LncRNA CASC19 Enhances the Radioresistance of Nasopharyngeal Carcinoma by Regulating the miR-340-3p/FKBP5 Axis
Radioresistance remains a serious obstacle encountered in the radiotherapy of nasopharyngeal carcinoma (NPC). Both mRNAs and non-coding RNAs (ncRNAs), including long ncRNA (lncRNA) and microRNA (miRNA), play essential roles in radiosensitivity. However, the comprehensive expression profiles and comp...
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/3/3047 |
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| author | Hongxia Liu Qianping Chen Wang Zheng Yuchuan Zhou Yang Bai Yan Pan Jianghong Zhang Chunlin Shao |
| author_facet | Hongxia Liu Qianping Chen Wang Zheng Yuchuan Zhou Yang Bai Yan Pan Jianghong Zhang Chunlin Shao |
| author_sort | Hongxia Liu |
| collection | DOAJ |
| description | Radioresistance remains a serious obstacle encountered in the radiotherapy of nasopharyngeal carcinoma (NPC). Both mRNAs and non-coding RNAs (ncRNAs), including long ncRNA (lncRNA) and microRNA (miRNA), play essential roles in radiosensitivity. However, the comprehensive expression profiles and competing endogenous RNA (ceRNA) regulatory networks among lncRNAs, miRNAs, and mRNAs in NPC radioresistance are still bewildering. In this study, we performed an RNA-sequencing (RNA-seq) assay in the radioresistant NPC cells CNE2R and its parental cells CNE2 to identify the differentially expressed lncRNAs, miRNAs, and mRNAs. The ceRNA networks containing lncRNAs, miRNAs, and mRNAs were predicted on the basis of the Pearson correlation coefficients and authoritative miRanda databases. In accordance with bioinformatic analysis of the data of the tandem mass tag (TMT) assay of CNE2R and CNE2 cells and the gene chip assay of radioresistant NPC samples in pre- and post-radiotherapy, the radioresistance-related signaling network of lncRNA CASC19, miR-340-3p, and FKBP5 was screened and further verified using an RT-qPCR assay. CASC19 was positively associated with FKBP5 expression while negatively correlated with miR-340-3p, and the target binding sites of CASC19/miR-340-3p and miR-340-3p/FKBP5 were confirmed using a dual-luciferase reporter assay. Moreover, using an mRFP–GFP–LC3 maker, it was found that autophagy contributed to the radioresistance of NPC. MiR-340-3p inhibition or FKBP5 overexpression could rescue the suppression of autophagy and radioresistance induced by CASC19 knockdown in CNE2R cells. In conclusion, the CASC19/miR-340-3p/FKBP5 network may be instrumental in regulating NPC radioresistance by enhancing autophagy, which provides potential new therapeutic targets for NPC. |
| first_indexed | 2024-03-11T09:38:53Z |
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| last_indexed | 2024-03-11T09:38:53Z |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5e8a506e91784e5cb5394beec92778122023-11-16T17:06:18ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01243304710.3390/ijms24033047LncRNA CASC19 Enhances the Radioresistance of Nasopharyngeal Carcinoma by Regulating the miR-340-3p/FKBP5 AxisHongxia Liu0Qianping Chen1Wang Zheng2Yuchuan Zhou3Yang Bai4Yan Pan5Jianghong Zhang6Chunlin Shao7Institute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaInstitute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaInstitute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaInstitute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaInstitute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaInstitute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaInstitute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaInstitute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaRadioresistance remains a serious obstacle encountered in the radiotherapy of nasopharyngeal carcinoma (NPC). Both mRNAs and non-coding RNAs (ncRNAs), including long ncRNA (lncRNA) and microRNA (miRNA), play essential roles in radiosensitivity. However, the comprehensive expression profiles and competing endogenous RNA (ceRNA) regulatory networks among lncRNAs, miRNAs, and mRNAs in NPC radioresistance are still bewildering. In this study, we performed an RNA-sequencing (RNA-seq) assay in the radioresistant NPC cells CNE2R and its parental cells CNE2 to identify the differentially expressed lncRNAs, miRNAs, and mRNAs. The ceRNA networks containing lncRNAs, miRNAs, and mRNAs were predicted on the basis of the Pearson correlation coefficients and authoritative miRanda databases. In accordance with bioinformatic analysis of the data of the tandem mass tag (TMT) assay of CNE2R and CNE2 cells and the gene chip assay of radioresistant NPC samples in pre- and post-radiotherapy, the radioresistance-related signaling network of lncRNA CASC19, miR-340-3p, and FKBP5 was screened and further verified using an RT-qPCR assay. CASC19 was positively associated with FKBP5 expression while negatively correlated with miR-340-3p, and the target binding sites of CASC19/miR-340-3p and miR-340-3p/FKBP5 were confirmed using a dual-luciferase reporter assay. Moreover, using an mRFP–GFP–LC3 maker, it was found that autophagy contributed to the radioresistance of NPC. MiR-340-3p inhibition or FKBP5 overexpression could rescue the suppression of autophagy and radioresistance induced by CASC19 knockdown in CNE2R cells. In conclusion, the CASC19/miR-340-3p/FKBP5 network may be instrumental in regulating NPC radioresistance by enhancing autophagy, which provides potential new therapeutic targets for NPC.https://www.mdpi.com/1422-0067/24/3/3047nasopharyngeal carcinomaradioresistancelncRNA CASC19miR-340-3pFKBP5autophagy |
| spellingShingle | Hongxia Liu Qianping Chen Wang Zheng Yuchuan Zhou Yang Bai Yan Pan Jianghong Zhang Chunlin Shao LncRNA CASC19 Enhances the Radioresistance of Nasopharyngeal Carcinoma by Regulating the miR-340-3p/FKBP5 Axis International Journal of Molecular Sciences nasopharyngeal carcinoma radioresistance lncRNA CASC19 miR-340-3p FKBP5 autophagy |
| title | LncRNA CASC19 Enhances the Radioresistance of Nasopharyngeal Carcinoma by Regulating the miR-340-3p/FKBP5 Axis |
| title_full | LncRNA CASC19 Enhances the Radioresistance of Nasopharyngeal Carcinoma by Regulating the miR-340-3p/FKBP5 Axis |
| title_fullStr | LncRNA CASC19 Enhances the Radioresistance of Nasopharyngeal Carcinoma by Regulating the miR-340-3p/FKBP5 Axis |
| title_full_unstemmed | LncRNA CASC19 Enhances the Radioresistance of Nasopharyngeal Carcinoma by Regulating the miR-340-3p/FKBP5 Axis |
| title_short | LncRNA CASC19 Enhances the Radioresistance of Nasopharyngeal Carcinoma by Regulating the miR-340-3p/FKBP5 Axis |
| title_sort | lncrna casc19 enhances the radioresistance of nasopharyngeal carcinoma by regulating the mir 340 3p fkbp5 axis |
| topic | nasopharyngeal carcinoma radioresistance lncRNA CASC19 miR-340-3p FKBP5 autophagy |
| url | https://www.mdpi.com/1422-0067/24/3/3047 |
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