MicroRNA-338-5p reverses chemoresistance and inhibits invasion of esophageal squamous cell carcinoma cells by targeting Id-1

被引:43
作者
Han, Liang [1 ]
Cui, Di [1 ]
Li, Bin [1 ,8 ]
Xu, Wen Wen [1 ,9 ]
Lam, Alfred King Y. [2 ,3 ]
Chan, Kin Tak [4 ]
Zhu, Yun [1 ]
Lee, Nikki P. Y. [4 ]
Law, Simon Y. K. [4 ]
Guan, Xin Yuan [5 ]
Qin, Yan Ru [6 ]
Chan, Kwok Wah [7 ]
Ma, Stephanie [1 ]
Tsao, Sai Wah [1 ]
Cheung, Annie L. M. [1 ]
机构
[1] Univ Hong Kong, Sch Biomed Sci, Li Ka Shing Fac Med, Hong Kong, Peoples R China
[2] Griffith Med Sch, Dept Pathol, Gold Coast, Qld, Australia
[3] Menzies Hlth Inst Queensland, Gold Coast, Qld, Australia
[4] Univ Hong Kong, Dept Surg, Hong Kong, Peoples R China
[5] Univ Hong Kong, Li Ka Shing Fac Med, Dept Clin Oncol, Hong Kong, Peoples R China
[6] Zhengzhou Univ, Affiliated Hosp 1, Dept Clin Oncol, Zhengzhou, Henan, Peoples R China
[7] Univ Hong Kong, Li Ka Shing Fac Med, Dept Pathol, Hong Kong, Peoples R China
[8] Jinan Univ, Coll Life Sci & Technol, Guangzhou, Guangdong, Peoples R China
[9] Jinan Univ, Coll Pharm, Inst Tumor Pharmacol, Guangzhou, Guangdong, Peoples R China
关键词
chemoresistance; circulating miRNA; esophageal cancer; Id-1; miR-338-5p; GLIOBLASTOMA CELLS; CANCER-CELLS; GENES; METASTASIS; IDENTIFICATION; CHEMOTHERAPY; DEGRADATION; OXALIPLATIN; PROGRESSION; EXPRESSION;
D O I
10.1111/cas.14220
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
5-Fluorouracil (5-FU) is a chemotherapeutic agent commonly used to treat esophageal squamous cell carcinoma (ESCC), but acquisition of chemoresistance frequently occurs and the underlying mechanisms are not fully understood. We found that microRNA (miR)-338-5p was underexpressed in ESCC cells with acquired 5-FU chemoresistance. Forced expression of miR-338-5p in these cells resulted in downregulation of Id-1, and restoration of both in vitro and in vivo sensitivity to 5-FU treatment. The effects were abolished by reexpression of Id-1. In contrast, miR-338-5p knockdown induced 5-FU resistance in chemosensitive esophageal cell lines, and knockdown of both miR-338-5p and Id-1 resensitized the cells to 5-FU. In addition, miR-338-5p had suppressive effects on migration and invasion of ESCC cells. Luciferase reporter assay confirmed a direct interaction between miR-338-5p and the 3 '-UTR of Id-1. We also found that miR-338-5p was significantly downregulated in tumor tissue and serum samples of patients with ESCC. Notably, low serum miR-338-5p expression level was associated with poorer survival and poor response to 5-FU/cisplatin-based neoadjuvant chemoradiotherapy. In summary, we found that miR-338-5p can modulate 5-FU chemoresistance and inhibit invasion-related functions in ESCC by negatively regulating Id-1, and that serum miR-338-5p could be a novel noninvasive prognostic and predictive biomarker in ESCC.
引用
收藏
页码:3677 / 3688
页数:12
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