Exosome-mediated Let-7a inhibits malignant biological behaviors of triple-negative breast cancer cells by down-regulating MYC expression
10.3872/j.issn.1007-385x.2019.09.005
- VernacularTitle:外泌体介导的Let-7a通过下调MYC表达抑制三阴性乳腺癌细胞的恶性 生物学行为
- Author:
LI Feng
1
;
ZHANG Yan
2
;
ZHANG Qiong
1
;
TAO Jin
1
;
BAI Shutong
3
;
SONG Na
1
;
SUN Mingling
1
;
DUAN Yating
2
Author Information
1. Oncology Department, Chongqing Traditional Chinese Medicine Hospital
2. Gynaecology Department, Chongqing Traditional Chinese Medicine Hospital
3. Basic Laboratory, Chongqing Traditional Chinese Medicine Hospital
- Publication Type:Journal Article
- Keywords:
triple negative breast cancer (TNBC);
MDA-MB-231 cell;
exosome (EXO);
Let-7a;
MYC;
malignant biological behavior
- From:
Chinese Journal of Cancer Biotherapy
2019;26(9):962-968
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the role of exosome (EXO) transporting Let-7a to regulate MYC gene in the malignant biological behaviors of triple negative breast cancer (TNBC) cell, and to explore the underlying mechanism. Methods: After the completion of cell culture, the gene and protein expressions of MYC and Let-7a in TNBC MDA-MB-231cells were detected by qPCR and WB, respectively. Recombinant lenti-virus vector carrying Let-7a and Crisper/Cas-9 system with MYC knockdown were transfected into MDA-MB-231 cells; MTT assay, Transwell assay and Scratch healing assay were performed to examine the proliferation, invasion and migration of MDA-MB-231 cells. Luciferase activity assay was performed to validate the binding between MYC and Let-7a. EXO was isolated and identified by transmission electron microscopy and WB assay in wild-type and Let-7a over-expressed MDA-MB-231 cells, respectively. After co-incubation of two types of EXO and MDA-MB-231 cells, the effects of Let-7a on biological behaviors of MDAMB-231 cells via EXO were detected by qPCR, WB, MTT and Transwell etc. Results: Let-7a was negatively correlated with MYC in breast cancer tissues and cell lines (all P<0.05); MYC promoted while Let-7a inhibited the proliferation, migration and invasion of breast cancer cells (all P<0.01); Let-7a silenced MYC by acting on 3'UTR of MYC gene, thereby reducing the expression of MYC protein (P<0.05); Let-7a was enveloped by EXO and transported to cancer cells, there by inhibiting the proliferation, migration and invasion of MDA-MB-231 cells. Conclusion: EXO some mediated Let-7a silences MYC gene by acting on its 3'UTR region, thus inhibiting the proliferation, migration and invasion of MDA-MB-231 cells.
- Full text:20190905.pdf