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The current study aimed to explore the potential function of miR\u2010375\u20103p in 5\u2010fluorouracil (5\u2010FU) resistance. MicroRNA\u2010375\u20103p was found to be widely downregulated in human CRC cell lines and tissues and to promote the sensitivity of CRC cells to 5\u2010FU by inducing colon cancer cell apoptosis and cycle arrest and by inhibiting cell growth, migration, and invasion in vitro. Thymidylate synthase (TYMS) was found to be a direct target of miR\u2010375\u20103p, and TYMS knockdown exerted similar effects as miR\u2010375\u20103p overexpression on the CRC cellular response to 5\u2010FU. Lipid\u2010coated calcium carbonate nanoparticles (NPs) were designed to cotransport 5\u2010FU and miR\u2010375\u20103p into cells efficiently and rapidly and to release the drugs in a weakly acidic tumor microenvironment. The therapeutic effect of combined miR\u2010375\u00a0+\u00a05\u2010FU\/NPs was significantly higher than that of the individual treatments in mouse s.c. xenografts derived from HCT116 cells. Our results suggest that restoring miR\u2010375\u20103p levels could be a future novel therapeutic strategy to enhance chemosensitivity to 5\u2010FU.<\/jats:p>","DOI":"10.1111\/cas.14356","type":"journal-article","created":{"date-parts":[[2020,2,19]],"date-time":"2020-02-19T14:42:28Z","timestamp":1582123348000},"page":"1528-1541","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":86,"title":["MicroRNA\u2010375\u20103p enhances chemosensitivity to 5\u2010fluorouracil by targeting thymidylate synthase in colorectal cancer"],"prefix":"10.1111","volume":"111","author":[{"given":"Fei","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Zhongnan Hospital of Wuhan University Wuhan China"},{"name":"Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases Wuhan 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