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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Han, Hu Li, Yan Qin, Wan Wang, Lu Yin, Han Su, Beibei Yuan, Xianglin |
| Abstract | Background Despite advances in the development of efficient chemotherapy, the treatment of colorectal cancer (CRC) remains a challenge due to acquired chemoresistance. It has been reported that microRNAs (miRNAs) dysregulation is associated with the development of chemoresistance. Recently, the expression of miR-199b-3p has been found to be significantly different between cetuximab (CTx)-resistant and -sensitive CRC cells. However, its role and the underlying mechanisms in acquired chemoresistance to CTx in CRC are still obscure. Methods Here we report that miR-199b-3p is significantly up-regulated in both CTx-resistant (CTxR) CRC tissues and cell lines. Results Functional assays showed that suppressing miR-199b-3p could improve the sensitivity of CRC-CTxR cells to CTx, thereby reducing cell proliferation, migration and invasion, and enhancing cell apoptosis. Mechanistic studies revealed that CRIM1 is a direct target of miR-199b-3p in CRC-CTxR cells; and the effect of miR-199b-3p on CTx-resistance was exerted by regulating the Wnt/β-catenin signaling pathway via CRIM1. Furthermore, mice xenograft models were established and confirmed that down-regulating miR-199b-3p restores the inhibition effect of CTx on tumor growth in CRC-CTxR. Collectively, our data suggest that silencing miR-199b-3p could enhance the anti-tumor effects of CTx on CTx-resistant CRC in vitro and in vivo by activating Wnt/β-catenin signaling via the down-regulation of CRIM1. Conclusions Our findings suggest miR-199b-3p might serve as a promising therapeutic target against CTx resistant CRC, and provide scientific information for exploring novel strategies of improving the efficacy of CTx for CRC patients. |
| Related Links | https://cancerci.biomedcentral.com/counter/pdf/10.1186/s12935-022-02460-x.pdf |
| Ending Page | 16 |
| Page Count | 16 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 14752867 |
| DOI | 10.1186/s12935-022-02460-x |
| Journal | Cancer Cell International |
| Issue Number | 1 |
| Volume Number | 22 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2022-01-28 |
| Access Restriction | Open |
| Subject Keyword | Cancer Research Cell Biology Colorectal cancer Cetuximab microRNA Chemoresistance Wnt/β-catenin signaling Therapeutic target |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Genetics Oncology |
| Journal Impact Factor | 5.3/2023 |
| 5-Year Journal Impact Factor | 5/2023 |
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