POU2F1 inhibits miR-29b1/a cluster-mediated suppression of PIK3R1 and PIK3R3 expression to regulate gastric cancer cell invasion and migration

被引:0
作者
Xiao, Yizhi [1 ,2 ]
Yang, Ping [1 ]
Xiao, Wushuang [1 ]
Yu, Zhen [1 ]
Li, Jiaying [1 ]
Li, Xiaofeng [2 ]
Lin, Jianjiao [3 ]
Zhang, Jieming [1 ]
Pei, Miaomiao [1 ]
Hong, Linjie [1 ]
Yang, Juanying [1 ]
Lin, Zhizhao [1 ]
Jiang, Ping [1 ]
Xiang, Li [3 ]
Li, Guoxin [4 ]
Ai, Xinbo [5 ]
Dai, Weiyu [1 ,6 ]
Tang, Weimei [1 ]
Wang, Jide [1 ,3 ]
机构
[1] Southern Med Univ, Nanfang Hosp, Dept Gastroenterol, Guangdong Prov Key Lab Gastroenterol, Guangzhou 510515, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Affiliated Hosp 5, Dept Gastroenterol, Zhuhai 519000, Guangdong, Peoples R China
[3] Chinese Univ Hong Kong, Shenzhen & Longgang Dist Peoples Hosp Shenzhen, Sch Med, Dept Affiliated Hosp 2, Shenzhen 518172, Guangdong, Peoples R China
[4] Southern Med Univ, Nanfang Hosp, Dept Gen Surg, Guangzhou 510515, Guangdong, Peoples R China
[5] Jinan Univ, Zhuhai Peoples Hosp, Zhuhai Clin Med Coll, Dept Gastroenterol, Zhuhai 519000, Guangdong, Peoples R China
[6] Southern Med Univ, Guangdong Prov Peoples Hosp, Guangdong Acad Med Sci, Dept Gastroenterol, Guangzhou 510080, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
Gastric cancer; miR-29b-3p; miR-29a-3p; Metastasis; HEPATOCELLULAR-CARCINOMA; TUMOR-SUPPRESSOR; PROMOTES; PROLIFERATION; METASTASIS; FAMILY; VS-5584; NETWORK; TARGET; GROWTH;
D O I
10.1097/CM9.0000000000003181
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background:The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown.Methods:Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3 '-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice.Results:POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo. Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p, and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p, miR-29a-3p, PIK3R1, and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1, PIK3R1, and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples.Conclusions:The POU2F1-miR-29b-3p/miR-29a-3p-PIK3R1/PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.
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页码:838 / 850
页数:13
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