Nanosize Non‐Viral Gene Therapy Reverses Senescence Reprograming Driven by PBRM1 Deficiency to Suppress iCCA Progression

衰老 基因 癌症研究 生物 医学 遗传学
作者
Xiwen Wu,Yi Zhang,Yuan Ding,Jiali Yang,Zimin Song,Shuirong Lin,Ruhe Zhang,Jun Wu,Shunli Shen
出处
期刊:Advanced Science [Wiley]
被引量:1
标识
DOI:10.1002/advs.202414525
摘要

Abstract Polybromo‐1 (PBRM1) serves as a crucial regulator of gene transcription in various tumors, including intrahepatic cholangiocarcinoma (iCCA). However, the exact role of PBRM1 in iCCA and the mechanism by which it regulates downstream target genes remain unclear. This research has revealed that PBRM1 is significantly downregulated in iCCA tissues, and this reduced expression is linked to aggressive clinicopathological features and a poor prognosis. Furthermore, it is demonstrated that PBRM1 can impede iCCA progression, and a gene therapy nanomedicine is developed to treat iCCA in vivo by modulating PBRM1 expression. The heightened expression of PBRM1 induces by the nanomedicine substantially inhibited tumor growth in iCCA. Conversely, the decrease in PBRM1 results in the abnormal activation of the ERK1/2 signaling pathway, a reduction in p16, p53/p21, and cellular senescence, thereby promoting iCCA advancement. Treatment with U0126, an ERK1/2 inhibitor, effectively halted iCCA progression by regulating the PBRM1‐ERK1/2‐cellular senescence pathway. These findings underscore the significant role of PBRM1 in controlling iCCA progression and predicting prognosis. Targeting the PBRM1‐ERK1/2‐cellular senescence pathway with U0126 shows promise for clinical applications in treating iCCA.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
烟花应助蓝色采纳,获得10
1秒前
mawenxing完成签到,获得积分10
1秒前
小王贼棒发布了新的文献求助10
1秒前
飞快的不尤完成签到,获得积分10
1秒前
寒冷无色完成签到,获得积分10
1秒前
2秒前
研友_Raven发布了新的文献求助10
3秒前
3秒前
想要有直升机完成签到,获得积分20
4秒前
zzz完成签到,获得积分10
4秒前
4秒前
Abner完成签到,获得积分10
5秒前
6秒前
6秒前
xinyu应助xiaoYang采纳,获得10
6秒前
6秒前
SUV发布了新的文献求助10
7秒前
7秒前
8秒前
领导范儿应助raibow9814采纳,获得10
9秒前
9秒前
打卡下班应助郎谋采纳,获得10
10秒前
康康完成签到,获得积分20
10秒前
Lucas应助科研通管家采纳,获得10
10秒前
NexusExplorer应助科研通管家采纳,获得10
10秒前
Jasper应助科研通管家采纳,获得10
10秒前
刻苦小蜜蜂应助科研通管家采纳,获得100
10秒前
小蘑菇应助科研通管家采纳,获得10
10秒前
丘比特应助科研通管家采纳,获得10
10秒前
11秒前
FashionBoy应助科研通管家采纳,获得10
11秒前
小蘑菇应助科研通管家采纳,获得10
11秒前
科研通AI5应助科研通管家采纳,获得30
11秒前
11秒前
11秒前
Joshua应助科研通管家采纳,获得10
11秒前
11秒前
星辰大海应助科研通管家采纳,获得10
11秒前
11秒前
11秒前
高分求助中
(禁止应助)【重要!!请各位详细阅读】【科研通的精品贴汇总】 10000
Semantics for Latin: An Introduction 1099
Robot-supported joining of reinforcement textiles with one-sided sewing heads 780
水稻光合CO2浓缩机制的创建及其作用研究 500
Logical form: From GB to Minimalism 500
2025-2030年中国消毒剂行业市场分析及发展前景预测报告 500
镇江南郊八公洞林区鸟类生态位研究 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4165333
求助须知:如何正确求助?哪些是违规求助? 3700835
关于积分的说明 11684501
捐赠科研通 3389754
什么是DOI,文献DOI怎么找? 1859032
邀请新用户注册赠送积分活动 919459
科研通“疑难数据库(出版商)”最低求助积分说明 832090