Tumor cell-derived exosomes mediating hsa_circ_0001739/lncRNA AC159540.1 facilitate liver metastasis in colorectal cancer,Cell Biology and Toxicology

当前位置： X-MOL 学术 › Cell Biol. Toxicol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Tumor cell-derived exosomes mediating hsa_circ_0001739/lncRNA AC159540.1 facilitate liver metastasis in colorectal cancer
Cell Biology and Toxicology ( IF 6.1 ) Pub Date : 2023-11-14 , DOI: 10.1007/s10565-023-09837-2
Cai-Feng Yue ₁ , Ju-Gao Chen ₂ , Zi-Yue Li ₃ , Lai-Sheng Li ₄ , Jie-Rong Chen ₅ , Hai-Xia Xie ₁ , Bin Zhang ₆ , Yun-Miao Guo ₇

Affiliation

Department of Laboratory Medicine, Central People's Hospital of Zhanjiang, Guangdong Medical University Zhanjiang Central Hospital, Zhanjiang, 524045, People's Republic of China.
Department of Oncology, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518020, People's Republic of China.
Prenatal Diagnostic Center and Cord Blood Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China.
Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China.
Department of Laboratory Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People's Republic of China.
Department of Cardiovascular Diagnosis, Central People's Hospital of Zhanjiang, Guangdong Medical University Zhanjiang Central Hospital, Zhanjiang, 524045, People's Republic of China.
Zhanjiang Institute of Clinical Medicine, Central People's Hospital of Zhanjiang, Guangdong Medical University Zhanjiang Central Hospital, Zhanjiang, 524045, People's Republic of China.

Background

The current study probed into how tumor cell-derived exosomes (Exos) mediated hsa_circ_0001739/lncRNA AC159540.1 to manipulate microRNA (miR)-218-5p/FTO-N6-methyladenosine (m6A)/MYC signal axis in liver metastasis in colorectal cancer (CRC).

Methods

hsa_circ_0001739 and lncRNA AC159540.1 were identified as the upstream regulator of miR-218-5p using ENCORI and LncBase databases. Expression patterns of miR-218-5p, hsa_circ_0001739, lncRNA AC159540.1, FTO, and MYC were detected, accompanied by loss-and-gain-of function assays to examine their effects on CRC cell biological functions. SW480 cells-derived Exos were purified, followed by in vitro studies to uncover the effect of hsa_circ_0001739/lncRNA AC159540.

Results

miR-218-5p was downregulated while hsa_circ_0001739/lncRNA AC159540.1 was upregulated in CRC tissues and cells. Silencing of hsa_circ_0001739/lncRNA AC159540.1 restrained the malignant phenotypes of CRC cells. Exos-mediated hsa_circ_0001739/lncRNA AC159540.1 competitively inhibited miR-218-5p to elevate FTO and MYC. The inducing role of Exos-mediated hsa_circ_0001739/lncRNA AC159540.1 in CRC was also validated in vivo.

Conclusion

Conclusively, Exos-mediated circ_0001739/lncRNA AC159540.1 regulatory network is critical for CRC, offering a theoretical basis for CRC treatment.

Graphical abstract

中文翻译：

肿瘤细胞来源的外泌体介导 hsa_circ_0001739/lncRNA AC159540.1 促进结直肠癌肝转移

背景

目前的研究探讨了肿瘤细胞源性外泌体（Exos）如何介导hsa_circ_0001739/lncRNA AC159540.1来操纵结直肠癌肝转移中的microRNA（miR）-218-5p/FTO-N6-甲基腺苷（m6A）/MYC信号轴（CRC）。

方法

使用 ENCORI 和 LncBase 数据库将 hsa_circ_0001739 和 lncRNA AC159540.1 确定为 miR-218-5p 的上游调节因子。检测了 miR-218-5p、hsa_circ_0001739、lncRNA AC159540.1、FTO 和 MYC 的表达模式，并进行功能丧失和获得分析，以检查它们对 CRC 细胞生物学功能的影响。纯化 SW480 细胞来源的 Exos，然后进行体外研究以揭示 hsa_circ_0001739/lncRNA AC159540 的作用。

结果

在 CRC 组织和细胞中，miR-218-5p 下调，而 hsa_circ_0001739/lncRNA AC159540.1 上调。hsa_circ_0001739/lncRNA AC159540.1的沉默抑制了CRC细胞的恶性表型。Exos介导的hsa_circ_0001739/lncRNA AC159540.1竞争性抑制miR-218-5p以升高FTO和MYC。Exos介导的hsa_circ_0001739/lncRNA AC159540.1在CRC中的诱导作用也在体内得到验证。