Proliferation, apoptosis and invasion of human lung cancer cells are associated with NFATc1

Ren,Fenghai; Zhu,Kaibin; Wang,Yanbo; Zhou,Fucheng; Pang,Sainan; Chen,Lantao

doi:10.3892/etm.2022.11748

Proliferation, apoptosis and invasion of human lung cancer cells are associated with NFATc1

Authors:
- Fenghai Ren
- Kaibin Zhu
- Yanbo Wang
- Fucheng Zhou
- Sainan Pang
- Lantao Chen
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Affiliations: Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China
Published online on: December 6, 2022 https://doi.org/10.3892/etm.2022.11748
Article Number: 49
Copyright: © Ren et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The expression of nuclear factor of activated T cells c1 (NFATc1) is closely associated with the progression of numerous types of cancer. When NFATc1 expression becomes dysregulated in some types of cancer, this alteration can promote malignant transformation and thereby progression of cancer. NFATc1 expression has been demonstrated to be upregulated in lung cancer cells. This suggests that knockdown of NFATc1 in lung cancer cells may be a therapeutic marker for the treatment of cancer. In the present study, the effects of NFATc1 on the proliferation, apoptosis, invasion and migration of NCI‑H1299 and A549 lung cancer cell lines were explored. Lentivirus infection was used to establish a cell model of NFATc1 knockdown in A549 and NCI‑H1299 lung cancer cells. Reverse transcription‑quantitative PCR was subsequently performed to detect NFATc1 expression in these human lung cancer cells. MTT, wound healing, colony formation and Transwell invasion assays, and flow cytometry were then performed to measure the proliferation, invasion, apoptosis and cell cycle of the cells. Finally, western blot analysis was performed to investigate the mechanism underlying the involvement of NFATc1 in these processes. NFATc1 knockdown was found to significantly inhibit the proliferation, clone formation, migration and invasion of the cells. Furthermore, the cell cycle was arrested at the G₁ phase and the expression levels of the target proteins located downstream in the signaling pathway, namely CDK4, c‑Myc, ERK, p38 and N‑cadherin, were decreased. Following NFATc1 knockdown, the percentages of apoptotic cells were increased, and the expression levels of Bax, cleaved caspase‑3 and E‑cadherin were also increased. Taken together, the results of the present study suggested that NFATc1 serves an oncogenic role in lung cancer. In terms of the underlying mechanism, NFATc1 promoted the proliferation of lung cancer cells by inhibiting the MAPK and epithelial‑to‑mesenchymal transition signaling pathways, suggesting that NFATc1 may be a novel target for therapeutic intervention for the treatment of lung cancer.

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