Roles of miR-4442 in Colorectal Cancer: Predicting Early Recurrence and Regulating Epithelial-Mesenchymal Transition

被引:5
作者
Shibamoto, Jun [1 ]
Arita, Tomohiro [1 ]
Konishi, Hirotaka [1 ]
Kataoka, Satoshi [1 ]
Furuke, Hirotaka [1 ]
Takaki, Wataru [1 ]
Kiuchi, Jun [1 ]
Shimizu, Hiroki [1 ]
Yamamoto, Yusuke [1 ]
Komatsu, Shuhei [1 ]
Shiozaki, Atsushi [1 ]
Kuriu, Yoshiaki [1 ]
Otsuji, Eigo [1 ]
机构
[1] Kyoto Prefectural Univ Med, Dept Surg, Div Digest Surg, 465 Kajii-cho, Kawaramachi Hirokoji, Kamigyo Ku, Kyoto 6028566, Japan
关键词
biomarker; colorectal cancer; epithelial-mesenchymal transition; microRNA; recurrence; EARLY RELAPSE; CURATIVE SURGERY; PROGNOSIS; MICRORNAS; PROGRESSION; INHIBITION; ANTIGEN; GROWTH;
D O I
10.3390/genes14071414
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Early recurrence in patients with colorectal cancer (CRC) is associated with a poor prognosis. We aimed to identify circulating microRNAs that are biomarkers of early CRC recurrence and elucidate their functions. We identified miR-4442 as a candidate biomarker by microRNA array analysis comparing preoperative and postoperative plasma levels in patients with CRC, with and without recurrence. The association between preoperative plasma miR-4442 levels, clinicopathological features, and recurrence-free survival was analyzed in 108 patients with CRC after curative surgery. Furthermore, cell-function analyses were performed, and the involvement of miR-4442 in regulating epithelial-mesenchymal transition (EMT) was examined. Preoperatively plasma miR-4442 levels were associated with CRC recurrence and exhibited an incremental increase with earlier recurrence dates. Moreover, miR-4442 demonstrated high sensitivity and specificity as a potential biomarker for early CRC recurrence. The expression of miR-4442 in cancer tissues of patients with metastatic liver cancer from CRC was higher than in normal liver, CRC, and normal colorectal tissues. The overexpression of miR-4442 promoted the proliferative, migratory, and invasive activities of CRC cells, decreased levels of RBMS1 and E-cadherin, and increased levels of N-cadherin and Snail1. Plasma miR-4442 is a clinically useful biomarker for predicting the early recurrence of CRC. Furthermore, miR-4442 regulates EMT in CRC by directly targeting the messenger RNA of RBMS1.
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页数:18
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