Long noncoding RNA FOXD2-AS1 incuced gastric cancer cell MGC-803 to apatinib resistance by regulating miR-185-5p/CCND2 modulating axis
10.3872/j.issn.1007-385x.2018.11.004
- VernacularTitle:lncRNA FOXD2-AS1通过调控miR-185-5p/CCND2分子轴诱导胃癌细 胞MGC-803对阿帕替尼的耐药性
- Author:
WU Xiaoxia1
1
,
2
;
SHAN Yongfeng
1
,
2
;
CAO Fei1
1
,
2
;
ZHANG Binbin1
1
,
2
;
WANG Haonan1
1
,
2
;
LIU Hui
1
,
2
;
XU Yan2
2
,
3
;
YU Hao1
1
,
2
Author Information
1. .Department of Oncology, the Fifth People'
2. s Hospital of Wuxi City
3. Department of Oncology, the second People'
- Publication Type:Journal Article
- Keywords:
gastric cancer;
MGC-803 cell;
MGC-803/APcell;
lncRNAFOXD2-AS1;
miR-185-5p;
CCND2;
apatinib
- From:
Chinese Journal of Cancer Biotherapy
2018;25(11):1104-1112
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the molecular mechanism of lncRNA FOXD2-AS1 participating in apatinib resistance in gastric cancer cells by regulating miR-185-5p/CCND2 axis. Methods: The gastri cancer tissues and corresponding paracancerous tissues of 25 patients with gastric cancer were collected from April 2016 to December 2017 in the Fifth People’s Hospital of Wuxi City. The expressions of FOXD2-AS1, miR-185-5p, and cyclin D2 (CCND2) in gastric cancer tissues or cell lines were examined by quantitative realtime polymerase chain reaction (qRT-PCR). CCK-8 assay, Transwell assay and Annexin V-FITC/PI double staining flow cytometry assay were applied to assess the sensitivity of gastric cancer cells to apatinib. The interaction between FOXD2-AS1, miR-185-5p and CCND2 was explored by dual luciferase reporter gene assay, which was then confirmed by qRT-PCR, and Western blotting. Results: FOXD2-AS1 was highly expressed in gastric cancer tissues and apatinib-resistant gastric cancer cells. Over-expression of FOXD2-AS1 promoted apatinib-resistance of MGC-803/AP cells. Dual luciferase reporter gene assay confirmed that FOXD2-AS1 directly interacted with miR-185-5p and suppressed its expression. miR-185-5p significantly abolished the promotion effect of FOXD2-AS1 on apatinibresistance via inhibiting cell proliferation, invasion and promoting apoptosis of gastric MGC-803/AP cells. miR-185-5p could negatively regulate CCND2 expression; and FOXD2-AS1 promoted the cell proliferation, invasion and inhibited apoptosis of MGC-803/AP cells via down-regulating the inhibition effect of miR-185-5p on CCND2, thus further enhanced the apatinib-resistance of gastric cancer cells. Conclusion: FOXD2-AS1 induced apatinib-resistance of gastric cancer cells by regulating miR-185-5p/CCND2 axis.
- Full text:20181104.pdf
