LncRNA SNHG12 regulates the radiosensitivity of cervical cancer through the miR-148a/CDK1 pathway
Abstract Background Radiation resistance is a major obstacle to the prognosis of cervical cancer (CC) patients. Many studies have confirmed that long non-coding RNAs (lncRNAs) are involved in the regulation of radiosensitivity of cancers. However, whether small nucleolar RNA host gene 12 (SNHG12) re...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-12-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-020-01654-5 |
| _version_ | 1818647177863364608 |
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| author | Chen Wang Shiqing Shao Li Deng Shelian Wang Yongyan Zhang |
| author_facet | Chen Wang Shiqing Shao Li Deng Shelian Wang Yongyan Zhang |
| author_sort | Chen Wang |
| collection | DOAJ |
| description | Abstract Background Radiation resistance is a major obstacle to the prognosis of cervical cancer (CC) patients. Many studies have confirmed that long non-coding RNAs (lncRNAs) are involved in the regulation of radiosensitivity of cancers. However, whether small nucleolar RNA host gene 12 (SNHG12) regulates the radiosensitivity of CC remains unknown. Methods Quantitative real-time polymerase chain reaction was used to measure the expression levels of SNHG12 and microRNA-148a (miR-148a). The radiosensitivity of cells was evaluated by clonogenic assay. Flow cytometry and caspase-3 activity assay were performed to assess the apoptosis ability and cell cycle distribution of cells. Besides, dual-luciferase reporter and RNA immunoprecipitation assay were used to verify the interaction between miR-148a and SNHG12 or cyclin-dependent kinase 1 (CDK1). Also, the protein levels of CDK1, CCND1 and γ-H2AX were detected by western blot analysis. Furthermore, in vivo experiments were conducted to verify the effect of SNHG12 on CC tumor growth. Ki-67 and TUNEL staining were employed to evaluate the proliferation and apoptosis rates in vivo. The hematoxylin and eosin (HE) staining were employed to evaluate the tumor cell morphology. Results SNHG12 was upregulated in CC tissues and cells, and its knockdown improved the radiosensitivity by promoting the radiation-induced apoptosis and cell cycle arrest of CC cells. Also, miR-148a could be sponged by SNHG12 and could target CDK1. MiR-148a inhibitor or CDK1 overexpression could invert the promotion effect of silenced-SNHG12 on CC radiosensitivity. Meanwhile, SNHG12 interference reduced the tumor growth of CC, increased miR-148a expression, and inhibited CDK1 level in vivo. Conclusion LncRNA SNHG12 promoted CDK1 expression to regulate the sensitivity of CC cells to radiation through sponging miR-148a, indicating that SNHG12 could be used as a potential biomarker to treat the radiotherapy resistance of CC patients. |
| first_indexed | 2024-12-17T00:58:24Z |
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| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-17T00:58:24Z |
| publishDate | 2020-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-c2c403dc744448a0ac7a4f2644cca3d92022-12-21T22:09:33ZengBMCCancer Cell International1475-28672020-12-0120111210.1186/s12935-020-01654-5LncRNA SNHG12 regulates the radiosensitivity of cervical cancer through the miR-148a/CDK1 pathwayChen Wang0Shiqing Shao1Li Deng2Shelian Wang3Yongyan Zhang4Department of Obstetrics and Gynecology, Huaihe Hospital of Henan UniversityDepartment of Obstetrics and Gynecology, Huaihe Hospital of Henan UniversityDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Guangxi Medical UniversityDepartment of Obstetrics and Gynecology, Huaihe Hospital of Henan UniversityDepartment of Obstetrics and Gynecology, Huaihe Hospital of Henan UniversityAbstract Background Radiation resistance is a major obstacle to the prognosis of cervical cancer (CC) patients. Many studies have confirmed that long non-coding RNAs (lncRNAs) are involved in the regulation of radiosensitivity of cancers. However, whether small nucleolar RNA host gene 12 (SNHG12) regulates the radiosensitivity of CC remains unknown. Methods Quantitative real-time polymerase chain reaction was used to measure the expression levels of SNHG12 and microRNA-148a (miR-148a). The radiosensitivity of cells was evaluated by clonogenic assay. Flow cytometry and caspase-3 activity assay were performed to assess the apoptosis ability and cell cycle distribution of cells. Besides, dual-luciferase reporter and RNA immunoprecipitation assay were used to verify the interaction between miR-148a and SNHG12 or cyclin-dependent kinase 1 (CDK1). Also, the protein levels of CDK1, CCND1 and γ-H2AX were detected by western blot analysis. Furthermore, in vivo experiments were conducted to verify the effect of SNHG12 on CC tumor growth. Ki-67 and TUNEL staining were employed to evaluate the proliferation and apoptosis rates in vivo. The hematoxylin and eosin (HE) staining were employed to evaluate the tumor cell morphology. Results SNHG12 was upregulated in CC tissues and cells, and its knockdown improved the radiosensitivity by promoting the radiation-induced apoptosis and cell cycle arrest of CC cells. Also, miR-148a could be sponged by SNHG12 and could target CDK1. MiR-148a inhibitor or CDK1 overexpression could invert the promotion effect of silenced-SNHG12 on CC radiosensitivity. Meanwhile, SNHG12 interference reduced the tumor growth of CC, increased miR-148a expression, and inhibited CDK1 level in vivo. Conclusion LncRNA SNHG12 promoted CDK1 expression to regulate the sensitivity of CC cells to radiation through sponging miR-148a, indicating that SNHG12 could be used as a potential biomarker to treat the radiotherapy resistance of CC patients.https://doi.org/10.1186/s12935-020-01654-5Cervical cancerRadiosensitivitySNHG12miR-148aCDK1 |
| spellingShingle | Chen Wang Shiqing Shao Li Deng Shelian Wang Yongyan Zhang LncRNA SNHG12 regulates the radiosensitivity of cervical cancer through the miR-148a/CDK1 pathway Cancer Cell International Cervical cancer Radiosensitivity SNHG12 miR-148a CDK1 |
| title | LncRNA SNHG12 regulates the radiosensitivity of cervical cancer through the miR-148a/CDK1 pathway |
| title_full | LncRNA SNHG12 regulates the radiosensitivity of cervical cancer through the miR-148a/CDK1 pathway |
| title_fullStr | LncRNA SNHG12 regulates the radiosensitivity of cervical cancer through the miR-148a/CDK1 pathway |
| title_full_unstemmed | LncRNA SNHG12 regulates the radiosensitivity of cervical cancer through the miR-148a/CDK1 pathway |
| title_short | LncRNA SNHG12 regulates the radiosensitivity of cervical cancer through the miR-148a/CDK1 pathway |
| title_sort | lncrna snhg12 regulates the radiosensitivity of cervical cancer through the mir 148a cdk1 pathway |
| topic | Cervical cancer Radiosensitivity SNHG12 miR-148a CDK1 |
| url | https://doi.org/10.1186/s12935-020-01654-5 |
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