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增强鼻咽癌细胞放射敏感性的 //信号转导子和转录激活子 1/叉头框 O-1 轴。

Enhances Nasopharyngeal Carcinoma Cell Radiosensitivity the //Signal Transducer and Activator of Transcription-1/Forkhead Box O-1 Axis.

机构信息

Department of Pediatric Otolaryngology, The First People's Hospital of Chenzhou, Hunan Province 423000, China.

Department of Pediatric Gastroenterology, The First People's Hospital of Chenzhou, Hunan Province 423000, China.

出版信息

Dis Markers. 2022 Aug 26;2022:5699275. doi: 10.1155/2022/5699275. eCollection 2022.

Abstract

Nasopharyngeal carcinoma (NPC) is a common malignancy of the nasopharynx, and radioresistant represents the main obstacle in NPC treatment. Malignant transformation of normal cells is driven by genetic and epigenetic changes, which are primarily manifested as changes in miRNA levels and DNA methylation status. microRNA (miR)-613 plays an inhibitory role in several types of cancer. Herein, the current study sought to explore the roles of in NPC cell radiosensitivity. expression patterns in NPC tissues were detected, and its correlation with clinical indexes was analyzed. NP-69 and C666-1 cell lines were selected for cellular experimentation. Radioresistant cell line C666-1R was obtained by fractionated radiation. Cell viability, survival fraction, and apoptosis were detected by CCK-8, colony formation assay, and flow cytometry. The binding relation between and was verified by dual-luciferase and RIP assays. was lowly expressed in NPC tissues and cells, with lower expression levels in C666-1R than C666-1, and further correlated with lymph node metastasis, tumor size, and tumor metastasis. overexpression reduced C666-1R cell viability and survival fraction and increased apoptosis, while C666-1 cells with silencing presented the opposite trends. targeted . and overexpression led to enhanced C666-1R cell viability and survival fraction and decreased apoptosis. reduced methylation and elevated protein level by inhibiting . enhanced NPC radiosensitivity by inhibiting the //STAT1/FOXO1 pathway. Collectively, inhibited , reduced methylation, and increased protein level, thus inhibiting the STAT1/FOXO1 pathway and enhancing the radiosensitivity of NPC cells.

摘要

鼻咽癌(NPC)是一种常见的鼻咽恶性肿瘤,放射抵抗是 NPC 治疗的主要障碍。正常细胞的恶性转化受遗传和表观遗传变化的驱动,主要表现为 miRNA 水平和 DNA 甲基化状态的变化。miR-613 在几种类型的癌症中发挥抑制作用。在此,本研究旨在探讨 miR-613 在 NPC 细胞放射敏感性中的作用。检测 NPC 组织中 miR-613 的表达模式,并分析其与临床指标的相关性。选择 NP-69 和 C666-1 细胞系进行细胞实验。通过分次照射获得耐辐射细胞系 C666-1R。通过 CCK-8、集落形成实验和流式细胞术检测细胞活力、存活分数和细胞凋亡。通过双荧光素酶和 RIP 测定验证 miR-613 和 的结合关系。miR-613 在 NPC 组织和细胞中低表达,C666-1R 中的表达水平低于 C666-1,且与淋巴结转移、肿瘤大小和肿瘤转移进一步相关。过表达 miR-613 降低 C666-1R 细胞活力和存活分数并增加细胞凋亡,而沉默 miR-613 的 C666-1 细胞则呈现相反的趋势。 靶向 。miR-613 过表达导致 C666-1R 细胞活力和存活分数增加,凋亡减少。 通过抑制 降低 甲基化并上调 蛋白水平。 通过抑制 //STAT1/FOXO1 通路增强 NPC 放射敏感性。综上所述,miR-613 通过抑制 降低 甲基化并上调 蛋白水平,从而抑制 STAT1/FOXO1 通路,增强 NPC 细胞的放射敏感性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9459/9439912/17c5aa8870e7/DM2022-5699275.001.jpg

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