Long non‑coding RNA growth arrest‑specific 5 (GAS5) acts as a tumor suppressor by promoting autophagy in breast cancer

Li,Guangping; Qian,Lin; Tang,Xiaoqin; Chen,Yuan; Zhao,Ziyi; Zhang,Cuiwei

doi:10.3892/mmr.2020.11334

Long non‑coding RNA growth arrest‑specific 5 (GAS5) acts as a tumor suppressor by promoting autophagy in breast cancer

Authors:
- Guangping Li
- Lin Qian
- Xiaoqin Tang
- Yuan Chen
- Ziyi Zhao
- Cuiwei Zhang
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Affiliations: Integration of Traditional and Western Medicine and Oncology, Chengdu, Sichuan 610072, P.R. China, The Teaching Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, P.R. China, Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
Published online on: July 10, 2020 https://doi.org/10.3892/mmr.2020.11334
Pages: 2460-2468
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Growth arrest‑specific 5 (GAS5) is a known tumor suppressor which negatively regulates cell survival and malignancy in several cancer cell types. The present study aimed to establish the correlation between GAS5 and unc‑51 like autophagy activating kinase (ULK)1/2, two key regulators of autophagy initiation in breast cancer (BC). To address this, expression levels of these genes were quantitively analyzed in BC clinical samples by performing reverse transcription‑quantitative PCR. GAS5 was downregulated in BC clinical samples compared with adjacent samples and was positively correlated with ULK1/2. Detection methods including cell cycle analysis, annexin V‑FITC/PI double staining and flow cytometry analysis, Transwell cell invasion assay, transfection and western blotting were used for BC cells. In MCF‑7 cells, it was also observed that overexpression of GAS5 upregulated ULK1/2 protein levels without disturbing other autophagy initiation‑associated proteins and inhibited cell proliferation, invasion and tumor formation. These effects were reversed by blocking autophagy with 3‑methyladenine (3‑MA). These results demonstrated that the suppressive effects of overexpressed GAS5 were mediated via autophagy induction, at least in part. Overexpression of GAS5 induced chemoresistance to cisplatin, which was not reversed by 3‑MA‑mediated inhibition of autophagy, indicating that GAS5 promotes chemosensitivity in an autophagy‑independent manner. Collectively, these results indicated that GAS5 contributes to the pathogenesis of BC potentially by promoting autophagy. However, the mechanism by which GAS5 functions as a tumor suppressor in an autophagy‑independent manner remains unknown.

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