miR-19b-3p promotes colon cancer proliferation and oxaliplatin-based chemoresistance by targeting SMAD4: validation by bioinformatics and experimental analyses
Abstract Background As a disease with extremely complex molecular mechanisms, many deregulated miRNAs have been identified in colon cancer. Few studies have been performed by using Ingenuity Pathways Analysis (IPA) to predict miRNAs specifically expressed in colon cancer. Methods A characteristic mi...
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| Format: | Article |
| Language: | English |
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BMC
2017-09-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
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| Online Access: | http://link.springer.com/article/10.1186/s13046-017-0602-5 |
| _version_ | 1818262202682966016 |
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| author | Tao Jiang Ling Ye Zhongbo Han Yuan Liu Yinxue Yang Zhihai Peng Junwei Fan |
| author_facet | Tao Jiang Ling Ye Zhongbo Han Yuan Liu Yinxue Yang Zhihai Peng Junwei Fan |
| author_sort | Tao Jiang |
| collection | DOAJ |
| description | Abstract Background As a disease with extremely complex molecular mechanisms, many deregulated miRNAs have been identified in colon cancer. Few studies have been performed by using Ingenuity Pathways Analysis (IPA) to predict miRNAs specifically expressed in colon cancer. Methods A characteristic microRNA-target network of colon cancer was explored using IPA. Then the clinical significance of miR-19b-3p was evaluated in 211 colon cancer patients. The roles of miR-19b-3p and its candidate target gene, SMAD4, in colon cancer progression were examined both in vitro and in vivo. Results Bioinformatics analysis showed that 15 microRNAs screened by IPA were significantly correlated with malignant biological behaviors of colon cancer. miR-19b-3p was the most significantly upregulated candidate based on the validation experiment using 211 colon cancer samples. High expression of miR-19b-3p was significantly associated with high N stage (P < 0.001), high AJCC stage (P < 0.001), poor histologic grade (P = 0.032), frequent venous and lymphatic invasion (P = 0.027), and liver metastasis (P < 0.001). Survival analysis revealed that miR-19b-3p was an independent prognostic factor associated with colon cancer patient’s overall survival (OS) and disease-free survival (DFS). miR-19b-3p promoted proliferation and chemoresistance of colon cancer cells, but had no effect on invasion in vitro, along with tumorigenesis in vivo. In addition, we confirmed that miR-19b-3p mediates resistance to oxaliplatin-based chemotherapy via SMAD4. Conclusions Our findings demonstrate the role of miR-19b-3p-SMAD4 axis in colon cancer progression, which may become a potential therapeutic target against chemotherapy resistance. |
| first_indexed | 2024-12-12T18:59:23Z |
| format | Article |
| id | doaj.art-a612dda195bd4cdba3f8344831c236ed |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-12T18:59:23Z |
| publishDate | 2017-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-a612dda195bd4cdba3f8344831c236ed2022-12-22T00:15:08ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662017-09-0136111410.1186/s13046-017-0602-5miR-19b-3p promotes colon cancer proliferation and oxaliplatin-based chemoresistance by targeting SMAD4: validation by bioinformatics and experimental analysesTao Jiang0Ling Ye1Zhongbo Han2Yuan Liu3Yinxue Yang4Zhihai Peng5Junwei Fan6Department of Anal-Colorectal Surgery, General Hospital of Ningxia Medical UniversityDepartment of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineDepartment of General Surgery, Central Hospital of Zi BoDepartment of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Anal-Colorectal Surgery, General Hospital of Ningxia Medical UniversityDepartment of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineDepartment of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineAbstract Background As a disease with extremely complex molecular mechanisms, many deregulated miRNAs have been identified in colon cancer. Few studies have been performed by using Ingenuity Pathways Analysis (IPA) to predict miRNAs specifically expressed in colon cancer. Methods A characteristic microRNA-target network of colon cancer was explored using IPA. Then the clinical significance of miR-19b-3p was evaluated in 211 colon cancer patients. The roles of miR-19b-3p and its candidate target gene, SMAD4, in colon cancer progression were examined both in vitro and in vivo. Results Bioinformatics analysis showed that 15 microRNAs screened by IPA were significantly correlated with malignant biological behaviors of colon cancer. miR-19b-3p was the most significantly upregulated candidate based on the validation experiment using 211 colon cancer samples. High expression of miR-19b-3p was significantly associated with high N stage (P < 0.001), high AJCC stage (P < 0.001), poor histologic grade (P = 0.032), frequent venous and lymphatic invasion (P = 0.027), and liver metastasis (P < 0.001). Survival analysis revealed that miR-19b-3p was an independent prognostic factor associated with colon cancer patient’s overall survival (OS) and disease-free survival (DFS). miR-19b-3p promoted proliferation and chemoresistance of colon cancer cells, but had no effect on invasion in vitro, along with tumorigenesis in vivo. In addition, we confirmed that miR-19b-3p mediates resistance to oxaliplatin-based chemotherapy via SMAD4. Conclusions Our findings demonstrate the role of miR-19b-3p-SMAD4 axis in colon cancer progression, which may become a potential therapeutic target against chemotherapy resistance.http://link.springer.com/article/10.1186/s13046-017-0602-5miR-19b-3pSMAD4ProliferationOxaliplatinChemoresistance |
| spellingShingle | Tao Jiang Ling Ye Zhongbo Han Yuan Liu Yinxue Yang Zhihai Peng Junwei Fan miR-19b-3p promotes colon cancer proliferation and oxaliplatin-based chemoresistance by targeting SMAD4: validation by bioinformatics and experimental analyses Journal of Experimental & Clinical Cancer Research miR-19b-3p SMAD4 Proliferation Oxaliplatin Chemoresistance |
| title | miR-19b-3p promotes colon cancer proliferation and oxaliplatin-based chemoresistance by targeting SMAD4: validation by bioinformatics and experimental analyses |
| title_full | miR-19b-3p promotes colon cancer proliferation and oxaliplatin-based chemoresistance by targeting SMAD4: validation by bioinformatics and experimental analyses |
| title_fullStr | miR-19b-3p promotes colon cancer proliferation and oxaliplatin-based chemoresistance by targeting SMAD4: validation by bioinformatics and experimental analyses |
| title_full_unstemmed | miR-19b-3p promotes colon cancer proliferation and oxaliplatin-based chemoresistance by targeting SMAD4: validation by bioinformatics and experimental analyses |
| title_short | miR-19b-3p promotes colon cancer proliferation and oxaliplatin-based chemoresistance by targeting SMAD4: validation by bioinformatics and experimental analyses |
| title_sort | mir 19b 3p promotes colon cancer proliferation and oxaliplatin based chemoresistance by targeting smad4 validation by bioinformatics and experimental analyses |
| topic | miR-19b-3p SMAD4 Proliferation Oxaliplatin Chemoresistance |
| url | http://link.springer.com/article/10.1186/s13046-017-0602-5 |
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