MiR-26a and miR-144 inhibit proliferation and metastasis of esophageal squamous cell cancer by inhibiting cyclooxygenase-2

miR-26a和miR-144通过抑制环氧合酶-2抑制食管鳞状细胞癌的增殖和转移

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作者:Ying Shao, Peng Li, Sheng-Tao Zhu, Ji-Ping Yue, Xiao-Jun Ji, Dan Ma, Li Wang, Yong-Jun Wang, Ye Zong, Yong-Dong Wu, Shu-Tian Zhang

Abstract

The altered expression of miRNAs is involved in carcinogenesis of esophageal squamous cell carcinoma (ESCC), but whether miRNAs regulate COX-2 expression in ESCC is not clear. To this end, the expression levels of miR-26a and miR-144 in ESCC clinical tissues and cell lines were investigated by qRT-PCR. COX-2 and PEG2 were quantified by western blot and ELISA. Decrease in miR-26a and miR-144 expression in ESCC was found by a comparison between 30 pairs of ESCC tumor and adjacent normal tissues as well as in 11 ESCC cell lines (P < 0.001). Co-transfection of miR-26a and miR-144 in ESCC cell lines more significantly suppressed cell proliferation, migration, and invasion than did either miR-26a or miR-144 alone (all P < 0.001), as shown by assays of CCK8, migration and invasion and flow cytometry. The inhibitory effect of these two miRNAs in vivo was also verified in nude mice xenograft models. COX-2 was confirmed as a target of miR-26a and miR-144. In conclusion, miR-26a and miR-144 expression is downregulated in ESCC. Co-expression of miR-26a and miR-144 in ESCC cells resulted in inhibition of proliferation and metastasis in vitro and in vivo, suggesting that targeting COX-2 may be the mechanism of these two miRNAs.

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