10.6084/M9.FIGSHARE.16413439.V1
Lili Ren
Lili
Ren
Huanhuan Zhou
Huanhuan
Zhou
Lei Lei
Lei
Lei
Yongjun Zhang
Yongjun
Zhang
Hu Cai
Hu
Cai
Xiaojia Wang
Xiaojia
Wang
Long non-coding RNA FOXD3 antisense RNA 1 augments anti-estrogen resistance in breast cancer cells through the microRNA-363/ trefoil factor 1/ phosphatidylinositol 3-kinase/protein kinase B axis
<p>Long non-coding RNA (lncRNA) FOXD3 antisense RNA 1 (FOXD3-AS1) has been reported to participate in multiple processes that contribute toward the development of cancer. The present study aimed to explore the effect of lncRNA FOXD3-AS1 on anti-estrogen resistance in breast cancer (BC) cells. FOXD3-AS1 was found to be highly expressed in BC cell lines. Moreover, FOXD3-AS1 was highly expressed in estrogen receptor-negative (ER<sup>−</sup>) cells compared to the ER-positive (ER<sup>+</sup>) cells. FOXD3-AS1 overexpression in T47D and MCF-7 (ER<sup>+</sup>) cells enhanced the resistance of cells to tamoxifen (TMX), whereas FOX3-AS1 downregulation reduced the TMX resistance in MDA-MB-231 (ER<sup>−</sup>) cells. Similar results were reproduced <i>in vivo</i> that FOXD3-AS1 inhibition reduced the growth of xenograft tumors formed by MDA-MB-231 cells following TMX treatment whereas FOXD3-AS1 overexpression in T47D cells facilitated tumor growth. The bioinformatic analysis and luciferase assays indicated that FOXD3-AS1 sponged microRNA-363 (miR-363) to restore expression of trefoil factor 1 (TFF1) mRNA. Overexpression of miR-363 reduced T47D cell proliferation induced by FOXD3-AS1, whereas overexpression of TFF1 restored growth of MDA-MB-231 cells reduced after FOXD3-AS1 silencing. The phosphorylation of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) was increased by FOXD3-AS1 but attenuated by miR-363. Inhibition of PI3K/Akt blocked the role of FOXD3-AS1 and reduced the TMX resistance in T47D and MCF-7 cells. Taken together, the present study suggested that FOXD3-AS1 sponges miR-363 to upregulate TFF1 expression, leading to PI3K/Akt signaling activation and anti-estrogen resistance in BC cells.</p>
Biochemistry
Cell Biology
Molecular Biology
Physiology
Pharmacology
Biological Sciences not elsewhere classified
Developmental Biology
Cancer
Hematology
Taylor & Francis
2021
2021-08-23
2024-02-12
Journal contribution
1194627 Bytes
10.6084/m9.figshare.16413439
10.1080/21655979.2021.1962694
CC BY 4.0