LncRNA FGD5-AS1 Facilitates the Radioresistance of Breast Cancer Cells by Enhancing MACC1 Expression Through Competitively Sponging miR-497-5p
BackgroundLncRNA-FGD5-AS1, as an oncogene, participates in the development and progress of various cancers. However, the exact role and the molecular mechanisms by which FGD5-AS1 regulates radiosensitivity in breast cancer (BC) remains largely unknown.MethodsWe used X-Ray weekly-dose-increase method...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-06-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.671853/full |
| _version_ | 1819126778442022912 |
|---|---|
| author | Ji Li Changjiang Lei Bineng Chen Qingfang Zhu |
| author_facet | Ji Li Changjiang Lei Bineng Chen Qingfang Zhu |
| author_sort | Ji Li |
| collection | DOAJ |
| description | BackgroundLncRNA-FGD5-AS1, as an oncogene, participates in the development and progress of various cancers. However, the exact role and the molecular mechanisms by which FGD5-AS1 regulates radiosensitivity in breast cancer (BC) remains largely unknown.MethodsWe used X-Ray weekly-dose-increase method to establish radiation-resistance cell lines. Bioinformatics tools analyze the expression of FGD5-AS1 in breast cancer tissue and evaluated the relationship between FGD5-AS1 and clinic-pathological features. CCK-8 and colony formation were used to analyze cell proliferation. Western blotting and qPCR were applied to detect protein and gene expression, respectively. RNA interference was used to knock down the endogenous gene expression. Luciferase reporter system and immunoprecipitates were applied to verify the target of FGD5-AS1.ResultFGD5-AS1 was overexpressed in BC tissues and radiation-resistance cell lines. Higher levels of FGD5-AS1 predicted poorer clinical characteristics and prognosis. Loss-of-function FGD5-AS1 sensitized BC cells to X-ray, meanwhile, the cell gained radiation-resistance when exogenous FGD5-AS1 was expressed. FGD5-AS1 depletion arrested cells at G0/G1 and triggers cell apoptosis. The starBase database (ENCORI), predicted binding site of miR-497-5p in FGD5-AS1 sequence, and luciferase reporter system and immunoprecipitates verified miR-497-5p was the target of FGD5-AS1. Furthermore, MACC1 was predicted and verified as the target of miR-497-5p. Loss-of-function FGD5-AS1 sensitized ionizing radiation was rescued by the up-regulation of MACC1 and the inhibition of miR-497.ConclusionFGD5-AS1 displays an oncogene profile in CRC; patients with high expression of FGD5-AS1 should benefit less from radiotherapy and need a more frequent follow-up. Besides, FGD5-AS1 may be a potential therapeutic target for CRC. |
| first_indexed | 2024-12-22T08:01:26Z |
| format | Article |
| id | doaj.art-c695ca64cfef4dd0981975a70db80f14 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-22T08:01:26Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-c695ca64cfef4dd0981975a70db80f142022-12-21T18:33:14ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-06-011110.3389/fonc.2021.671853671853LncRNA FGD5-AS1 Facilitates the Radioresistance of Breast Cancer Cells by Enhancing MACC1 Expression Through Competitively Sponging miR-497-5pJi Li0Changjiang Lei1Bineng Chen2Qingfang Zhu3Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, ChinaDepartment of General Surgery, The Fifth Hospital of Wuhan, Wuhan, ChinaDepartment of Rehabilitation Medicine, The 910th Hospital of The People's Liberation Army Joint Logistics Support Unit, Quanzhou, ChinaDepartment of Radiology, China Resources & WISCO General Hospital, Wuhan University of Science and Technology, Wuhan, ChinaBackgroundLncRNA-FGD5-AS1, as an oncogene, participates in the development and progress of various cancers. However, the exact role and the molecular mechanisms by which FGD5-AS1 regulates radiosensitivity in breast cancer (BC) remains largely unknown.MethodsWe used X-Ray weekly-dose-increase method to establish radiation-resistance cell lines. Bioinformatics tools analyze the expression of FGD5-AS1 in breast cancer tissue and evaluated the relationship between FGD5-AS1 and clinic-pathological features. CCK-8 and colony formation were used to analyze cell proliferation. Western blotting and qPCR were applied to detect protein and gene expression, respectively. RNA interference was used to knock down the endogenous gene expression. Luciferase reporter system and immunoprecipitates were applied to verify the target of FGD5-AS1.ResultFGD5-AS1 was overexpressed in BC tissues and radiation-resistance cell lines. Higher levels of FGD5-AS1 predicted poorer clinical characteristics and prognosis. Loss-of-function FGD5-AS1 sensitized BC cells to X-ray, meanwhile, the cell gained radiation-resistance when exogenous FGD5-AS1 was expressed. FGD5-AS1 depletion arrested cells at G0/G1 and triggers cell apoptosis. The starBase database (ENCORI), predicted binding site of miR-497-5p in FGD5-AS1 sequence, and luciferase reporter system and immunoprecipitates verified miR-497-5p was the target of FGD5-AS1. Furthermore, MACC1 was predicted and verified as the target of miR-497-5p. Loss-of-function FGD5-AS1 sensitized ionizing radiation was rescued by the up-regulation of MACC1 and the inhibition of miR-497.ConclusionFGD5-AS1 displays an oncogene profile in CRC; patients with high expression of FGD5-AS1 should benefit less from radiotherapy and need a more frequent follow-up. Besides, FGD5-AS1 may be a potential therapeutic target for CRC.https://www.frontiersin.org/articles/10.3389/fonc.2021.671853/fullbreast cancerradiation sensitivityFGD5-AS1lncRNAMACC1 |
| spellingShingle | Ji Li Changjiang Lei Bineng Chen Qingfang Zhu LncRNA FGD5-AS1 Facilitates the Radioresistance of Breast Cancer Cells by Enhancing MACC1 Expression Through Competitively Sponging miR-497-5p Frontiers in Oncology breast cancer radiation sensitivity FGD5-AS1 lncRNA MACC1 |
| title | LncRNA FGD5-AS1 Facilitates the Radioresistance of Breast Cancer Cells by Enhancing MACC1 Expression Through Competitively Sponging miR-497-5p |
| title_full | LncRNA FGD5-AS1 Facilitates the Radioresistance of Breast Cancer Cells by Enhancing MACC1 Expression Through Competitively Sponging miR-497-5p |
| title_fullStr | LncRNA FGD5-AS1 Facilitates the Radioresistance of Breast Cancer Cells by Enhancing MACC1 Expression Through Competitively Sponging miR-497-5p |
| title_full_unstemmed | LncRNA FGD5-AS1 Facilitates the Radioresistance of Breast Cancer Cells by Enhancing MACC1 Expression Through Competitively Sponging miR-497-5p |
| title_short | LncRNA FGD5-AS1 Facilitates the Radioresistance of Breast Cancer Cells by Enhancing MACC1 Expression Through Competitively Sponging miR-497-5p |
| title_sort | lncrna fgd5 as1 facilitates the radioresistance of breast cancer cells by enhancing macc1 expression through competitively sponging mir 497 5p |
| topic | breast cancer radiation sensitivity FGD5-AS1 lncRNA MACC1 |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.671853/full |
| work_keys_str_mv | AT jili lncrnafgd5as1facilitatestheradioresistanceofbreastcancercellsbyenhancingmacc1expressionthroughcompetitivelyspongingmir4975p AT changjianglei lncrnafgd5as1facilitatestheradioresistanceofbreastcancercellsbyenhancingmacc1expressionthroughcompetitivelyspongingmir4975p AT binengchen lncrnafgd5as1facilitatestheradioresistanceofbreastcancercellsbyenhancingmacc1expressionthroughcompetitivelyspongingmir4975p AT qingfangzhu lncrnafgd5as1facilitatestheradioresistanceofbreastcancercellsbyenhancingmacc1expressionthroughcompetitivelyspongingmir4975p |