MicroRNA-21 (Mir-21) Promotes Cell Growth and Invasion by Repressing Tumor Suppressor PTEN in Colorectal Cancer
Background/Aims: 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...
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2017-09-01
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| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | https://www.karger.com/Article/FullText/481648 |
| _version_ | 1818043290389315584 |
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| author | Yiying Wu Yi Song Yao Xiong Xiaodong Wang Ke Xu Bin Han Yang Bai Li Li Yuanyuan Zhang Liming Zhou |
| author_facet | Yiying Wu Yi Song Yao Xiong Xiaodong Wang Ke Xu Bin Han Yang Bai Li Li Yuanyuan Zhang Liming Zhou |
| author_sort | Yiying Wu |
| collection | DOAJ |
| description | Background/Aims: 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. Methods: 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. Results: 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). Conclusion: 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. |
| first_indexed | 2024-12-10T08:59:52Z |
| format | Article |
| id | doaj.art-a09c6b523d6a41ae9a776d71ee6ee7d9 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-10T08:59:52Z |
| publishDate | 2017-09-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-a09c6b523d6a41ae9a776d71ee6ee7d92022-12-22T01:55:18ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782017-09-0143394595810.1159/000481648481648MicroRNA-21 (Mir-21) Promotes Cell Growth and Invasion by Repressing Tumor Suppressor PTEN in Colorectal CancerYiying WuYi SongYao XiongXiaodong WangKe XuBin HanYang BaiLi LiYuanyuan ZhangLiming ZhouBackground/Aims: 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. Methods: 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. Results: 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). Conclusion: 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.https://www.karger.com/Article/FullText/481648Colorectal carcinomaMiR-21PTENProliferationInvasiveness |
| spellingShingle | Yiying Wu Yi Song Yao Xiong Xiaodong Wang Ke Xu Bin Han Yang Bai Li Li Yuanyuan Zhang Liming Zhou MicroRNA-21 (Mir-21) Promotes Cell Growth and Invasion by Repressing Tumor Suppressor PTEN in Colorectal Cancer Cellular Physiology and Biochemistry Colorectal carcinoma MiR-21 PTEN Proliferation Invasiveness |
| title | MicroRNA-21 (Mir-21) Promotes Cell Growth and Invasion by Repressing Tumor Suppressor PTEN in Colorectal Cancer |
| title_full | MicroRNA-21 (Mir-21) Promotes Cell Growth and Invasion by Repressing Tumor Suppressor PTEN in Colorectal Cancer |
| title_fullStr | MicroRNA-21 (Mir-21) Promotes Cell Growth and Invasion by Repressing Tumor Suppressor PTEN in Colorectal Cancer |
| title_full_unstemmed | MicroRNA-21 (Mir-21) Promotes Cell Growth and Invasion by Repressing Tumor Suppressor PTEN in Colorectal Cancer |
| title_short | MicroRNA-21 (Mir-21) Promotes Cell Growth and Invasion by Repressing Tumor Suppressor PTEN in Colorectal Cancer |
| title_sort | microrna 21 mir 21 promotes cell growth and invasion by repressing tumor suppressor pten in colorectal cancer |
| topic | Colorectal carcinoma MiR-21 PTEN Proliferation Invasiveness |
| url | https://www.karger.com/Article/FullText/481648 |
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