Effect of LINC00672 on sensitivity of breast cancer to tamoxifen and its related mechanisms
10.3760/cma.j.cn.115807-20210706-00210
- VernacularTitle:LINC00672对乳腺癌他莫昔芬敏感性的影响及机制探究
- Author:
Hongwei HU
1
;
Zhaochen XIN
;
Hongwei ZHANG
Author Information
1. 浙江省台州医院乳腺甲状腺外科 317000
- Keywords:
Breast cancer;
LINC00672;
Tamoxifen;
Chemotherapy resistance
- From:
Chinese Journal of Endocrine Surgery
2021;15(5):463-466
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of long non-coding RNA (LncRNA) LINC00672 on sensitivity of breast cancer to tamoxifen and related mechanisms.Methods:Human breast cancer MCF-7 cells was treated in vitro to establish tamoxifen resistance (resistance group) and corresponding parental cell line (parent group) . The interfered LINC00672 and control cell line were constructed by Crisper-cas9 in resistant cells. (Interference 1 group, interference 2 group and control group) . The expression of LINC00672, Akt and HER2 mRNA was determined by real-time quantitative PCR. The expression levels of total Akt (Akt-pan) , phosphorylation of Akt (p-Akt) and HER2 were detected by Western blot.CCK-8 assay was used to detect cell resistance to tamoxifen.Results:The expressions of LINC00672, Akt and HER2 mRNA in the parental group were (1.000±0.086) , (1.000±0.254) and (1.000±0.208) , and the TAM IC 50 was (1.417±0.153) μmol/L. The expressions of LINC00672, Akt and HER2 mRNA in the resistance group were (4.286±0.593) , (4.175±0.274) and (2.519±0.389) , and the TAM IC 50 was (12.029±1.016) μmol/L. The expressions of LINC00672, Akt and HER2 mRNA in the control group were (1.000±0.093) , (1.000±0.090) and (1.000±0.097) , and the TAM IC 50 was (10.58±0.639) μmol/L. The expressions of LINC00672, Akt and HER2 mRNA in the interference group 1 were (0.331±0.023) , (0.892±0.044) and (0.458±0.077) , and the TAM IC 50 was (6.250±0.836) μmol/L. The expressions of LINC00672, Akt and HER2 mRNA in the interference group 2 were (0.304±0.016) , (0.919±0.050) and (0.416±0.080) , and the TAM IC 50 was (4.764±0.553) μmol/L. As compared with the parental group, the expressions of LINC00672, Akt and HER2 mRNA were significantly up-regulated ( P<0.01) in resistance group, the protein levels of Akt-pan, p-Akt and HER2 was up-regulated. The IC 50 value of tamoxifen was significantly increased in resistance group ( P<0.01) . As compared with the control group, the expression levels of LINC00672 and HER2 mRNA were significantly decreased in the interference group 1 and the interference group 2 ( P<0.01) , the levels of Akt was not significantly changed ( P>0.05) . The protein levels of p-Akt and HER2 were significantly decreased but there was no significant change in the expression of Akt-pan. The IC50 value of tamoxifen was significantly decreased ( P<0.01) . Conclusion:LINC00672 may be involved in the formation of tamoxifen resistance in breast cancer cells, and its underlying mechanism is related to the promotion of HER2/p-Akt pathway.
