MiR-378a-5p exerts a radiosensitizing effect on CRC through LRP8/β-catenin axis
ABSTRACTBackground MiRNAs are closely related to tumor radiosensitivity. MiR-378a-5p level is down-regulated in colorectal cancer (CRC). Therefore, this study intends to explore the role of miR-378a-5p in CRC, especially radiosensitivity.Methods The expression of miR-378a-5p was analyzed in CRC samp...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Cancer Biology & Therapy |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/15384047.2024.2308165 |
| _version_ | 1797299719935885312 |
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| author | Guolin Hu Pengbiao Che Ling Deng Lei Liu Jia Liao Qi Liu |
| author_facet | Guolin Hu Pengbiao Che Ling Deng Lei Liu Jia Liao Qi Liu |
| author_sort | Guolin Hu |
| collection | DOAJ |
| description | ABSTRACTBackground MiRNAs are closely related to tumor radiosensitivity. MiR-378a-5p level is down-regulated in colorectal cancer (CRC). Therefore, this study intends to explore the role of miR-378a-5p in CRC, especially radiosensitivity.Methods The expression of miR-378a-5p was analyzed in CRC samples. CRC cell lines were treated with different doses of X-rays. Bioinformatics analysis, dual-luciferase reporter assay and RT-qPCR were used to detect the expressions and binding relationship of miR-378a-5p and low-density lipoprotein receptor-related protein 8 (LRP8). MiR-378a-5p inhibitor or/and siLRP8 were transfected into CRC cells with or without irradiation. Subsequently, clonogenic assay, flow cytometry and in vivo experiments including tumorigenesis assay, immunohistochemistry, RT-qPCR and Western blot were performed to clarify the role of miR-378a-5p/LRP8 axis in the radiosensitivity of CRC.Results The down-regulated expression of miR-378a-5p in CRC is related to histological differentiation and tumor-node-metastasis (TNM) stage. After irradiation, the survival fraction of CRC cells was decreased, while the apoptotic rate and the level of miR-378a-5p were increased. Restrained miR-378a-5p repressed apoptosis and apoptosis-related protein expressions, yet promoted the proliferation and the radioresistance of cells by regulating β-catenin in CRC cells. LRP8 was highly expressed in CRC, and targeted by miR-378a-5p. SiLRP8 improved radiosensitivity and reversed the effect of miR-378a-5p down-regulation on CRC cells. Overexpressed miR-378a-5p and irradiation enhanced the level of miR-378a-5p, yet suppressed the expressions of Ki67 and LRP8 as well as tumorigenesis.Conclusion MiR-378a-5p may exert a radiosensitizing effect on CRC through the LRP8/β-catenin axis, which may be a new therapeutic target for CRC radioresistance. |
| first_indexed | 2024-03-07T22:55:45Z |
| format | Article |
| id | doaj.art-e21f3be6208d4700b105da22cde11d14 |
| institution | Directory Open Access Journal |
| issn | 1538-4047 1555-8576 |
| language | English |
| last_indexed | 2024-03-07T22:55:45Z |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Cancer Biology & Therapy |
| spelling | doaj.art-e21f3be6208d4700b105da22cde11d142024-02-23T04:59:01ZengTaylor & Francis GroupCancer Biology & Therapy1538-40471555-85762024-12-0125110.1080/15384047.2024.2308165MiR-378a-5p exerts a radiosensitizing effect on CRC through LRP8/β-catenin axisGuolin Hu0Pengbiao Che1Ling Deng2Lei Liu3Jia Liao4Qi Liu5Department of Oncology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, ChinaDepartment of Ultrasound, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, ChinaDepartment of Oncology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, ChinaDepartment of Oncology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, ChinaDepartment of Oncology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, ChinaDepartment of Oncology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, ChinaABSTRACTBackground MiRNAs are closely related to tumor radiosensitivity. MiR-378a-5p level is down-regulated in colorectal cancer (CRC). Therefore, this study intends to explore the role of miR-378a-5p in CRC, especially radiosensitivity.Methods The expression of miR-378a-5p was analyzed in CRC samples. CRC cell lines were treated with different doses of X-rays. Bioinformatics analysis, dual-luciferase reporter assay and RT-qPCR were used to detect the expressions and binding relationship of miR-378a-5p and low-density lipoprotein receptor-related protein 8 (LRP8). MiR-378a-5p inhibitor or/and siLRP8 were transfected into CRC cells with or without irradiation. Subsequently, clonogenic assay, flow cytometry and in vivo experiments including tumorigenesis assay, immunohistochemistry, RT-qPCR and Western blot were performed to clarify the role of miR-378a-5p/LRP8 axis in the radiosensitivity of CRC.Results The down-regulated expression of miR-378a-5p in CRC is related to histological differentiation and tumor-node-metastasis (TNM) stage. After irradiation, the survival fraction of CRC cells was decreased, while the apoptotic rate and the level of miR-378a-5p were increased. Restrained miR-378a-5p repressed apoptosis and apoptosis-related protein expressions, yet promoted the proliferation and the radioresistance of cells by regulating β-catenin in CRC cells. LRP8 was highly expressed in CRC, and targeted by miR-378a-5p. SiLRP8 improved radiosensitivity and reversed the effect of miR-378a-5p down-regulation on CRC cells. Overexpressed miR-378a-5p and irradiation enhanced the level of miR-378a-5p, yet suppressed the expressions of Ki67 and LRP8 as well as tumorigenesis.Conclusion MiR-378a-5p may exert a radiosensitizing effect on CRC through the LRP8/β-catenin axis, which may be a new therapeutic target for CRC radioresistance.https://www.tandfonline.com/doi/10.1080/15384047.2024.2308165Colorectal cancermiR-378a-5plow-density lipoprotein receptor-related protein 8β-cateninradiosensitivity |
| spellingShingle | Guolin Hu Pengbiao Che Ling Deng Lei Liu Jia Liao Qi Liu MiR-378a-5p exerts a radiosensitizing effect on CRC through LRP8/β-catenin axis Cancer Biology & Therapy Colorectal cancer miR-378a-5p low-density lipoprotein receptor-related protein 8 β-catenin radiosensitivity |
| title | MiR-378a-5p exerts a radiosensitizing effect on CRC through LRP8/β-catenin axis |
| title_full | MiR-378a-5p exerts a radiosensitizing effect on CRC through LRP8/β-catenin axis |
| title_fullStr | MiR-378a-5p exerts a radiosensitizing effect on CRC through LRP8/β-catenin axis |
| title_full_unstemmed | MiR-378a-5p exerts a radiosensitizing effect on CRC through LRP8/β-catenin axis |
| title_short | MiR-378a-5p exerts a radiosensitizing effect on CRC through LRP8/β-catenin axis |
| title_sort | mir 378a 5p exerts a radiosensitizing effect on crc through lrp8 β catenin axis |
| topic | Colorectal cancer miR-378a-5p low-density lipoprotein receptor-related protein 8 β-catenin radiosensitivity |
| url | https://www.tandfonline.com/doi/10.1080/15384047.2024.2308165 |
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