Open AccessA miR-26a/E2F7 feedback loop contributes to tamoxifen resistance in ER-positive breast cancer
Author(s) -
Jian Liu,
Xiang Li,
Meng Wang,
Guodong Xiao,
Guolong Yang,
Huangzhen Wang,
Yanbo Li,
Xin Sun,
Sida Qin,
Ning Du,
Hong Ren,
Yamei Pang
Publication year - 2018
Publication title -
international journal of oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.405
H-Index - 122
ISSN - 1019-6439
DOI - 10.3892/ijo.2018.4492
Subject(s) - biology , cancer research , oncogene , breast cancer , microrna , gene silencing , downregulation and upregulation , gene knockdown , estrogen receptor , cancer , tamoxifen , cell cycle , gene , genetics
Tamoxifen (TAM) resistance is a substantial challenge in the treatment of estrogen receptor (ER)-positive breast cancer. Previous studies have revealed an important role of microRNA (miRNA/miR)-26a in TAM resistance in breast cancer. However, the mechanism underlying the regulatory effects of miR-26a on TAM resistance remains to be elucidated. The expression levels of miR-26a in ER-positive breast cancer were detected by reverse transcription-quantitative polymerase chain reaction. E2F transcription factor 7 (E2F7) and MYC proto-oncogene, bHLH transcription factor (MYC) levels were detected by western blotting. The present study demonstrated that miR-26a expression was reduced in ER-positive breast cancer compared with in normal breast tissues, whereas E2F7 expression was significantly elevated. Furthermore, an inverse correlation between miR-26a and E2F7 expression was detected in ER-positive breast cancer. The results indicated that miR-26a directly inhibited E2F7 expression through translational inhibition and indirectly inhibited MYC expression partly via E2F7 repression. E2F7, in turn, decreased miR-26a expression via MYC-induced transcriptional inhibition of miRNAs. Furthermore, transfection with miR-26a mimics increased the expression of its host genes (CTD small phosphatase like and CTD small phosphatase 2), whereas ectopic E2F7 expression abrogated the effects of miR-26a. These findings indicated that miR-26a and E2F7 may form a double-negative feedback loop, resulting in downregulation of miR-26a and upregulation of E2F7 in ER-positive breast cancer. Both miR-26a knockdown and E2F7 overexpression conferred resistance to TAM in MCF-7 cells. Conversely, miR-26a overexpression and E2F7 silencing resensitized MCF-7 resistant cells to TAM. These findings revealed that a feedback loop between miR-26a and E2F7 may promote TAM resistance in ER-positive breast cancer.