| Autor: |
Xijuan Chen, Yingqiang Liu, Qinglan Zhang, Baoxing Liu, Yan Cheng, Yonglei Zhang, Yanan Sun, Junqi Liu |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Molecular Therapy: Nucleic Acids, Vol 24, Iss , Pp 113-126 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2162-2531 |
| DOI: |
10.1016/j.omtn.2020.11.003 |
| Popis: |
Radiotherapeutic resistance is a major obstacle for the effective treatment of colorectal cancer (CRC). MicroRNAs (miRNAs) play a critical role in chemoresistance and radioresistance. Here, we aimed to investigate whether miR-590-3p participates in the radioresistance of CRC. High expression of miR-590-3p and low expression of CLCA4 were found in both CRC tissues and cell lines. CLCA4 was indicated to be a target gene of miR-590-3p. CAF-derived exosomes were extracted and co-cultured with CRC cells, which were then exposed to radiation. CRC cells were transfected with plasmids and injected into nude mice to detect the in vivo effect of CAF-derived exosomes. Treatment with CAF-derived exosomes decreased the sensitivity of CRC cells to radiation. CAF-derived exosomes overexpressing miR-590-3p increased cell survival and the ratio of p-PI3K/PI3K and p-AKT/AKT while lowering the expressions of cleaved-PARP, cleaved-caspase 3, and γH2AX in cells. Furthermore, in vivo experimental results confirmed that CAF-derived exosomal miR-590-3p stimulated tumor growth in mice following radiotherapy. Our results demonstrate that miR-590-3p delivery via exosomes derived from CAFs enhances radioresistance in CRC through the positive regulation of the CLCA4-dependent PI3K/Akt signaling pathway. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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