Super-enhancer-associated circPVT1 promotes malignancy of hepatocellular carcinoma via YBX1-mediated RRM2 activation

被引:0
|
作者
Chen, Yunhao [1 ,2 ,3 ,4 ]
Du, Chengli [1 ]
Tang, Jie [1 ]
Zhao, Yanchun [5 ]
Xie, Haiyang [2 ,3 ,4 ,6 ]
Zheng, Shusen [2 ,3 ,4 ,6 ]
Tu, Zhengliang [1 ]
机构
[1] Zhejiang Univ, Affiliated Hosp 1, Sch Med, Dept Thorac Surg, Hangzhou 310000, Peoples R China
[2] NHC Key Lab Combined Multiorgan Transplantat, Key Lab Organ Transplantat, Hangzhou, Zhejiang, Peoples R China
[3] Chinese Acad Med Sci 2019RU019, Res Unit Collaborat Diag & Treatment Hepatobiliary, Key Lab Diag & Treatment Organ Transplantat, Hangzhou, Peoples R China
[4] Natl Clin Res Ctr Infect Dis, State Key Lab Diag & Treatment Infect Dis, Hangzhou, Peoples R China
[5] Zhejiang Univ, Affiliated Hosp 1, Dept Hematol, Sch Med, Hangzhou 310000, Peoples R China
[6] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Div Hepatobiliary & Pancreat Surg,Dept Surg, Hangzhou 310000, Peoples R China
基金
中国国家自然科学基金; 中国博士后科学基金;
关键词
Hepatocellular carcinoma (HCC); Circular RNAs (circRNAs); Super-enhancers (SEs); circPVT1; RRM2; CELL IDENTITY; CANCER; ROLES; YB-1;
D O I
10.1016/j.canlet.2024.217395
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Circular RNAs (circRNAs), the essential members of epigenetic reprogramming, are emerging as an appealing layer in hepatocellular carcinoma (HCC). Super-enhancers (SEs) are large clusters of transcriptional enhancers with the tremendous gene activation potential and are extensively investigated in cancer research. The present study explores and uncovers an SE-related circRNA circPVT1, identifying its biological functions and downstream mechanisms in HCC. CircPVT1 is upregulated in HCC, serving as an independent prognostic factor for patients with HCC. Enrichment of H3K27ac and H3K4me1 modifications has been confirmed at the genomic loci of circPVT1's host gene, and the expression of circPVT1 is triggered by SEs. Functionally, circPVT1 enhances cell propagation and mobility capabilities in vitro, and facilitates tumour growth and metastasis in vivo. Mechanistically, circPVT1 recruits YBX1 into the cell nucleus, promoting the transcription of RRM2. Dysregulation of the circPVT1-RRM2 axis advances HCC malignancy, while inhibition of RRM2 or SE alleviates the effects of circPVT1 overexpression. In conclusion, our work demonstrates that circPVT1 is driven by super-enhancers. CircPVT1 promotes HCC progression via YBX1-mediated transcriptional activation of RRM2. These findings provide constructive insights into exploring the pathogenesis of HCC.
引用
收藏
页数:13
相关论文
共 50 条
  • [1] Super-Enhancer-Associated Long Noncoding RNA HCCL5 Is Activated by ZEB1 and Promotes the Malignancy of Hepatocellular Carcinoma
    Peng, Li
    Jiang, Binyuan
    Yuan, Xiaoqing
    Qiu, Yuntan
    Peng, Jiangyun
    Huang, Yongsheng
    Zhang, Chaoyang
    Zhang, Yin
    Lin, Zhaoyu
    Li, Jinsong
    Yao, Weicheng
    Deng, Weixi
    Zhang, Yaqin
    Meng, Meng
    Pan, Xi
    Li, Chunquan
    Yin, Dong
    Bi, Xinyu
    Li, Guancheng
    Lin, De-Chen
    CANCER RESEARCH, 2019, 79 (03) : 572 - 584
  • [2] LncRNA USP2-AS1 Promotes Hepatocellular Carcinoma Growth by Enhancing YBX1-Mediated HIF1α Protein Translation Under Hypoxia
    Chen, Shi-Ping
    Zhu, Gui-Qi
    Xing, Xiao-Xia
    Wan, Jing-Lei
    Cai, Jia-Liang
    Du, Jun-Xian
    Song, Li-Na
    Dai, Zhi
    Zhou, Jian
    FRONTIERS IN ONCOLOGY, 2022, 12
  • [3] LncOCMRL1 promotes oral squamous cell carcinoma growth and metastasis via the RRM2/EMT pathway
    Lu, Nan
    Jiang, Qiming
    Xu, Tianshu
    Gao, Qiyuan
    Wang, Yuepeng
    Huang, Zixian
    Huang, Zhiquan
    Xu, Xiaoding
    JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2024, 43 (01)
  • [4] Resveratrol promotes mitophagy via the MALAT1/miR-143-3p/RRM2 axis and suppresses cancer progression in hepatocellular carcinoma
    Feng, Chun-yan
    Cai, Cheng-song
    Shi, Xiao-qian
    Zhang, Zhi-juan
    Su, Dan
    Qiu, Yun-qing
    JOURNAL OF INTEGRATIVE MEDICINE-JIM, 2025, 23 (01): : 79 - 92
  • [5] Resveratrol promotes mitophagy via the MALAT1/miR-143-3p/RRM2 axis and suppresses cancer progression in hepatocellular carcinoma
    Chunyan Feng
    Chengsong Cai
    Xiaoqian Shi
    Zhijuan Zhang
    Dan Su
    Yunqing Qiu
    Journal of Integrative Medicine, 2025, 23 (01) : 79 - 92
  • [6] SCYL1-BP1 Affects Cell Cycle Arrest in Human Hepatocellular Carcinoma Cells via Cyclin F and RRM2
    Wang, Yang
    Zhi, Qiaoming
    Ye, Qin
    Zhou, Chengyuan
    Zhang, Lei
    Yan, Wei
    Wu, Qun
    Zhang, Di
    Li, Pu
    Huo, Keke
    ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, 2016, 16 (04) : 440 - 446
  • [7] UHRF2 promotes the malignancy of hepatocellular carcinoma by PARP1 mediated autophagy
    Zhang, Yiqi
    Wu, Kejia
    Liu, Yuxin
    Sun, Shuangling
    Shao, Yue
    Li, Qingxiu
    Sui, Xinying
    Duan, Changzhu
    CELLULAR SIGNALLING, 2023, 109
  • [8] YY1 Complex Promotes Quaking Expression via Super-Enhancer Binding during EMT of Hepatocellular Carcinoma
    Han, Jingxia
    Meng, Jing
    Chen, Shuang
    Wang, Xiaorui
    Yin, Shan
    Zhang, Qiang
    Liu, Huijuan
    Qin, Rong
    Li, Zhongwei
    Zhong, Weilong
    Zhang, Chao
    Zhang, Heng
    Tang, Yuanhao
    Lin, Tingting
    Gao, Wanfeng
    Zhang, Xiaoyun
    Yang, Lan
    Liu, Yanrong
    Zhou, Hong-Gang
    Sun, Tao
    Yang, Cheng
    CANCER RESEARCH, 2019, 79 (07) : 1451 - 1464
  • [9] BAIAP2L2 promotes the malignancy of hepatocellular carcinoma via GABPB1-mediated reactive oxygen species imbalance
    Jia, Wenbo
    Xu, Bin
    Yu, Liang
    Feng, Yanzhi
    Wang, Jinyi
    Xu, Chao
    Liang, Litao
    Zhou, Yongping
    Ding, Wenzhou
    Kong, Lianbao
    CANCER GENE THERAPY, 2024, 31 (12) : 1868 - 1883
  • [10] The long non-coding RNA PIK3CD-AS2 promotes lung adenocarcinoma progression via YBX1-mediated suppression of p53 pathway
    Zheng, Xiufen
    Zhang, Junying
    Fang, Tian
    Wang, Xiaoxiao
    Wang, Siwei
    Ma, Zhifei
    Xu, Youtao
    Han, Chencheng
    Sun, Mengting
    Xu, Lin
    Wang, Jie
    Yin, Rong
    ONCOGENESIS, 2020, 9 (03)