CircRNA_0000392 promotes colorectal cancer progression through the miR-193a-5p/PIK3R3/AKT axis
Abstract Background Circular RNAs (circRNAs), important members of the noncoding RNA family, have been recently revealed to play a role in the pathogenic progression of diseases, particularly in the malignant progression of cancer. With the application of high-throughput sequencing technology, a lar...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-12-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13046-020-01799-1 |
| _version_ | 1828946721796784128 |
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| author | Hanchen Xu Yujing Liu Peiqiu Cheng Chunyan Wang Yang Liu Wenjun Zhou Yangxian Xu Guang Ji |
| author_facet | Hanchen Xu Yujing Liu Peiqiu Cheng Chunyan Wang Yang Liu Wenjun Zhou Yangxian Xu Guang Ji |
| author_sort | Hanchen Xu |
| collection | DOAJ |
| description | Abstract Background Circular RNAs (circRNAs), important members of the noncoding RNA family, have been recently revealed to play a role in the pathogenic progression of diseases, particularly in the malignant progression of cancer. With the application of high-throughput sequencing technology, a large number of circRNAs have been identified in tumor tissues, and some circRNAs have been demonstrated to act as oncogenes. In this study, we analyzed the circRNA expression profile in colorectal cancer (CRC) tissues and normal adjacent tissues by high-throughput sequencing. We focused on circRNA_0000392, a circRNA with significantly increased expression in CRCtissues, and further investigated its function in the progression of colorectal cancer. Methods The expression profile of circRNAs in 6 pairs of CRC tissues and normal adjacent tissues was analyzed by RNA sequencing. We verified the identified differentially expressed circRNAs in additional samples by qRT-PCR and selected circRNA_0000392 to evaluate its associations with clinicopathological features. Then, we knocked down circRNA_0000392 in CRC cells and investigated the in vitro and in vivo effects using functional experiments. Dual luciferase and RNA pull-down assays were performed to further explore the downstream potential molecular mechanisms. Results CircRNA_0000392 was significantly upregulated in CRC compared with normal adjacent tissues and cell lines. The expression level of circRNA_0000392 was positively correlated with the malignant progression of CRC. Functional studies revealed that reducing the expression of circRNA_0000392 could inhibit the proliferation and invasion of CRC both in vitro and in vivo. Mechanistically, circRNA_0000392 could act as a sponge of miR-193a-5p and regulate the expression of PIK3R3, affecting the activation of the AKT-mTOR pathway in CRC cells. Conclusions CircRNA_0000392 functions as an oncogene through the miR-193a-5p/PIK3R3/Akt axis in CRC cells, suggesting that circRNA_0000392 is a potential therapeutic target for the treatment of colorectal cancer and a predictive marker for CRC patients. |
| first_indexed | 2024-12-14T05:15:14Z |
| format | Article |
| id | doaj.art-788d5bd9e2c94517af7bcb4a6075be65 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-14T05:15:14Z |
| publishDate | 2020-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-788d5bd9e2c94517af7bcb4a6075be652022-12-21T23:15:50ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662020-12-0139111710.1186/s13046-020-01799-1CircRNA_0000392 promotes colorectal cancer progression through the miR-193a-5p/PIK3R3/AKT axisHanchen Xu0Yujing Liu1Peiqiu Cheng2Chunyan Wang3Yang Liu4Wenjun Zhou5Yangxian Xu6Guang Ji7Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese MedicineInstitute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese MedicineInstitute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese MedicineInstitute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese MedicineDepartment of General Surgery, Longhua Hospital, Shanghai University of Traditional Chinese MedicineInstitute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese MedicineDepartment of General Surgery, Longhua Hospital, Shanghai University of Traditional Chinese MedicineInstitute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese MedicineAbstract Background Circular RNAs (circRNAs), important members of the noncoding RNA family, have been recently revealed to play a role in the pathogenic progression of diseases, particularly in the malignant progression of cancer. With the application of high-throughput sequencing technology, a large number of circRNAs have been identified in tumor tissues, and some circRNAs have been demonstrated to act as oncogenes. In this study, we analyzed the circRNA expression profile in colorectal cancer (CRC) tissues and normal adjacent tissues by high-throughput sequencing. We focused on circRNA_0000392, a circRNA with significantly increased expression in CRCtissues, and further investigated its function in the progression of colorectal cancer. Methods The expression profile of circRNAs in 6 pairs of CRC tissues and normal adjacent tissues was analyzed by RNA sequencing. We verified the identified differentially expressed circRNAs in additional samples by qRT-PCR and selected circRNA_0000392 to evaluate its associations with clinicopathological features. Then, we knocked down circRNA_0000392 in CRC cells and investigated the in vitro and in vivo effects using functional experiments. Dual luciferase and RNA pull-down assays were performed to further explore the downstream potential molecular mechanisms. Results CircRNA_0000392 was significantly upregulated in CRC compared with normal adjacent tissues and cell lines. The expression level of circRNA_0000392 was positively correlated with the malignant progression of CRC. Functional studies revealed that reducing the expression of circRNA_0000392 could inhibit the proliferation and invasion of CRC both in vitro and in vivo. Mechanistically, circRNA_0000392 could act as a sponge of miR-193a-5p and regulate the expression of PIK3R3, affecting the activation of the AKT-mTOR pathway in CRC cells. Conclusions CircRNA_0000392 functions as an oncogene through the miR-193a-5p/PIK3R3/Akt axis in CRC cells, suggesting that circRNA_0000392 is a potential therapeutic target for the treatment of colorectal cancer and a predictive marker for CRC patients.https://doi.org/10.1186/s13046-020-01799-1Colorectal cancerCircular RNAs (circRNAs)RNA sequencingCircRNA_0000392miR-193a-5pPIK3R3 |
| spellingShingle | Hanchen Xu Yujing Liu Peiqiu Cheng Chunyan Wang Yang Liu Wenjun Zhou Yangxian Xu Guang Ji CircRNA_0000392 promotes colorectal cancer progression through the miR-193a-5p/PIK3R3/AKT axis Journal of Experimental & Clinical Cancer Research Colorectal cancer Circular RNAs (circRNAs) RNA sequencing CircRNA_0000392 miR-193a-5p PIK3R3 |
| title | CircRNA_0000392 promotes colorectal cancer progression through the miR-193a-5p/PIK3R3/AKT axis |
| title_full | CircRNA_0000392 promotes colorectal cancer progression through the miR-193a-5p/PIK3R3/AKT axis |
| title_fullStr | CircRNA_0000392 promotes colorectal cancer progression through the miR-193a-5p/PIK3R3/AKT axis |
| title_full_unstemmed | CircRNA_0000392 promotes colorectal cancer progression through the miR-193a-5p/PIK3R3/AKT axis |
| title_short | CircRNA_0000392 promotes colorectal cancer progression through the miR-193a-5p/PIK3R3/AKT axis |
| title_sort | circrna 0000392 promotes colorectal cancer progression through the mir 193a 5p pik3r3 akt axis |
| topic | Colorectal cancer Circular RNAs (circRNAs) RNA sequencing CircRNA_0000392 miR-193a-5p PIK3R3 |
| url | https://doi.org/10.1186/s13046-020-01799-1 |
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