Long non‑coding RNA H19 mediates N‑acetyltransferase 1 gene methylation in the development of tamoxifen resistance in breast cancer

Sun,Hong; Wang,Guo; Cai,Jiaqin; Wei,Xiaoxia; Zeng,Ying; Peng,Yan; Zhuang,Jie

doi:10.3892/etm.2021.10934

Long non‑coding RNA H19 mediates N‑acetyltransferase 1 gene methylation in the development of tamoxifen resistance in breast cancer

Authors:
- Hong Sun
- Guo Wang
- Jiaqin Cai
- Xiaoxia Wei
- Ying Zeng
- Yan Peng
- Jie Zhuang
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Affiliations: Department of Pharmacy, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, Fujian 350001, P.R. China, Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan 410078, P.R. China
Published online on: October 28, 2021 https://doi.org/10.3892/etm.2021.10934
Article Number: 12
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Long non‑coding RNA (lncRNA) H19 is associated with proliferation, invasion and metastasis in numerous types of cancer. H19 lncRNA has been demonstrated to be an estrogen‑inducible gene, the expression of which is significantly increased in tamoxifen (TAM)‑resistant MCF‑7 breast cancer cells. The aim of the present study was to investigate the role and molecular mechanism of lncRNA H19 in the development of TAM resistance. TAM‑resistant MCF‑7 (MCF‑7R) cells were developed by the treatment of wild‑type MCF‑7 cells with 4‑hydroxytamoxifen. Analysis of H19 expression in the cells indicated that upregulation of H19 contributed to the resistance of the MCF‑7R cell line. Furthermore, when H19 was knocked down in the MCF‑7R cells, the sensitivity to 4‑hydroxytamoxifen was markedly restored. The results further demonstrated that N‑acetyltransferase 1 (NAT1) may serve an important role in TAM‑resistant cells, as NAT1 expression was notably downregulated in the MCF‑7R cells but significantly elevated following the knockdown of H19. In addition, lower expression of NAT1 and higher expression of H19 were indicated to be associated with poor prognosis in patients with breast cancer treated with TAM. The results of bisulfite genomic sequencing PCR analysis indicated that the methylation rate of NAT1 in MCF‑7R cells was significantly higher compared with that in MCF‑7 cells, while the methylation rate of NAT1 in TAM‑resistant cells transfected with small interfering RNA against H19 was significantly lower than that in the corresponding untransfected cells. Therefore, the present study suggests that the H19 gene regulates NAT1 expression in TAM‑resistant cells via the mediation of NAT1 promoter methylation.

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