Knockdown of lncRNA‑HOTAIR downregulates the drug‑resistance of breast cancer cells to doxorubicin via the PI3K/AKT/mTOR signaling pathway

Li,Zhixiang; Qian,Jun; Li,Jing; Zhu,Chao

doi:10.3892/etm.2019.7629

Knockdown of lncRNA‑HOTAIR downregulates the drug‑resistance of breast cancer cells to doxorubicin via the PI3K/AKT/mTOR signaling pathway

Authors:
- Zhixiang Li
- Jun Qian
- Jing Li
- Chao Zhu
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Affiliations: Department of Tumor Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233000, P.R. China
Published online on: May 29, 2019 https://doi.org/10.3892/etm.2019.7629
Pages: 435-442
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The resistance to chemotherapeutic drugs is a critical feature of breast cancer recurrence and metastasis. Long non‑coding RNAs (LncRNAs) serve key roles in tumor drug resistance. LncRNA‑HOX transcript antisense RNA (HOTAIR) has been reported to be overexpressed in certain types of cancer and may be closely associated with tumor resistance. The current study aimed to investigate the role of lncRNA‑HOTAIR in the regulation of breast cancer resistance to doxorubicin (DOX). A breast cancer cell line (MCF‑7) and DOX‑resistant breast cancer cell line (DOXR‑MCF‑7) were utilized in the current study. DOXR‑MCF‑7 cells were transfected with lncRNA‑HOTAIR small interfering RNA (siRNA) and control siRNA. Subsequently, MTT and colony formation assays were performed to assess cell proliferation. Cell apoptosis was also evaluated via flow cytometry. In addition, western blotting and reverse transcription‑quantitative polymerase chain reaction were performed to detect the expression of caspase‑3, B‑cell lymphoma 2, Bcl‑2‑associated X protein, phosphoinositide 3‑kinase (PI3K), protein kinase B (AKT) and mechanistic target of rapamycin (mTOR), and the phosphorylation of PI3K, AKT, and mTOR. The data indicated that lncRNA‑HOTAIR silencing decreased cell proliferation and increased apoptosis in MCF‑7 and DOXR MCF‑7 cells. Furthermore, lncRNA‑HOTAIR silencing significantly decreased the phosphorylation of PI3K, AKT and mTOR, indicating that the knockdown of lncRNA‑HOTAIR effectively attenuates the resistance of breast cancer cells to DOX by inhibiting the PI3K/AKT/mTOR pathway. In summary, the present study indicated that the knockdown of lncRNA‑HOTAIR weakened the resistance of breast cancer cells to DOX via PI3K/AKT/mTOR signaling, suggesting that lncRNA‑HOTAIR may be a novel intervention target to reverse DOX‑resistance in breast cancer.

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