首页|Exosome-Transmitted miR-224-5p Promotes Colorectal Cancer Cell Proliferation via Targeting ULK2 in p53-Dependent Manner

Exosome-Transmitted miR-224-5p Promotes Colorectal Cancer Cell Proliferation via Targeting ULK2 in p53-Dependent Manner

扫码查看
Objective To investigate the role and molecular mechanism of exosomal miR-224-5p in colorectal cancer (CRC).Methods The miR-224-5p expression in CRC patient tissues and cell-derived exosomes was measured by laser capture microdissection and qRT-PCR, respectively. Dual-luciferase reporter gene assay was used to determine the target gene of miR-224-5p. The protein expressions of p53 and unc-51 like kinase 2 (ULK2) in CRC cells were detected by western blot. Flow cytometry was used to detect cell cycle and apoptosis. Cell proliferation was measured by CCK8 and EdU assay.Results The miR-224-5p expression was upregulated in CRC tissues and increased progressively with the rise of CRC stage. CRC cells secreted extracellular miR-224-5p mainly in an exosome-dependent manner, and then miR-224-5p could be transferred to surrounding tumor cells to regulate cell proliferation in the form of autocrine or paracrine. Moreover, ULK2 was characterized as a direct target of miR-224-5p and was downregulated in CRC tissues. Interestingly, ULK2 inhibited CRC cell proliferation in a p53-dependent manner. Furthermore, exosome-derived miR-224-5p partially reversed the proliferation regulation of ULK2 on CRC cells.Conclusion Our findings demonstrate that exosome-transmitted miR-224-5p promotes p53-dependent cell proliferation by targeting ULK2 in CRC, which may offer promising targets for CRC prevention and therapy.

miR-224-5pExosomeULK2p53Cell proliferationColorectal cancer

YANG Le Mei、ZHENG Qi、LIU Xiao Jia、LI Xian Xian、Veronica Lim、CHEN Qi、ZHAO Zhong Hua、WANG Shu Yang

展开 >

Department of Pathology, School of Basic Medicine, Fudan University, Shanghai 200032, China

Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9054, New Zealand

Department of Pathology, Huashan Hospital, Fudan University, Shanghai 200040, China

Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China

Teladoc Health Inc, Shanghai 200335, China

Shanghai Medical College, Fudan University, Shanghai 200032, China

Shanghai Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention, Shanghai 200032, China

展开 >

National Natural Science Foundation of China

81972803

2024

生物医学与环境科学(英文版)
中国疾病预防控制中心

生物医学与环境科学(英文版)

CSTPCD
影响因子:0.76
ISSN:0895-3988
年,卷(期):2024.37(1)
  • 35