在宫癌发生过程中,HPV16集成通过c-Myc/miR-142-5p/HOXA5/SLC7A11轴调节铁灭菌耐药性
Xiao-Jing Chen1,2, Chu-Hong Guo1, Yang Yang1,3
1Department of Obstetrics and Gynecology, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Road, Yuexiu District, Guangzhou, 510120, People's Republic of China.
高风险的HPV16集成通过激活c-Myc/miR-142-5p/HOXA5/SLC7A11通路,促进子宫癌中的铁灭抵抗. 这一发现为HPV16相关的宫平细胞癌提供了潜在的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞死亡研究 细胞死亡研究
背景情况:
- 铁亡是一种受调节的细胞死亡形式,与病毒相关的癌症有关.
- 在高风险的人类乳头瘤病毒 (HPV) 集成的瘤中铁灭的作用尚不清楚.
研究的目的:
- 调查高风险HPV16整合与宫状状细胞癌 (CSCC) 的铁化之间的关联.
- 阐明HPV16集成的CSCC中铁亡调节的基础分子机制.
主要方法:
- 使用高通量病毒整合检测 (HIVID) 分析了HPV16的整合.
- 用埃拉斯诱导铁亡,并通过脂质反应性氧物种 (ROS),甲酸 (MDA),细胞内Fe2+水平和传输电子显微镜 (TEM) 评估其水平.
- 使用临床宫样本和体内异种移植模型.
主要成果:
- 在CSCC进展中,HPV16整合热点c-Myc表达与ferroptosis负相关.
- 上调的miR-142-5p,c-Myc的下游,抑制了铁灭.
- HOXA5,是miR-142-5p的标,降低了SLC7A11的调节,减少了细胞内Fe2+和脂质过氧化物.
- 通过促进ferroptosis in vitro和 in vivo,c-Myc knockdown增强了埃拉斯的抗瘤活性.
结论:
- 通过miR-142-5p/HOXA5/SLC7A11轴,HPV16集成热点c-Myc通过miR-142-5p/HOXA5/SLC7A11轴驱动铁灭菌抵抗.
- 这一途径代表了HPV16整合相关的CSCC的新型治疗标.
更多相关视频
07:43Four-color Fluorescence Immunohistochemistry of T-cell Subpopulations in Archival Formalin-fixed, Paraffin-embedded Human Oropharyngeal Squamous Cell Carcinoma Samples
Published on: July 29, 2017
10:26RNAscope for In situ Detection of Transcriptionally Active Human Papillomavirus in Head and Neck Squamous Cell Carcinoma
Published on: March 11, 2014
相关概念视频
Induced Pluripotent Stem Cells
Somatic...
Abnormal Proliferation
Rous Sarcoma Virus (RSV) and Cancer
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
Mechanisms of Retrovirus-induced Cancers
