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在HeLa细胞中敲低Hsa_circ_0009910可增加miR-198表达水平,并降低c-Met表达水平和细胞活力。

Hsa_circ_0009910 knockdown in HeLa cells increases miR‑198 expression levels and decreases c‑Met expression levels and cell viability.

作者信息

Tolentino-Molina Bernardo Xavier, Loaeza-Loaeza Jaqueline, Ortega-Soto Arturo, Castro-Coronel Yaneth, Fernández-Tilapa Gloria, Hernández-Sotelo Daniel

机构信息

Laboratory of Cancer Epigenetics, School of Chemical and Biological Sciences, Autonomous University of Guerrero, Chilpancingo, Guerrero 39070, Mexico.

Laboratory of Neurotoxicology, Department of Toxicology, Center for Research and Advanced Studies of the National Polytechnic Institute, Mexico City 07300, Mexico.

出版信息

Oncol Lett. 2024 Nov 26;29(2):74. doi: 10.3892/ol.2024.14820. eCollection 2025 Feb.

Abstract

Cervical cancer (CC) is considered a public health problem. Circular RNAs (circRNAs) serve important roles in different types of cancer, including CC. However, the mechanisms used by circRNAs to facilitate CC progression are currently unclear. The present study analyzed the effects of hsa_circ_0009910 knockdown on microRNA (miRNA/miR)-198 and mesenchymal-epithelial transition factor (c-Met) expression levels and its impact on apoptosis and the viability of HeLa cells. Differentially expressed circRNAs in CC were identified using analysis of circRNA microarray data. Bioinformatics analysis was performed to predict circRNA-microRNA (miRNA) and miRNA-mRNA interactions. The knockdown of hsa_circ_0009910 in HeLa cells was performed using small interfering RNA and the expression levels of hsa_circ_0009910, miR-198 and c-Met were assessed using reverse transcription-quantitative PCR. The viability and apoptosis of HeLa cells were evaluated using MTT, neutral red uptake and ApoLive-Glo™ multiplex assays. Hsa_circ_0009910 was significantly upregulated in HeLa cells and the knockdown of hsa_circ_0009910 increased miRNA-198 expression levels, reduced c-Met expression levels and decreased cellular viability, but not apoptosis, in HeLa cells. Overall, these results indicated that hsa_circ_0009910 could act as a molecular sponge of miRNA-198 and contribute to the upregulation of c-Met expression levels. The hsa_circ_0009910/miRNA-198/c-Met interaction network affects the viability, but not apoptosis, of HeLa cells. Based on this mechanism, the present study suggests that hsa_circ_0009910 may be a promising biomarker for CC.

摘要

宫颈癌(CC)被视为一个公共卫生问题。环状RNA(circRNAs)在包括CC在内的不同类型癌症中发挥重要作用。然而,目前尚不清楚circRNAs促进CC进展的机制。本研究分析了hsa_circ_0009910敲低对微小RNA(miRNA/miR)-198和间充质-上皮转化因子(c-Met)表达水平的影响及其对HeLa细胞凋亡和活力的影响。通过分析circRNA微阵列数据鉴定CC中差异表达的circRNAs。进行生物信息学分析以预测circRNA-微小RNA(miRNA)和miRNA-信使核糖核酸(mRNA)的相互作用。使用小干扰RNA对HeLa细胞中的hsa_circ_0009910进行敲低,并使用逆转录定量聚合酶链反应评估hsa_circ_0009910、miR-198和c-Met的表达水平。使用MTT、中性红摄取和ApoLive-Glo™多重检测评估HeLa细胞的活力和凋亡。hsa_circ_0009910在HeLa细胞中显著上调,hsa_circ_0009910的敲低增加了miRNA-198的表达水平,降低了c-Met的表达水平,并降低了HeLa细胞的细胞活力,但未影响细胞凋亡。总体而言,这些结果表明hsa_circ_0009910可能作为miRNA-198的分子海绵,并有助于上调c-Met的表达水平。hsa_circ_0009910/miRNA-198/c-Met相互作用网络影响HeLa细胞的活力,但不影响其凋亡。基于这一机制,本研究表明hsa_circ_0009910可能是CC的一个有前景的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a59a/11622005/ec07ab725b1e/ol-29-02-14820-g00.jpg

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