Novel Long Noncoding RNA 005620 Induces Epirubicin Resistance in Triple-Negative Breast Cancer by Regulating ITGB1 Expression
Triple-negative breast cancer (TNBC) is often treated with anthracyclines (e.g., epirubicin or doxorubicin), but very little is known about anthracycline resistance, especially epirubicin resistance in TNBC. To identify novel long noncoding RNAs (lncRNAs) involved in epirubicin resistance in TNBC, w...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.592215/full |
| _version_ | 1830192932921016320 |
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| author | Fengliang Wang Fengliang Wang Sujin Yang Mingming Lv Fei Chen Hong Yin Sheng Gao Jinhai Tang Jing Yu |
| author_facet | Fengliang Wang Fengliang Wang Sujin Yang Mingming Lv Fei Chen Hong Yin Sheng Gao Jinhai Tang Jing Yu |
| author_sort | Fengliang Wang |
| collection | DOAJ |
| description | Triple-negative breast cancer (TNBC) is often treated with anthracyclines (e.g., epirubicin or doxorubicin), but very little is known about anthracycline resistance, especially epirubicin resistance in TNBC. To identify novel long noncoding RNAs (lncRNAs) involved in epirubicin resistance in TNBC, we established a new TNBC MDA-MB-231 cell line that was resistant to epirubicin (Epi-R). A total of 12 differentially expressed lncRNAs were identified using RNA sequencing analysis of Epi-R cells. Among these lncRNAs, we found a novel intronic lncRNA, lnc005620, was highly expressed in Epi-R cells and human TNBC tissues. Further gain- and loss-of-function studies demonstrated that lnc005620 played an oncogenic role and partially abrogated the effects of epirubicin on TNBC cells. Using iTRAQ proteomics analysis, we found that three members of the integrin family, integrin β4, integrin β1 and integrin α6, were all upregulated in Epi-R MDA-MB-231 cells. Integrin β1, encoded by the ITGB1 gene, was validated to be a downstream target of lnc005620 in Epi-R MDA-MB-231 cells. Our study demonstrates that novel lnc005620 promotes TNBC progression and chemoresistance to epirubicin via integrin β1 both in vitro and in vivo and provides a promising therapeutic target for TNBC patients in terms of enhancing the benefits of epirubicin treatment. |
| first_indexed | 2024-12-18T00:04:23Z |
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| id | doaj.art-5c9ae030adbe4a81bc7f5ae15e5fb5be |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-18T00:04:23Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-5c9ae030adbe4a81bc7f5ae15e5fb5be2022-12-21T21:27:50ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-03-011110.3389/fonc.2021.592215592215Novel Long Noncoding RNA 005620 Induces Epirubicin Resistance in Triple-Negative Breast Cancer by Regulating ITGB1 ExpressionFengliang Wang0Fengliang Wang1Sujin Yang2Mingming Lv3Fei Chen4Hong Yin5Sheng Gao6Jinhai Tang7Jing Yu8Department of Breast Surgery, The Affiliated Obstetrics and Gynaecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, ChinaDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Breast Surgery, The Affiliated Obstetrics and Gynaecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, ChinaDepartment of Breast Surgery, The Affiliated Obstetrics and Gynaecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, ChinaDepartment of Breast Surgery, The Affiliated Obstetrics and Gynaecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, ChinaDepartment of Breast Surgery, The Affiliated Obstetrics and Gynaecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, ChinaDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDivision of Geriatric Endocrinology, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaTriple-negative breast cancer (TNBC) is often treated with anthracyclines (e.g., epirubicin or doxorubicin), but very little is known about anthracycline resistance, especially epirubicin resistance in TNBC. To identify novel long noncoding RNAs (lncRNAs) involved in epirubicin resistance in TNBC, we established a new TNBC MDA-MB-231 cell line that was resistant to epirubicin (Epi-R). A total of 12 differentially expressed lncRNAs were identified using RNA sequencing analysis of Epi-R cells. Among these lncRNAs, we found a novel intronic lncRNA, lnc005620, was highly expressed in Epi-R cells and human TNBC tissues. Further gain- and loss-of-function studies demonstrated that lnc005620 played an oncogenic role and partially abrogated the effects of epirubicin on TNBC cells. Using iTRAQ proteomics analysis, we found that three members of the integrin family, integrin β4, integrin β1 and integrin α6, were all upregulated in Epi-R MDA-MB-231 cells. Integrin β1, encoded by the ITGB1 gene, was validated to be a downstream target of lnc005620 in Epi-R MDA-MB-231 cells. Our study demonstrates that novel lnc005620 promotes TNBC progression and chemoresistance to epirubicin via integrin β1 both in vitro and in vivo and provides a promising therapeutic target for TNBC patients in terms of enhancing the benefits of epirubicin treatment.https://www.frontiersin.org/articles/10.3389/fonc.2021.592215/fulltriple-negative breast cancerepirubicin resistancelong noncoding RNAITGB1MDA-MB-231 |
| spellingShingle | Fengliang Wang Fengliang Wang Sujin Yang Mingming Lv Fei Chen Hong Yin Sheng Gao Jinhai Tang Jing Yu Novel Long Noncoding RNA 005620 Induces Epirubicin Resistance in Triple-Negative Breast Cancer by Regulating ITGB1 Expression Frontiers in Oncology triple-negative breast cancer epirubicin resistance long noncoding RNA ITGB1 MDA-MB-231 |
| title | Novel Long Noncoding RNA 005620 Induces Epirubicin Resistance in Triple-Negative Breast Cancer by Regulating ITGB1 Expression |
| title_full | Novel Long Noncoding RNA 005620 Induces Epirubicin Resistance in Triple-Negative Breast Cancer by Regulating ITGB1 Expression |
| title_fullStr | Novel Long Noncoding RNA 005620 Induces Epirubicin Resistance in Triple-Negative Breast Cancer by Regulating ITGB1 Expression |
| title_full_unstemmed | Novel Long Noncoding RNA 005620 Induces Epirubicin Resistance in Triple-Negative Breast Cancer by Regulating ITGB1 Expression |
| title_short | Novel Long Noncoding RNA 005620 Induces Epirubicin Resistance in Triple-Negative Breast Cancer by Regulating ITGB1 Expression |
| title_sort | novel long noncoding rna 005620 induces epirubicin resistance in triple negative breast cancer by regulating itgb1 expression |
| topic | triple-negative breast cancer epirubicin resistance long noncoding RNA ITGB1 MDA-MB-231 |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.592215/full |
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