MicroRNA-21 promotes phosphatase gene and protein kinase B/ phosphatidylinositol 3-kinase expression in colorectal cancer

被引:22
作者
Sheng, Wei-Zhong [1 ]
Chen, Yu-Sheng [1 ]
Tu, Chuan-Tao [2 ]
He, Juan [2 ]
Zhang, Bo [1 ]
Gao, Wei-Dong [1 ]
机构
[1] Fudan Univ, Affiliated Zhongshan Hosp, Dept Gen Surg, 180 Fenglin Rd, Shanghai 200032, Peoples R China
[2] Fudan Univ, Affiliated Zhongshan Hosp, Dept Digest, Shanghai 200032, Peoples R China
关键词
MicroRNA-21; protein kinase B; Colorectal cancer; phosphatidylinositol; 3-kinase; phosphatase and tensin homolog; TUMOR-SUPPRESSOR; GASTRIC-CANCER; PI3K/PTEN/AKT PATHWAY; SIGNALING PATHWAY; THYROID-CANCER; PTEN; CELLS; RESISTANCE; MIR-21; CARCINOMA;
D O I
10.3748/wjg.v22.i24.5532
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
AIM: to explore the regulatory mechanism of the target gene of microRNA-21 (miR-21), phosphatase gene (PTEN), and its downstream proteins, protein kinase B (AKT) and phosphatidylinositol 3-kinase (PI3K), in colorectal cancer (CRC) cells. METHODS: Quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the expression levels of miR-21 and PTEN in HCT116, HT29, Colo32 and SW480 CRC cell lines. Also, the expression levels of PTEN mRNA and its downstream proteins AKT and PI3K in HCT116 cells after downregulating miR-21 were investigated. RESULTS: Comparing the miR-21 expression in CRC cells, the expression levels of miR-21 were highest in HCT116 cells, and the expression levels of miR-21 were lowest in SW480 cells. In comparing miR-21 and PTEN expression in CRC cells, we found that the protein expression levels of miR-21 and PTEN were inversely correlated (P < 0.05); when miR-21 expression was reduced, mRNA expression levels of PTEN did not significantly change (P > 0.05), but the expression levels of its protein significantly increased (P < 0.05). In comparing the levels of PTEN protein and downstream AKT and PI3K in HCT116 cells after downregulation of miR-21 expression, the levels of AKT and PI3K protein expression significantly decreased (P < 0.05). CONCLUSION: PTEN is one of the direct target genes of miR-21. Thus, phosphatase gene and its downstream AKT and PI3K expression levels can be regulated by regulating the expression levels of miR-21, which in turn regulates the development of CRC.
引用
收藏
页码:5532 / 5539
页数:8
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[11]   Activation of spinal phosphatidylinositol 3-kinase/protein kinase B mediates pain behavior induced by plantar incision in mice [J].
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[16]   Ceramide-1-phosphate promotes cell survival through activation of the phosphatidylinositol 3-kinase/protein kinase B pathway [J].
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Kong, JY ;
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Wang, SW ;
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González, M ;
Eivemark, S ;
Salh, B ;
Duronio, V ;
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[17]   Phosphatidylinositol 3-kinase could be a promising target in lung cancer therapy [J].
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[20]   Inositide signalling in Chlamydomonas:: characterization of a phosphatidylinositol 3-kinase gene [J].
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