Hypoxia‑regulated exosomal miR‑185 inhibits esophageal squamous cell carcinoma progression and predicts prognosis

Maiyulan,Abula; Matsumoto,Yasunori; Wang,Huan; Murakami,Kentaro; Toyozumi,Takeshi; Otsuka,Ryota; Shiraishi,Tadashi; Kinoshita,Kazuya; Hu,Jie; Iida,Shinichiro; Morishita,Hiroki; Makiyama,Tenshi; Nishioka,Yuri; Kano,Masayuki; Matsubara,Hisahiro

doi:10.3892/ol.2024.14467

Hypoxia‑regulated exosomal miR‑185 inhibits esophageal squamous cell carcinoma progression and predicts prognosis

Authors:
- Abula Maiyulan
- Yasunori Matsumoto
- Huan Wang
- Kentaro Murakami
- Takeshi Toyozumi
- Ryota Otsuka
- Tadashi Shiraishi
- Kazuya Kinoshita
- Jie Hu
- Shinichiro Iida
- Hiroki Morishita
- Tenshi Makiyama
- Yuri Nishioka
- Masayuki Kano
- Hisahiro Matsubara
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Affiliations: Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba 260‑8670, Japan
Published online on: May 22, 2024 https://doi.org/10.3892/ol.2024.14467
Article Number: 334
Copyright: © Maiyulan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Despite advances in treatment and diagnosis, the prognosis of patients with esophageal squamous cell carcinoma (ESCC) remains poor. MicroRNAs (miRNAs/miRs) are associated with prognosis in esophageal cancer, indicating that they may help guide treatment decisions. The aim of the present study was to explore exosomal miR‑185 as a candidate prognostic biomarker and therapeutic target in ESCC, to investigate its biological function and clinical significance, and to ascertain the applicability of circulating exosomal miR‑185 for the development of targeted drugs for ESCC treatment. A GeneChip miRNA array was used to compare exosomal miRNA expression in ESCC cell lines under hypoxia with those under normoxia. Exosomal miR‑185 expression was then confirmed by reverse transcription‑quantitative PCR. Patient background and prognosis were compared between high and low miR‑185 expression groups. Functional analyses were performed to evaluate the antitumor effects of miR‑185 in ESCC cells. Global Gene Set Enrichment Analysis of The Cancer Genome Atlas data was also performed, and differentially expressed exosomal miRNAs under hypoxia were identified compared to those under normoxia. Hypoxia markedly decreased the expression of exosomal miR‑185 in KYSE‑960 and T.Tn cell culture media. Overexpression of miR‑185 suppressed the migration, invasion and colony‑forming abilities of ESCC lines, and also suppressed cell cycle progression and promoted apoptosis after cisplatin treatment. Notably, high miR‑185 expression was associated with signaling pathways related to cell death, DNA damage and p53. Furthermore, circulating exosomal miR‑185 levels were associated with cN and cStage, and could predict progression‑free survival and disease‑specific survival of patients with ESCC after initial treatment. In conclusion, miR‑185 holds potential as a prognostic biomarker and therapeutic target in ESCC.

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