Upregulation of microRNA‑375 increases the cisplatin‑sensitivity of human gastric cancer cells by regulating ERBB2

Zhou,Ning; Qu,Yanli; Xu,Chunlei; Tang,Yong

doi:10.3892/etm.2015.2920

Upregulation of microRNA‑375 increases the cisplatin‑sensitivity of human gastric cancer cells by regulating ERBB2

Authors:
- Ning Zhou
- Yanli Qu
- Chunlei Xu
- Yong Tang
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Affiliations: Department of Digestive Internal Medicine, Xinjiang Medical University Affiliated Tumor Hospital, Urumqi, Xinjiang 830054, P.R. China
Published online on: December 8, 2015 https://doi.org/10.3892/etm.2015.2920
Pages: 625-630

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Abstract

Resistance to chemotherapy is a major challenge in the effective treatment of patients with gastric cancer; however, the mechanisms underlying chemoresistance in gastric cancer cells are yet to be elucidated. MicroRNAs (miRNAs) have previously been associated with cancer progression and sensitivity to chemotherapy; therefore, the present study aimed to identify miRNAs that may influence the sensitivity of human gastric cancer cells to cisplatin (DDP) treatment. Initially, miRNAs that were differentially expressed between the DDP‑sensitive SGC7901 human gastric cancer cell line and DDP‑resistant SGC7901/DDP cell line were identified using high‑throughput sequencing technology. miRNA‑375 (miR‑375), which was shown to be downregulated in the SGC7901/DDP cells, has previously been associated with numerous types of cancer; however, to the best of our knowledge, a role for miR‑375 in the DDP‑sensitivity of gastric cancer cells has yet to be explored. In the present study, the expression levels of miR‑375 were significantly downregulated in the SGC7901/DDP cells, as compared with the SGC7901 cells, as demonstrated by reverse transcription‑quantitative polymerase chain reaction. In addition, upregulation of miR‑375 significantly enhanced the anti‑proliferative and apoptosis‑inducing effects of DDP, whereas downregulation of miR‑375 decreased these effects. Subsequently, western blot analysis demonstrated that upregulation of miR‑375 in the SGC7901/DDP cells increased their sensitivity to DDP treatment via regulating the protein expression levels of erb‑b2 receptor tyrosine kinase 2 and phosphorylated‑Akt. The results of the present study indicate that the expression levels of miR‑375 may influence the sensitivity of human gastric cancer cells to the effects of DDP; thus suggesting that a combination of miR‑375 regulation and DDP may be considered a novel strategy in the treatment of patients with chemoresistant gastric cancer.

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