肿瘤细胞衍生的细胞外囊泡将 miR-3129 转移至靶基因 TXNIP 以促进肝癌转移。

Tumor cells derived-extracellular vesicles transfer miR-3129 to promote hepatocellular carcinoma metastasis by targeting TXNIP.

机构信息

Department of Hepatic Surgery VI, Third Affiliated Hospital of Second Military Medical University, Shanghai, 200438, China.

Department of Hepatic Surgery VI, Third Affiliated Hospital of Second Military Medical University, Shanghai, 200438, China; Tongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.

出版信息

Dig Liver Dis. 2021 Apr;53(4):474-485. doi: 10.1016/j.dld.2021.01.003. Epub 2021 Feb 6.

DOI:10.1016/j.dld.2021.01.003

PMID:33563583

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is the most predominant primary liver cancer. Extracellular vesicles (EV)-mediated microRNA (miRNA) delivery is critical in cancer metastasis. We aimed to identify the mechanism of HCC cell-derived EVs-mediated miR-3129 in HCC.

METHODS

After EVs isolation and identification, miR-3129 expression in plasma EVs was evaluated and its diagnostic efficiency was analyzed. miR-3129 inhibitor was transfected into HepG2 and SMMC7721 cells, and cell malignant episodes were assessed. HCC cells were incubated with EVs from MHCC-97H cells and transfected with miR-3129 inhibitor and/or TXNIP. The nude mice were injected with MHCC-97H cells-EV or MHCC-97H cells-EV/miR-3129 inhibitor, and HCC growth and metastasis were assessed.

RESULTS

miR-3129 was highly expressed in plasma EVs from HCC patients, which was the essential diagnostic biomarker for HCC. miR-3129 downregulation inhibited the malignant episodes of HCC cells. MHCC-97H cell-EVs were absorbed by HCC cells and transferred miR-3129 to HCC cells. EVs-carried miR-3129 promoted malignant episodes of HCC cells, which were weakened by miR-3129 inhibition in EVs. miR-3129 targeted TXNIP. TXNIP overexpression averted the effect of EVs-carried miR-3129 in HCC. In vivo, MHCC-97H cell-EVs transferred miR-3129 to facilitate HCC growth and metastasis.

CONCLUSION

MHCC-97H cell-EVs transferred miR-3129 to promote HCC metastasis by targeting TXNIP.

摘要

背景

肝细胞癌（HCC）是最主要的原发性肝癌。细胞外囊泡（EV）介导的 microRNA（miRNA）传递在癌症转移中至关重要。我们旨在确定 HCC 细胞衍生 EV 介导的 miR-3129 在 HCC 中的作用机制。

方法

在分离和鉴定 EV 后，评估了血浆 EVs 中 miR-3129 的表达，并分析了其诊断效率。将 miR-3129 抑制剂转染到 HepG2 和 SMMC7721 细胞中，评估细胞恶性事件。将 HCC 细胞与来自 MHCC-97H 细胞的 EV 孵育，并转染 miR-3129 抑制剂和/或 TXNIP。将裸鼠注射 MHCC-97H 细胞-EV 或 MHCC-97H 细胞-EV/miR-3129 抑制剂，并评估 HCC 生长和转移。

结果

HCC 患者血浆 EVs 中 miR-3129 表达水平较高，是 HCC 的重要诊断生物标志物。miR-3129 下调抑制了 HCC 细胞的恶性事件。MHCC-97H 细胞-EVs 被 HCC 细胞吸收，并将 miR-3129 转移至 HCC 细胞。EV 携带的 miR-3129 促进了 HCC 细胞的恶性事件，而 EV 携带的 miR-3129 抑制则削弱了这一作用。miR-3129 靶向 TXNIP。TXNIP 过表达可阻止 EV 携带的 miR-3129 在 HCC 中的作用。在体内，MHCC-97H 细胞-EVs 将 miR-3129 转移至促进 HCC 生长和转移。