MicroRNA-195 Suppresses the Progression of Pancreatic Cancer by Targeting DCLK1
Background/Aims: Doublecortin-like kinase 1 (DCLK1) is emerging as a tumor-specific stem cell marker in pancreatic cancer (PC). MicroRNA-195 (miR-195) plays an important role in many types of tumors. However, the roles of DCLK1 in cancer and miRNAs that directly regulate DCLK1 have not been elucidat...
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2017-12-01
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| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | https://www.karger.com/Article/FullText/485876 |
| _version_ | 1818287425346076672 |
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| author | Bin Zhou Chuandong Sun Xiao Hu Hanxiang Zhan Hao Zou Yujie Feng Fabo Qiu Shun Zhang Liqun Wu Bingyuan Zhang |
| author_facet | Bin Zhou Chuandong Sun Xiao Hu Hanxiang Zhan Hao Zou Yujie Feng Fabo Qiu Shun Zhang Liqun Wu Bingyuan Zhang |
| author_sort | Bin Zhou |
| collection | DOAJ |
| description | Background/Aims: Doublecortin-like kinase 1 (DCLK1) is emerging as a tumor-specific stem cell marker in pancreatic cancer (PC). MicroRNA-195 (miR-195) plays an important role in many types of tumors. However, the roles of DCLK1 in cancer and miRNAs that directly regulate DCLK1 have not been elucidated. The goal of this study is to assess the effects of miR-195 on inhibiting DCLK1 and to clarify the regulating mechanism of miR-195-DCLK1 in PC cells. Methods: The expression of DCLK1 protein and miR-195 in PC tissues and adjacent healthy pancreatic tissues was detected by Western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR), respectively and the correlation between overall survival of PC patients and expression of DCLK1 was measured by Kaplan-Meier analysis. Bioinformatics tools were used to identify the target gene of miR-195. Effects of miR-195 and DCLK1 on proliferation and cell cycle of PC cells were analyzed by MTT, colony formation assays and flow cytometry. Transwell and wound-healing experiments were employed to examine the cellular migration and invasion. A xenograft mouse model was also used to test the effects of miR-195 on tumor growth and metastasis in vivo. Results: The expression level of DCLK1 and miR-195 shows an inverse correlation in PC tissues and cell lines. A higher DCLK1 level is associated with higher TNM (tumor, node, and metastasis) stage, higher rate of lymph node metastasis, and poor survival. Luciferase reporter assay shows that miR-195 directly targets DCLK1. Overexpression of miR-195 inhibits proliferation, migration and invasion of PC cells, whereas downregulation of miR-195 has an opposite role. These actions were similar to the effects of knockdown and overexpression of DCLK1, respectively. Conclusions: These data suggest that miR-195 has tumor suppressor roles in PC by targeting DCLK1. MiR-195-DCLK1 pathway may provide insight into PC progression and represent a novel, promising diagnostic and therapeutic target for PC. |
| first_indexed | 2024-12-13T01:40:17Z |
| format | Article |
| id | doaj.art-b94f797475f049c48801a0a428b2bcd8 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-13T01:40:17Z |
| publishDate | 2017-12-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-b94f797475f049c48801a0a428b2bcd82022-12-22T00:03:47ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782017-12-014451867188110.1159/000485876485876MicroRNA-195 Suppresses the Progression of Pancreatic Cancer by Targeting DCLK1Bin ZhouChuandong SunXiao HuHanxiang ZhanHao ZouYujie FengFabo QiuShun ZhangLiqun WuBingyuan ZhangBackground/Aims: Doublecortin-like kinase 1 (DCLK1) is emerging as a tumor-specific stem cell marker in pancreatic cancer (PC). MicroRNA-195 (miR-195) plays an important role in many types of tumors. However, the roles of DCLK1 in cancer and miRNAs that directly regulate DCLK1 have not been elucidated. The goal of this study is to assess the effects of miR-195 on inhibiting DCLK1 and to clarify the regulating mechanism of miR-195-DCLK1 in PC cells. Methods: The expression of DCLK1 protein and miR-195 in PC tissues and adjacent healthy pancreatic tissues was detected by Western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR), respectively and the correlation between overall survival of PC patients and expression of DCLK1 was measured by Kaplan-Meier analysis. Bioinformatics tools were used to identify the target gene of miR-195. Effects of miR-195 and DCLK1 on proliferation and cell cycle of PC cells were analyzed by MTT, colony formation assays and flow cytometry. Transwell and wound-healing experiments were employed to examine the cellular migration and invasion. A xenograft mouse model was also used to test the effects of miR-195 on tumor growth and metastasis in vivo. Results: The expression level of DCLK1 and miR-195 shows an inverse correlation in PC tissues and cell lines. A higher DCLK1 level is associated with higher TNM (tumor, node, and metastasis) stage, higher rate of lymph node metastasis, and poor survival. Luciferase reporter assay shows that miR-195 directly targets DCLK1. Overexpression of miR-195 inhibits proliferation, migration and invasion of PC cells, whereas downregulation of miR-195 has an opposite role. These actions were similar to the effects of knockdown and overexpression of DCLK1, respectively. Conclusions: These data suggest that miR-195 has tumor suppressor roles in PC by targeting DCLK1. MiR-195-DCLK1 pathway may provide insight into PC progression and represent a novel, promising diagnostic and therapeutic target for PC.https://www.karger.com/Article/FullText/485876Pancreatic cancerDCLK1MiR-195ProliferationMetastasis |
| spellingShingle | Bin Zhou Chuandong Sun Xiao Hu Hanxiang Zhan Hao Zou Yujie Feng Fabo Qiu Shun Zhang Liqun Wu Bingyuan Zhang MicroRNA-195 Suppresses the Progression of Pancreatic Cancer by Targeting DCLK1 Cellular Physiology and Biochemistry Pancreatic cancer DCLK1 MiR-195 Proliferation Metastasis |
| title | MicroRNA-195 Suppresses the Progression of Pancreatic Cancer by Targeting DCLK1 |
| title_full | MicroRNA-195 Suppresses the Progression of Pancreatic Cancer by Targeting DCLK1 |
| title_fullStr | MicroRNA-195 Suppresses the Progression of Pancreatic Cancer by Targeting DCLK1 |
| title_full_unstemmed | MicroRNA-195 Suppresses the Progression of Pancreatic Cancer by Targeting DCLK1 |
| title_short | MicroRNA-195 Suppresses the Progression of Pancreatic Cancer by Targeting DCLK1 |
| title_sort | microrna 195 suppresses the progression of pancreatic cancer by targeting dclk1 |
| topic | Pancreatic cancer DCLK1 MiR-195 Proliferation Metastasis |
| url | https://www.karger.com/Article/FullText/485876 |
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