Open Access

lncRNA GAS5 inhibits malignant progression by regulating macroautophagy and forms a negative feedback regulatory loop with the miR‑34a/mTOR/SIRT1 pathway in colorectal cancer

  • Authors:
    • Hao‑Gang Zhang
    • Fu‑Jing Wang
    • Yao Wang
    • Zi‑Xing Zhao
    • Peng‑Fei Qiao
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  • Published online on: October 26, 2020     https://doi.org/10.3892/or.2020.7825
  • Pages: 202-216
  • Copyright: © Zhang 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 growth arrest specific 5 (GAS5) exerts inhibitory effects through the modulation of several target microRNAs (miRs) in cancer. However, its potential roles and underlying relationship during colorectal cancer (CRC) progression are unclear. Therefore, we explored the role of the negative feedback loop formed by the GAS5/miR‑34a axis and mammalian target of rapamycin/sirtuin 1 (mTOR/SIRT1) pathway on macroautophagy and apoptosis in CRC. Expression of GAS5, miR‑34a, SIRT1 and mTOR in CRC patients and cell lines was detected by quantitative reverse transcription polymerase chain reaction. Online bioinformatic analysis was used to predict the downstream miRs of GAS5. Luciferase assay and western blotting were performed to demonstrate miR‑34a as a downstream target gene of GAS5 in CRC cells. The effects of the GAS5/miR‑34a axis on apoptosis, macroautophagy, and the mTOR/SIRT1 pathway were assessed by flow cytometry, transmission electron microscopy and western blotting, respectively. Our results suggested that GAS5 was downregulated and acted as a molecular sponge of miR‑34a during CRC progression. miR‑34a participated in regulating GAS5‑suppressed CRC cell macroautophagy and induced apoptosis through the mTOR/SIRT1 pathway. GAS5‑mediated macroautophagy was maintained in an equilibrium state that might have a protective effect on CRC cell apoptosis. The mTOR signaling pathway suppressed GAS5 expression and formed a negative regulation feedback loop with miR‑34a in CRC cells. Our results suggested that the GAS5/miR‑34a/SIRT1/mTOR negative regulatory feedback loop mediated CRC cell macroautophagy, and maintained the cells in an autonomous equilibrium state, but not excessive activation state, which functions as a strong antiapoptotic phenotype during human CRC progression.
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January-2021
Volume 45 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Copy and paste a formatted citation
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Spandidos Publications style
Zhang HG, Wang FJ, Wang Y, Zhao ZX and Qiao PF: lncRNA GAS5 inhibits malignant progression by regulating macroautophagy and forms a negative feedback regulatory loop with the miR‑34a/mTOR/SIRT1 pathway in colorectal cancer. Oncol Rep 45: 202-216, 2021.
APA
Zhang, H., Wang, F., Wang, Y., Zhao, Z., & Qiao, P. (2021). lncRNA GAS5 inhibits malignant progression by regulating macroautophagy and forms a negative feedback regulatory loop with the miR‑34a/mTOR/SIRT1 pathway in colorectal cancer. Oncology Reports, 45, 202-216. https://doi.org/10.3892/or.2020.7825
MLA
Zhang, H., Wang, F., Wang, Y., Zhao, Z., Qiao, P."lncRNA GAS5 inhibits malignant progression by regulating macroautophagy and forms a negative feedback regulatory loop with the miR‑34a/mTOR/SIRT1 pathway in colorectal cancer". Oncology Reports 45.1 (2021): 202-216.
Chicago
Zhang, H., Wang, F., Wang, Y., Zhao, Z., Qiao, P."lncRNA GAS5 inhibits malignant progression by regulating macroautophagy and forms a negative feedback regulatory loop with the miR‑34a/mTOR/SIRT1 pathway in colorectal cancer". Oncology Reports 45, no. 1 (2021): 202-216. https://doi.org/10.3892/or.2020.7825