{"title":"使用cy5.5标记的反义寡核苷酸对肺癌和表皮癌细胞中MALAT1表达的荧光成像","authors":"Zhenfeng Liu, Chengjun Yao, Haopeng Ni, Guolin Wang, Mengjie Dong","doi":"10.1186/s40644-025-00903-y","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The long noncoding RNA Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) has been extensively studied as an oncogenic factor. Antisense oligonucleotides (ASOs) labeled with the Cyanine5.5 (Cy5.5) dye enable effective in vivo imaging using near-infrared fluorescence.</p><p><strong>Methods: </strong>Pan-cancer research on MALAT1 expression levels was conducted through The Cancer Genome Atlas (TCGA) database analysis. The selectivity and specificity of MALAT1-ASO were validated in lung cancer and epidermal carcinoma cell lines (A549, A431, PC9GR, and PC9) using cellular fluorescence and flow cytometry. Corresponding xenograft models were created for these cell lines, and near-infrared fluorescence imaging assessed tumor imaging effectiveness and the biodistribution of Cy5.5-labeled MALAT1 ASOs.</p><p><strong>Results: </strong>MALAT1 expression levels were found to be upregulated in various tumors and high MALAT1 expression level correlated to poor prognosis in some tumors. The high expression of MALAT1 was confirmed in tumor cell lines. In vitro fluorescent intensity correlated with MALAT1 expression within cells. The fluorescence intensity also exhibited concentration dependence. In vivo experiments revealed a significant contrast between tumor tissues and normal tissues within 24 h. Tumors exhibited varied probe uptake corresponding to their MALAT1 expression levels. Ex vivo experiments shows high probe uptake in kidney, liver and intestine tissues.</p><p><strong>Conclusion: </strong>MALAT1 is highly expressed in various cancer tissues and associated with poor prognosis. In xenograft models of lung cancer and epidermal carcinoma cell lines A549, A431, PC9GR, and PC9, Cy5.5-labeled ASOs exhibit evident binding specificity and discernible imaging effect in both in vitro and in vivo, effectively reflecting MALAT1 expression levels in tumors.</p>","PeriodicalId":9548,"journal":{"name":"Cancer Imaging","volume":"25 1","pages":"82"},"PeriodicalIF":3.5000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211275/pdf/","citationCount":"0","resultStr":"{\"title\":\"Fluorescence imaging of MALAT1 expression using a Cy5.5-labeled antisense oligonucleotide in lung cancer and epidermal carcinoma cells.\",\"authors\":\"Zhenfeng Liu, Chengjun Yao, Haopeng Ni, Guolin Wang, Mengjie Dong\",\"doi\":\"10.1186/s40644-025-00903-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The long noncoding RNA Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) has been extensively studied as an oncogenic factor. Antisense oligonucleotides (ASOs) labeled with the Cyanine5.5 (Cy5.5) dye enable effective in vivo imaging using near-infrared fluorescence.</p><p><strong>Methods: </strong>Pan-cancer research on MALAT1 expression levels was conducted through The Cancer Genome Atlas (TCGA) database analysis. The selectivity and specificity of MALAT1-ASO were validated in lung cancer and epidermal carcinoma cell lines (A549, A431, PC9GR, and PC9) using cellular fluorescence and flow cytometry. Corresponding xenograft models were created for these cell lines, and near-infrared fluorescence imaging assessed tumor imaging effectiveness and the biodistribution of Cy5.5-labeled MALAT1 ASOs.</p><p><strong>Results: </strong>MALAT1 expression levels were found to be upregulated in various tumors and high MALAT1 expression level correlated to poor prognosis in some tumors. The high expression of MALAT1 was confirmed in tumor cell lines. In vitro fluorescent intensity correlated with MALAT1 expression within cells. The fluorescence intensity also exhibited concentration dependence. In vivo experiments revealed a significant contrast between tumor tissues and normal tissues within 24 h. Tumors exhibited varied probe uptake corresponding to their MALAT1 expression levels. Ex vivo experiments shows high probe uptake in kidney, liver and intestine tissues.</p><p><strong>Conclusion: </strong>MALAT1 is highly expressed in various cancer tissues and associated with poor prognosis. 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引用次数: 0
摘要
背景:长链非编码RNA转移相关肺腺癌转录本1 (MALAT1)作为一种致癌因子已被广泛研究。用Cyanine5.5 (Cy5.5)染料标记的反义寡核苷酸(ASOs)可以使用近红外荧光进行有效的体内成像。方法:通过The Cancer Genome Atlas (TCGA)数据库分析,对MALAT1在泛癌中的表达水平进行研究。利用细胞荧光和流式细胞术验证了MALAT1-ASO在肺癌和表皮癌细胞系(A549、A431、PC9GR和PC9)中的选择性和特异性。对这些细胞系建立相应的异种移植模型,近红外荧光成像评估肿瘤成像效果和cy5.5标记的MALAT1 ASOs的生物分布。结果:MALAT1在多种肿瘤中表达上调,部分肿瘤中MALAT1高表达与预后不良相关。MALAT1的高表达在肿瘤细胞系中得到证实。体外荧光强度与细胞内MALAT1表达相关。荧光强度也表现出浓度依赖性。体内实验显示肿瘤组织与正常组织在24小时内存在显著差异。肿瘤表现出不同的探针摄取,对应于其MALAT1表达水平。离体实验显示探针在肾、肝和肠组织中有较高的吸收。结论:MALAT1在多种肿瘤组织中高表达,与不良预后相关。在肺癌和表皮癌细胞系A549、A431、PC9GR和PC9的异种移植模型中,cy5.5标记的ASOs在体外和体内均表现出明显的结合特异性和明显的成像效果,有效反映了肿瘤中MALAT1的表达水平。
Fluorescence imaging of MALAT1 expression using a Cy5.5-labeled antisense oligonucleotide in lung cancer and epidermal carcinoma cells.
Background: The long noncoding RNA Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) has been extensively studied as an oncogenic factor. Antisense oligonucleotides (ASOs) labeled with the Cyanine5.5 (Cy5.5) dye enable effective in vivo imaging using near-infrared fluorescence.
Methods: Pan-cancer research on MALAT1 expression levels was conducted through The Cancer Genome Atlas (TCGA) database analysis. The selectivity and specificity of MALAT1-ASO were validated in lung cancer and epidermal carcinoma cell lines (A549, A431, PC9GR, and PC9) using cellular fluorescence and flow cytometry. Corresponding xenograft models were created for these cell lines, and near-infrared fluorescence imaging assessed tumor imaging effectiveness and the biodistribution of Cy5.5-labeled MALAT1 ASOs.
Results: MALAT1 expression levels were found to be upregulated in various tumors and high MALAT1 expression level correlated to poor prognosis in some tumors. The high expression of MALAT1 was confirmed in tumor cell lines. In vitro fluorescent intensity correlated with MALAT1 expression within cells. The fluorescence intensity also exhibited concentration dependence. In vivo experiments revealed a significant contrast between tumor tissues and normal tissues within 24 h. Tumors exhibited varied probe uptake corresponding to their MALAT1 expression levels. Ex vivo experiments shows high probe uptake in kidney, liver and intestine tissues.
Conclusion: MALAT1 is highly expressed in various cancer tissues and associated with poor prognosis. In xenograft models of lung cancer and epidermal carcinoma cell lines A549, A431, PC9GR, and PC9, Cy5.5-labeled ASOs exhibit evident binding specificity and discernible imaging effect in both in vitro and in vivo, effectively reflecting MALAT1 expression levels in tumors.
Cancer ImagingONCOLOGY-RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
CiteScore
7.00
自引率
0.00%
发文量
66
审稿时长
>12 weeks
期刊介绍:
Cancer Imaging is an open access, peer-reviewed journal publishing original articles, reviews and editorials written by expert international radiologists working in oncology.
The journal encompasses CT, MR, PET, ultrasound, radionuclide and multimodal imaging in all kinds of malignant tumours, plus new developments, techniques and innovations. Topics of interest include:
Breast Imaging
Chest
Complications of treatment
Ear, Nose & Throat
Gastrointestinal
Hepatobiliary & Pancreatic
Imaging biomarkers
Interventional
Lymphoma
Measurement of tumour response
Molecular functional imaging
Musculoskeletal
Neuro oncology
Nuclear Medicine
Paediatric.