Insulin receptor substrate‑1 and dishevelled 2 are negatively regulated by microRNA‑144 and inhibit nasopharyngeal carcinoma cell malignancy

An,Xuemei; Jiang,Yunlan; Chen,Defeng; Chen,Jianjun

doi:10.3892/etm.2021.10738

Insulin receptor substrate‑1 and dishevelled 2 are negatively regulated by microRNA‑144 and inhibit nasopharyngeal carcinoma cell malignancy

Authors:
- Xuemei An
- Yunlan Jiang
- Defeng Chen
- Jianjun Chen
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Affiliations: Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 410000, P.R. China, Department of Ear, Nose and Throat, The First People's Hospital of Neijiang, Neijiang, Sichuan 641000, P.R. China
Published online on: September 16, 2021 https://doi.org/10.3892/etm.2021.10738
Article Number: 1303
Copyright: © An et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Insulin receptor substrate‑1 (IRS‑1) is reported to play a critical role in the development, progression, invasion and metastasis of several types of tumors and is abnormally expressed in nasopharyngeal carcinoma (NPC). Although IRS‑1 is predicted to be targeted by microRNA (miR)‑144, the biological roles and potential mechanisms of miR‑144 in NPC remain unclear. In the present study, the expression levels of miR‑144 and IRS‑1 in several NPC cell lines were first examined, and found that they were negatively correlated. Following the introduction of the miR‑144 mimic, IRS‑1 was downregulated at the protein level without affecting the mRNA level. The Cell Counting Kit‑8 assay showed that the miR‑144 mimic and siRNA targeting IRS‑1 mRNA significantly decreased cell proliferation by arresting the cell cycle at the G₁/G₀ phase. The malignant behaviours of NPC cell lines, including migration, invasion and tumour formation in soft agar, were then analyzed after regulating miR‑144 levels; as expected, the results showed that both the miR‑144 mimic and siIRS‑1 decreased these malignant behaviours. Furthermore, the downregulation of IRS‑1 by miR‑144 decreased the expression level of dishevelled 2 (Dvl2) protein without affecting its mRNA level, and Dvl2 overexpression abolished the inhibitory effect of the miR‑144 mimic in NPC, indicating that miR‑144 potentially regulates NPC by indirectly regulating Dvl2. Taken together, the present study results suggest that miR‑144 acts as a tumour suppressor in NPC cell lines by regulating IRS‑1 and Dvl2, which indicates that it is a potential therapeutic target for NPC treatment.

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