Post-transcriptional Gene Regulation in Colitis Associated Cancer
Colitis-associated cancer (CAC) has been linked to microRNA (miRNA) aberrant expression elicited by inflammation. In this study, we used the AOM/DSS-induced CAC mice model to explore the ectopic expression of miRNAs in the precancerous stage of CAC. As a result, we found that miR-31-5p, miR-223-3p,...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-06-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fgene.2019.00585/full |
| _version_ | 1811337640340881408 |
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| author | Gang Chen Gang Chen Yuan Feng Xuezheng Li Zhe Jiang Bei Bei Lin Zhang Yueqing Han Yanwu Li Ning Li Ning Li |
| author_facet | Gang Chen Gang Chen Yuan Feng Xuezheng Li Zhe Jiang Bei Bei Lin Zhang Yueqing Han Yanwu Li Ning Li Ning Li |
| author_sort | Gang Chen |
| collection | DOAJ |
| description | Colitis-associated cancer (CAC) has been linked to microRNA (miRNA) aberrant expression elicited by inflammation. In this study, we used the AOM/DSS-induced CAC mice model to explore the ectopic expression of miRNAs in the precancerous stage of CAC. As a result, we found that miR-31-5p, miR-223-3p, and let-7f-5p were dysregulated during the development of intestinal dysplasia. Subsequently, we first identified the role of these three miRNAs in CAC. Adenomatous polyposis coli (APC) was revealed as a new target of miR-223-3p, and solute carrier family 9- subfamily A-member 9 (SLC9A9) and APC membrane recruitment protein 3 (AMER3) were suggested as two new targets for let-7f-5p. For miR-31-5p, we proved that it can target LATS2 mRNA so as to modulate Hippo pathway in Caco2 cells. Second, to examine if targeting these three miRNAs would lead to CAC prevention, pedunculoside, a natural triterpene glycoside capable of rescuing the down-regulation of LATS2 and APC caused by either miR-31-5p or miR-223-3p overexpression, respectively, was used in the in vivo AOM/DSS-induced CAC model. The results showed that pedunculoside (25 mg/kg) substantially mitigated the damage to mice intestine caused by DSS/AOM. These results suggested that miRNAs-elicited post-transcriptional regulation is involved in the pathogenesis of CAC, and CAC can be prevented through targeting key miRNAs that are ectopically expressed in CAC. |
| first_indexed | 2024-04-13T17:57:47Z |
| format | Article |
| id | doaj.art-47229e1cfc8e490fbe70503be04b36d6 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-13T17:57:47Z |
| publishDate | 2019-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-47229e1cfc8e490fbe70503be04b36d62022-12-22T02:36:23ZengFrontiers Media S.A.Frontiers in Genetics1664-80212019-06-011010.3389/fgene.2019.00585452964Post-transcriptional Gene Regulation in Colitis Associated CancerGang Chen0Gang Chen1Yuan Feng2Xuezheng Li3Zhe Jiang4Bei Bei5Lin Zhang6Yueqing Han7Yanwu Li8Ning Li9Ning Li10School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, ChinaBeijing Key Laboratory of Bio-characteristic Profiling for Evaluation of Rational Drug Use, Beijing Shijitan Hospital, Capital Medical University, Beijing, ChinaSchool of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, ChinaDepartment of Pharmacy, Yanbian University Hospital, Yanji, ChinaDepartment of Pharmacy, Yanbian University Hospital, Yanji, ChinaSchool of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, ChinaSchool of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, ChinaSchool of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, ChinaPi-Wei Institute, Guangzhou University of Chinese Medicine, Guangzhou, ChinaSchool of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, ChinaBeijing Key Laboratory of Bio-characteristic Profiling for Evaluation of Rational Drug Use, Beijing Shijitan Hospital, Capital Medical University, Beijing, ChinaColitis-associated cancer (CAC) has been linked to microRNA (miRNA) aberrant expression elicited by inflammation. In this study, we used the AOM/DSS-induced CAC mice model to explore the ectopic expression of miRNAs in the precancerous stage of CAC. As a result, we found that miR-31-5p, miR-223-3p, and let-7f-5p were dysregulated during the development of intestinal dysplasia. Subsequently, we first identified the role of these three miRNAs in CAC. Adenomatous polyposis coli (APC) was revealed as a new target of miR-223-3p, and solute carrier family 9- subfamily A-member 9 (SLC9A9) and APC membrane recruitment protein 3 (AMER3) were suggested as two new targets for let-7f-5p. For miR-31-5p, we proved that it can target LATS2 mRNA so as to modulate Hippo pathway in Caco2 cells. Second, to examine if targeting these three miRNAs would lead to CAC prevention, pedunculoside, a natural triterpene glycoside capable of rescuing the down-regulation of LATS2 and APC caused by either miR-31-5p or miR-223-3p overexpression, respectively, was used in the in vivo AOM/DSS-induced CAC model. The results showed that pedunculoside (25 mg/kg) substantially mitigated the damage to mice intestine caused by DSS/AOM. These results suggested that miRNAs-elicited post-transcriptional regulation is involved in the pathogenesis of CAC, and CAC can be prevented through targeting key miRNAs that are ectopically expressed in CAC.https://www.frontiersin.org/article/10.3389/fgene.2019.00585/fullcolitis-associated cancerpedunculosidemiR-31-5pmiR-223-3plet-7f-5p |
| spellingShingle | Gang Chen Gang Chen Yuan Feng Xuezheng Li Zhe Jiang Bei Bei Lin Zhang Yueqing Han Yanwu Li Ning Li Ning Li Post-transcriptional Gene Regulation in Colitis Associated Cancer Frontiers in Genetics colitis-associated cancer pedunculoside miR-31-5p miR-223-3p let-7f-5p |
| title | Post-transcriptional Gene Regulation in Colitis Associated Cancer |
| title_full | Post-transcriptional Gene Regulation in Colitis Associated Cancer |
| title_fullStr | Post-transcriptional Gene Regulation in Colitis Associated Cancer |
| title_full_unstemmed | Post-transcriptional Gene Regulation in Colitis Associated Cancer |
| title_short | Post-transcriptional Gene Regulation in Colitis Associated Cancer |
| title_sort | post transcriptional gene regulation in colitis associated cancer |
| topic | colitis-associated cancer pedunculoside miR-31-5p miR-223-3p let-7f-5p |
| url | https://www.frontiersin.org/article/10.3389/fgene.2019.00585/full |
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