miRNA‑328 overexpression confers cisplatin resistance in non‑small cell lung cancer via targeting of PTEN

Wang,Chunmei; Wang,Shijun; Ma,Feng'e; Zhang,Weidan

doi:10.3892/mmr.2018.9478

miRNA‑328 overexpression confers cisplatin resistance in non‑small cell lung cancer via targeting of PTEN

Authors:
- Chunmei Wang
- Shijun Wang
- Feng'e Ma
- Weidan Zhang
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Affiliations: Department of Respiration, Dezhou People's Hospital, Dezhou, Shandong 253014, P.R. China, Department of Emergency, Dezhou People's Hospital, Dezhou, Shandong 253014, P.R. China, Department of Outpatients, Dezhou People's Hospital, Dezhou, Shandong 253014, P.R. China, Department of Intensive Medicine, Dezhou People's Hospital, Dezhou, Shandong 253014, P.R. China
Published online on: September 12, 2018 https://doi.org/10.3892/mmr.2018.9478
Pages: 4563-4570

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Abstract

Chemotherapy resistance, the molecular mechanism of which is complex and has not been fully understood, poses a major challenge in the treatment of patients with non‑small cell lung cancer (NSCLC). The dysregulation of microRNAs (miRs) has been reported to serve a pivotal role in the development of cancer and drug resistance. In the present study, reverse transcription‑quantitative polymerase chain reaction analysis revealed a significant increase in miR‑328 and a significant decrease in phosphatase and tensin homolog (PTEN) mRNA expression levels within tumor tissues from patients with cisplatin‑resistant NSCLC compared with those of cisplatin‑sensitive NSCLC patients. In addition, there was a negative correlation between PTEN mRNA and the miR‑328 expression levels. In addition, higher miR‑328 expression levels, and lower PTEN mRNA and protein expression levels, were detected in cisplatin‑resistant A549 (A549rCDDP) cells when compared with in their parental cells. A549rCDDP cells demonstrated significantly higher cell viability compared with A549 cells following treatment with all concentrations of cisplatin tested (2, 4, 6 and 8 µM). Additionally, transfection of miR‑328 inhibitor significantly increased PTEN mRNA and protein expression levels. Furthermore, the present study predicted and confirmed PTEN, a well‑known tumor suppressor, as a direct target of miR‑328 in NSCLC cells via the online tool MiRanda and a dual luciferase assay, respectively. Cell viability assay and flow cytometry analysis demonstrated that inhibition of miR‑328 also induced cellular apoptosis and decreased cell proliferation in A549rCDDP cells treated with cisplatin. In conclusion, these results suggested that abnormal expression of miR‑328 may contribute to cisplatin resistance in NSCLC, and may be considered to be a novel therapeutic target and indicator for the treatment and prognosis of patients with NSCLC treated with cisplatin‑based chemotherapy.

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