Downregulation of microRNA‑494 inhibits cell proliferation in lung squamous cell carcinoma via the induction of PUMA‑α‑mediated apoptosis

Gao,Xinyuan; Yang,Xiaohua; He,Fengzhen; Liu,Xue; Liu,Ding; Yuan,Xiaomei

doi:10.3892/etm.2023.11941

Downregulation of microRNA‑494 inhibits cell proliferation in lung squamous cell carcinoma via the induction of PUMA‑α‑mediated apoptosis

Authors:
- Xinyuan Gao
- Xiaohua Yang
- Fengzhen He
- Xue Liu
- Ding Liu
- Xiaomei Yuan
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Affiliations: Department of Respiratory and Critical Care, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, P.R. China, Department of Oncology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, P.R. China
Published online on: April 11, 2023 https://doi.org/10.3892/etm.2023.11941
Article Number: 242
Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Increased evidence has shown that abnormal microRNA (miRNA) plays pivotal roles in numerous types of cancer. However, their expression, function and mechanism in lung squamous cell carcinoma (LSCC) remains to be fully elucidated. The aim of the present study was to investigate the suppressive role of miR‑494 in LSCC progression and elucidate its regulatory mechanism. By analyzing expression profiles of miRNAs in LSCC tissues using miRNA microarray, it was revealed that miR‑494 was significantly upregulated in 22 pairs of LSCC tissues. Subsequently, reverse transcription-quantitative PCR was performed to determine the expression of miR‑494 and p53‑upregulated‑modulator‑of‑apoptosis‑α (PUMA‑α). Western blot analysis was conducted to examine protein levels. Dual‑luciferase reporter assay was used to confirm the binding between miR‑494 and PUMA‑α. Annexin V‑fluoresceine isothiocyanate/propidium iodide staining and CCK‑8 assays were employed to determine cell apoptosis and cell viability, respectively. It was also revealed that miR‑494 was highly expressed in LSCC cell lines compared with that in 16HBE cells. Further experiments confirmed that knockdown of miR‑494 reduced cell viability and induced LSCC apoptosis. Bioinformatics analysis predicted that miR‑494 could potentially target PUMA‑α; also known as Bcl‑2‑binding component 3, a pro‑apoptotic factor, and an inverse correlation between the expression of miR‑494 and PUMA‑α mRNA levels in LSCC tissues was found. Furthermore, PUMA‑α inhibition could reverse the promoting effect of miR‑494 knockdown on apoptosis in LSCC cells. Taken together, these findings demonstrated that miR‑494 functions as an oncogene by targeting PUMA‑α in LSCC, and miR‑494 may serve as a novel therapeutic target for treating LSCC.

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