MiRNA-206 suppresses PGE2-induced colorectal cancer cell proliferation, migration, and invasion by targetting TM4SF1

被引:56
作者
Park, Young Ran [1 ,2 ]
Seo, Seung Young [1 ,2 ]
Kim, Se Lim [1 ,2 ]
Zhu, Shi Mao [1 ,2 ]
Chun, Sungkun [3 ]
Oh, Jung-Mi [3 ]
Lee, Min Ro [4 ]
Kim, Seong Hun [1 ,2 ]
Kim, In Hee [1 ,2 ]
Lee, Seung Ok [1 ,2 ]
Lee, Soo Teik [1 ,2 ]
Kim, Sang Wook [1 ,2 ]
机构
[1] Chonbuk Natl Univ, Chonbuk Natl Univ Hosp, Med Sch, Dept Internal Med, Jeonju, South Korea
[2] Chonbuk Natl Univ, Chonbuk Natl Univ Hosp, Med Sch, Res Inst Clin Med,Biomed Res Inst, Jeonju, South Korea
[3] Chonbuk Natl Univ, Med Sch, Dept Physiol, Jeonju, South Korea
[4] Chonbuk Natl Univ, Chonbuk Natl Univ Hosp, Dept Surg, Med Sch, Jeonju, South Korea
基金
新加坡国家研究基金会;
关键词
TUMOR-ASSOCIATED ANTIGEN-L6; BREAST-CANCER; DOWN-REGULATION; LUNG-CANCER; MIR-206; EXPRESSION; PATHWAY; MICRORNA-206; GROWTH; PROGRESSION;
D O I
10.1042/BSR20180664
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
MiRNA (miR)-206 plays a tumor suppressor role in various cancer types. Here, we investigated whether miR-206 is involved in prostaglandin E2 (PGE2)-induced epithelial-mesenchymal transition (EMT) in colorectal cancer (CRC) cells through the tar-getting of transmembrane 4 L six family member 1 (TM4SF1). The effect of PGE2 on growth and apoptosis of CRC cells was evaluated using the MTT assay and flow cytometry analysis, respectively. TM4SF1 and miR-206 expression levels were determined with quantitative polymerase chain reaction (qRT-PCR) in CRC tissues and cell lines. The concentration of PGE2 in the serum of CRC patients and healthy controls was measured with an ELISA kit. A miR-206 or TM4SF1 construct was transfected into cells with PGE2. Transwell migration and invasion assays were used to examine cell migration and invasion properties. Additionally, a luciferase assay was performed to determine whether TM4SF1 was directly targetted by miR-206. We found that miR-206 was down-regulated and TM4SF1 was up-regulated in human CRC tissues and cell lines. Moreover, miR-206 was negatively correlated with TM4SF1 expression. Bioinformatics analysis and a luciferase reporter assay revealed that miR-206 directly targetted the 3'-untranslated region (UTR) of TM4SF1, and TM4SF1 expression was reduced by miR-206 overexpression at both the mRNA and protein levels. Additionally, PGE2 significantly suppressed the expression of miR-206 and increased the expression of TM4SF1 in CRC cells. PGE2 induction led to enhanced CRC cell proliferation, migration, and invasion. Moreover, the overexpression of miR-206 decreased CRC cell proliferation, migration, and invasion compared with control group in PGE2-induced cells, and these effects could be recovered by the overexpression of TM4SF1. Overexpression of miR-206 also suppressed the expression of beta-catenin, VEGF, MMP-9, Snail, and Vimentin and enhanced E-cadherin expression in PGE2-induced cells. These results could be reversed by the overexpression of TM4SF1. At last, up-regulation of miR-206 suppressed expression of p-AKT and p-ERK by targetting TM4SF1 in PGE2-induced cells. Our results provide further evidence that miR-206 has a protective effect on PGE2-induced colon carcinogenesis.
引用
收藏
页码:1 / 15
页数:15
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