employed to evaluate the influence of CFI on the tumorigenesis of CC xenograft models constructed using BALB/c male nude *** proteins associated with glycolysis and the Wnt pathway were measured using western *** Six key immune infiltration-related DEGs were screened,among which the expression of CFI,complement factor B,lymphoid enhancer binding factor 1,and SRY-related high-mobility-group box 4 was upregulated,whereas that of fatty acid-binding protein 1,and bone morphogenic protein-2 was ***,CFI could be used as a diagnostic biomarker for ***,CFI silencing inhibited CC cell proliferation,migration,invasion,and tumor ***,CFI knockdown downregulated the expression of key glycolysis-related proteins(glucose transporter type 1,hexokinase 2,lactate dehydrogenase A,and pyruvate kinase M2)and the Wnt pathway-related proteins(β-catenin and c-Myc).Further investigation indicated that CFI knockdown inhibited glycolysis in CC by blocking the Wnt/β-catenin/c-Myc *** The findings of the present study demonstrate that CFI plays a crucial role in CC development by influencing g

关键词： colon cancer Immune infiltration Complement factor I Glycolysis Wnt/β-catenin/c-Myc pathway

Transient receptor potential channels as predictive marker and potential indicator of chemoresistance in colon cancer

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Oncology Research 2024年第1期32卷 227-239页

作者： WEI HU THOMAS WARTMANN MARCO STRECKER ARISTOTELIS PERRAKIS ROLAND CRONER ARPAD SZALLASI WENJIE SHI ULF D.KAHLERT The Fourth Clinical Medical College of Yangzhou University Nantong Rich HospitalNantongChina Molecular and Experimental Surgery Clinic for General-Visceral-Vascular and Transplant SurgeryFaculty of Medicine and University Hospital MagdeburgOtto-von-Guericke UniversityMagdeburgGermany Department of Pathology and Experimental cancer Research Semmelweis UniversityBudapestHungary

Transient receptor potential(TRP)channels are strongly associated with colon cancer development and *** study leveraged a multivariate Cox regression model on publicly available datasets to construct a TRP channels-associated gene signature,with further validation of signature in real world samples from our hospital treated patient ***-Meier(K-M)survival analysis and receiver operating characteristic(ROC)curves were employed to evaluate this gene signature’s predictive accuracy and robustness in both training and testing cohorts,***,the study utilized the CIBERSORT algorithm and single-sample gene set enrichment analysis to explore the signature’s immune infiltration landscape and underlying functional *** support vector machine algorithm was applied to evaluate the signature’s potential in predicting chemotherapy *** findings unveiled a novel three TRP channels-related gene signature(MCOLN1,TRPM5,and TRPV4)in colon adenocarcinoma(COAD).The ROC and K-M survival curves in the training dataset(AUC=0.761;p=1.58e-05)and testing dataset(AUC=0.699;p=0.004)showed the signature’s robust predictive capability for the overall survival of COAD *** of the immune infiltration landscape associated with the signature revealed higher immune infiltration,especially an increased presence of M2 macrophages,in high-risk group patients compared to their low-risk ***-risk score patients also exhibited potential responsiveness to immune checkpoint inhibitor therapy,evident through increased CD86 and PD-1 expression ***,the TRPM5 gene within the signature was highly expressed in the chemoresistance group(p=0.00095)and associated with poor prognosis(p=0.036)in COAD patients,highlighting its role as a hub gene of ***,this signature emerged as an independent prognosis factor for COAD patients(p=6.48e-06)and expression of model gene are validated by public data a

关键词： colon cancer Transient receptor potential channels Prognostic signature Chemotherapy efficiency TRPM5

Clinical outcome and prognostic factors of T4N0M0 colon cancer after R0 resection:A retrospective study

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1869-1877页

作者： Bang Liu Zhao-Xiong Zhang Xin-Yang Nie Wei-Lin Sun Yong-Jia Yan Wei-Hua Fu Department of General Surgery Tianjin Medical University General HospitalTianjin Medical UniversityTianjin 300052China

BACKGROUND Paradoxically,patients with T4N0M0(stage II,no lymph node metastasis)colon cancer have a worse prognosis than those with T2N1-2M0(stage III).However,no previous report has addressed this *** To screen prognostic risk factors for T4N0M0 colon cancer and construct a prognostic nomogram model for these *** Two hundred patients with T4N0M0 colon cancer were treated at Tianjin Medical University General Hospital between January 2017 and December 2021,of which 112 patients were assigned to the training cohort,and the remaining 88 patients were assigned to the validation *** between the training and validation groups were *** training cohort was subjected to multi-variate analysis to select prognostic risk factors for T4N0M0 colon cancer,followed by the construction of a nomogram *** The 3-year overall survival(OS)rates were 86.2%and 74.4%for the training and validation cohorts,***(P=0.000),T stage(P=0.001),right hemicolon(P=0.025),irregular review(P=0.040),and carbohydrate antigen 199(CA199)(P=0.011)were independent risk factors of OS in patients with T4N0M0 colon cancer.A nomogram model with good concordance and accuracy was *** Enterostomy,T stage,right hemicolon,irregular review,and CA199 were independent risk factors for OS in patients with T4N0M0 colon *** nomogram model exhibited good agreement and accuracy.

关键词： T4N0M0 colon cancer Prognosis Multivariate analysis Nomogram colon cancer

Novel miR-490-3p/hnRNPA1-b/PKM2 axis mediates the Warburg effect and proliferation of colon cancer cells via the PI3K/AKT pathway

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2038-2059页

作者： Xiang-Hui Wan Guo-Bing Jin Qun Yang Ji-Long Hu Zhi-Liang Liu Jun Rao Can Wen Peng-Ling Li Xi-Mei Yang Bo Huang Xiao-Zhong Wang Jiangxi Medical College Nanchang UniversityNanchang 330029Jiangxi ProvinceChina Department of Clinical Laboratory Jiangxi Cancer HospitalNanchang 330029Jiangxi ProvinceChina Jiangxi Key Laboratory of Translational Research for cancer Jiangxi Cancer HospitalNanchang 330029Jiangxi ProvinceChina Department of Abdominal Surgery Jiangxi Cancer HospitalNanchang 330029Jiangxi ProvinceChina Department of Pathology Jiangxi Cancer HospitalNanchang 330029Jiangxi ProvinceChina Science and Education Section Jiangxi Cancer HospitalNanchang 330029Jiangxi ProvinceChina Department of Clinical Laboratory Jiangxi Children’s HospitalNanchang 330006Jiangxi ProvinceChina Department of Clinical Laboratory The Second Affiliated Hospital of Nanchang UniversityNanchang 330006Jiangxi ProvinceChina Jiangxi Province Key Laboratory of Laboratory Medicine The Second Affiliated Hospital of Nanchang UniversityNanchang 330006Jiangxi ProvinceChina

BACKGROUND Heterogeneous ribonucleoprotein A1(hnRNPA1)has been reported to enhance the Warburg effect and promote colon cancer(CC)cell proliferation,but the role and mechanism of the miR-490-3p/hnRNPA1-b/PKM2 axis in CC have not yet been *** To investigate the role and mechanism of a novel miR-490-3p/hnRNPA1-b/PKM2 axis in enhancing the Warburg effect and promoting CC cell proliferation through the PI3K/AKT *** Paraffin-embedded pathological sections from 220 CC patients were collected and subjected to immunohistochemical analysis to determine the expression of *** relationship between the expression values and the clinicopathological features of the patients was *** in mRNA expression were analyzed using quantitative real-time polymerase chain reaction,while differences in protein expression were analyzed using western *** proliferation was evaluated using the cell counting kit-8 and 5-ethynyl-2’-deoxyuridine assays,and cell cycle and apoptosis were detected using flow cytometric *** targeted binding of miR-490-3p to hnRNPA1-b was validated using a dual luciferase reporter *** Warburg effect was evaluated by glucose uptake and lactic acid production *** The expression of hnRNPA1-b was significantly increased in CC tissues and cells compared to normal controls(P<0.05).Immunohistochemical results demonstrated significant variations in the expression of the hnRNPA1-b antigen in different stages of CC,including stage I,II-III,and ***,the clinicopathologic characterization revealed a significant correlation between hnRNPA1-b expression and clinical stage as well as T ***1-b was found to enhance the Warburg effect through the PI3K/AKT pathway,thereby promoting proliferation of HCT116 and SW620 ***,the proliferation of HCT116 and SW620 cells was inhibited when miR-490-3p targeted and bound to hnRNPA1-b,effectively blocking the Warburg ***

关键词： Heterogeneous ribonucleoprotein A1-b MiR-490-3p colon cancer Alternative splicing Warburg effect