MicroRNA-21 (Mir-21) Promotes Cell Growth and Invasion by Repressing Tumor Suppressor PTEN in Colorectal Cancer.

MicroRNA-21 (miR-21) has been demonstrated to play an important role in carcinogenesis; however, its mechanism of action in colorectal cancer (CRC) has not been fully elucidated. The aim of the present study was to explore the oncogenic function of miR-21 and its molecular mechanism in CRC. A total of 105 paired tumor and tumor-adjacent normal tissue specimens from CRC patients and two CRC cell lines (HCT-116 and SW480) were studied. The protein and mRNA expression levels of PTEN and miR-21 were examined using western blot analysis and real-time reverse transcription-PCR (qRT-PCR). Furthermore, we transfected CRC cells with different combinations of ectopic-expression vector or shRNA expression vector of miR-21 and phosphatase and tensin homolog (PTEN) to modulate the expression levels of miR-21 and PTEN respectively, and then analyzed the phenotypic alterations of CRC cells. Tumorigenesis was also evaluated by xenografting HCT-116 cells into nude mice. In this study, we showed that miR-21 expression was significantly up-regulated in CRC compared to that in normal tissues. Patients with advanced Tumor-Node-Metastasis (TNM) stage, lymph node metastasis, local invasion and higher serum carcinoembryonic antigen (CEA) levels displayed significantly high expression of miR-21. The PTEN protein level in CRC tissues and cells was inversely correlated with miR-21 expression. Furthermore, the transfection of CRC cells with pre-miR-21 could inhibit apoptosis and promote cellular proliferation, invasion, cell cycle progression and growth of xenografts in nude mice, whereas the transfection of miR-21-specific shRNA resulted in the opposite phenomena. In addition, silencing or elevating PTEN protein could partially reverse the effect of miR-21-specific shRNA or pre-miR-21 on apoptosis, cell cycle distribution, and invasion of CRC cells. Moreover, over-expression or knockdown of miR-21 altered the protein expression of PTEN and phosphorylated Akt (p-AKT). miR-21 can modulate the malignant phenotypes such as proliferation, anti-apoptosis, cell cycle progression and invasion of CRC cells by down-regulating PTEN protein expression. The results of study might improve our understanding of the regulatory mechanism of miR-21 and provide useful targets and approaches for the clinical diagnosis and therapy of CRC.

Wu Y ，Song Y ，Xiong Y ，Wang X ，Xu K ，Han B ，Bai Y ，Li L ，Zhang Y ，Zhou L ... -  《-》

MiR-21 regulates biological behavior through the PTEN/PI-3 K/Akt signaling pathway in human colorectal cancer cells.

Xiong B ，Cheng Y ，Ma L ，Zhang C ... -  《-》

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

Sheng WZ ，Chen YS ，Tu CT ，He J ，Zhang B ，Gao WD ... -  《-》

MicroRNA-92a functions as an oncogene in colorectal cancer by targeting PTEN.

Zhang G ，Zhou H ，Xiao H ，Liu Z ，Tian H ，Zhou T ... -  《-》

MicroRNA-106b promotes pituitary tumor cell proliferation and invasion through PI3K/AKT signaling pathway by targeting PTEN.

Zhou K ，Zhang T ，Fan Y ，Serick ，Du G ，Wu P ，Geng D ... -  《-》