外泌体 MALAT1 通过海绵吸附 miR-26a/26b 促进结直肠癌细胞侵袭转移及其机制研究

Exosomal MALAT1 sponges miR-26a/26b to promote the invasion and metastasis of colorectal cancer via FUT4 enhanced fucosylation and PI3K/Akt pathway.

机构信息

College of Laboratory Medicine, Dalian Medical University, 9 Lushunnan Road Xiduan, Dalian, 116044, Liaoning Province, China.

Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116027, Liaoning Province, China.

出版信息

J Exp Clin Cancer Res. 2020 Mar 24;39(1):54. doi: 10.1186/s13046-020-01562-6.

BACKGROUND

Exosomes are vesicles of endocytic origin released by various cell types and emerging as important mediators in tumor cells. Human metastases-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA known to promote cell proliferation, metastasis, and invasion in colorectal cancer (CRC).

METHODS

The expression of MALAT1 was analyzed in CRC using qRT-PCR. FUT4 and fucosylation levels were detected in CRC clinical samples and CRC cell lines by immunofluorescent staining, western blot and lectin blot analysis. CRC derived exosomes were isolated and used to examine their tumor-promoting effects in vitro and in vivo.

RESULTS

The invasive and metastatic abilities of primary CRC cells were enhanced after exposure to exosomes derived from highly metastatic CRC cells, which increased the fucosyltransferase 4 (FUT4) levels and fucosylation not by directly transmitting FUT4 mRNA. Exosomal MALAT1 increased FUT4 expresssion via sponging miR-26a/26b. Furthermore, MALAT1/miR-26a/26b/FUT4 axis played an important role in exosome-mediated CRC progression. Exosomal MALAT1 also mediated FUT4-associated fucosylation and activated the PI3K/AKT/mTOR pathway.

CONCLUSIONS

These data indicated that exosomal MALAT1 promoted the malignant behavior of CRC cells by sponging miR-26a/26b via regulating FUT4 and activating PI3K/Akt/mTOR pathway.

背景

外泌体是由各种细胞类型释放的内体起源的囊泡，作为肿瘤细胞中重要的介质而出现。人类转移相关肺腺癌转录物 1（MALAT1）是一种长非编码 RNA，已知可促进结直肠癌（CRC）中的细胞增殖、转移和侵袭。

方法

使用 qRT-PCR 分析 CRC 中 MALAT1 的表达。通过免疫荧光染色、western blot 和凝集素印迹分析检测 CRC 临床样本和 CRC 细胞系中的 FUT4 和岩藻糖基化水平。分离 CRC 衍生的外泌体，并用于体外和体内研究其促进肿瘤的作用。

结果

与高转移性 CRC 细胞来源的外泌体孵育后，原发性 CRC 细胞的侵袭和转移能力增强，这增加了岩藻糖基转移酶 4（FUT4）水平和岩藻糖基化，而不是通过直接传递 FUT4 mRNA。外泌体 MALAT1 通过海绵 miR-26a/26b 增加 FUT4 表达。此外，MALAT1/miR-26a/26b/FUT4 轴在外泌体介导的 CRC 进展中起重要作用。外泌体 MALAT1 还介导 FUT4 相关的岩藻糖基化并激活 PI3K/AKT/mTOR 途径。