Low levels of tumour suppressor miR-655 in plasma contribute to lymphatic progression and poor outcomes in oesophageal squamous cell carcinoma

Jun Kiuchi†,
Shuhei Komatsu†Email author,
Taisuke Imamura,
Keiji Nishibeppu,
Katsutoshi Shoda,
Tomohiro Arita,
Toshiyuki Kosuga,
Hirotaka Konishi,
Atsushi Shiozaki,
Kazuma Okamoto,
Hitoshi Fujiwara,
Daisuke Ichikawa and
Eigo Otsuji

†Contributed equally

Molecular Cancer201918:2

https://doi.org/10.1186/s12943-018-0929-3

Received: 16 July 2018
Accepted: 26 December 2018
Published: 4 January 2019

Abstract

Recent studies identified that low levels of tumour suppressor microRNAs (miRNAs) in plasma/serum relate to tumour progression and poor outcomes in cancers. We selected six candidates (miR-126, 133b, 143, 203, 338-3p, 655) of tumour suppressor miRNAs in oesophageal squamous cell carcinoma (ESCC) by a systematic review of NCBI database. Of these, miR-655 levels were significantly down-regulated in plasma of ESCC patients compared to healthy volunteers by test- and validation-scale analyses. Low levels of plasma miR-655 were significantly associated with lymphatic invasion, lymph node metastasis and advanced stage. Univariate and multivariate analysis revealed that the low level of plasma miR-655 was an independent risk factor of lymphatic progression and a poor prognostic factor. Overexpression of miR-655 in ESCC cells inhibited cell proliferation, migration, invasion and epithelial-mesenchymal transition. Increased plasma miR-655 levels by the subcutaneous injection significantly inhibited lymph node metastasis in mice. Low levels of miR-655 in plasma relate to lymphatic progression and poor outcomes, and the restoration of the plasma miR-655 levels might inhibit tumour and lymphatic progression in ESCC.