Long Non-Coding RNA GAS5 Promotes BAX Expression by Competing with microRNA-128-3p in Response to 5-Fluorouracil
The acquisition of drug resistance is a major hurdle for effective cancer treatment. Although several efforts have been made to overcome drug resistance, the underlying mechanisms have not been fully elucidated. This study investigated the role of long non-coding RNA (lncRNA) growth arrest-specific...
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MDPI AG
2022-12-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/1/58 |
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| author | Heejin Lee Hoin Kang Chongtae Kim Ja-Lok Ku Sukwoo Nam Eun Kyung Lee |
| author_facet | Heejin Lee Hoin Kang Chongtae Kim Ja-Lok Ku Sukwoo Nam Eun Kyung Lee |
| author_sort | Heejin Lee |
| collection | DOAJ |
| description | The acquisition of drug resistance is a major hurdle for effective cancer treatment. Although several efforts have been made to overcome drug resistance, the underlying mechanisms have not been fully elucidated. This study investigated the role of long non-coding RNA (lncRNA) growth arrest-specific 5 (GAS5) in drug resistance. GAS5 was found to be downregulated in colon cancer cell lines that are resistant to 5-fluorouracil (5-FU). Downregulation of GAS5 decreased the viability of HCT116 cells and the level of the pro-apoptotic BAX protein, while GAS5 overexpression promoted cell death in response to 5-FU. The interaction between GAS5 and <i>BAX</i> mRNA was investigated using MS2-tagged RNA affinity purification (MS2-trap) followed by RT-qPCR, and the results showed that GAS5 bound to the 3′-untranslated region of <i>BAX</i> mRNA and enhanced its expression by interfering with the inhibitory effect of microRNA-128-3p, a negative regulator of BAX. In addition, ectopic expression of GAS5 increased the sensitivity of resistant cells in response to anti-cancer drugs. These results suggest that GAS5 promoted cell death by interfering with miR-128-3p-mediated BAX downregulation. Therefore, GAS5 overexpression in chemo-resistant cancer cells may be a potential strategy to improve the anti-cancer efficacy of drugs. |
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| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T13:30:04Z |
| publishDate | 2022-12-01 |
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| spelling | doaj.art-50c59fac60f143b8aabda1443829cdd02023-11-30T21:18:50ZengMDPI AGBiomedicines2227-90592022-12-011115810.3390/biomedicines11010058Long Non-Coding RNA GAS5 Promotes BAX Expression by Competing with microRNA-128-3p in Response to 5-FluorouracilHeejin Lee0Hoin Kang1Chongtae Kim2Ja-Lok Ku3Sukwoo Nam4Eun Kyung Lee5Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of KoreaDepartment of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of KoreaDepartment of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of KoreaDepartment of Biomedical Sciences, College of Medicine, Seoul National University, Seoul 03080, Republic of KoreaDepartment of Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of KoreaDepartment of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of KoreaThe acquisition of drug resistance is a major hurdle for effective cancer treatment. Although several efforts have been made to overcome drug resistance, the underlying mechanisms have not been fully elucidated. This study investigated the role of long non-coding RNA (lncRNA) growth arrest-specific 5 (GAS5) in drug resistance. GAS5 was found to be downregulated in colon cancer cell lines that are resistant to 5-fluorouracil (5-FU). Downregulation of GAS5 decreased the viability of HCT116 cells and the level of the pro-apoptotic BAX protein, while GAS5 overexpression promoted cell death in response to 5-FU. The interaction between GAS5 and <i>BAX</i> mRNA was investigated using MS2-tagged RNA affinity purification (MS2-trap) followed by RT-qPCR, and the results showed that GAS5 bound to the 3′-untranslated region of <i>BAX</i> mRNA and enhanced its expression by interfering with the inhibitory effect of microRNA-128-3p, a negative regulator of BAX. In addition, ectopic expression of GAS5 increased the sensitivity of resistant cells in response to anti-cancer drugs. These results suggest that GAS5 promoted cell death by interfering with miR-128-3p-mediated BAX downregulation. Therefore, GAS5 overexpression in chemo-resistant cancer cells may be a potential strategy to improve the anti-cancer efficacy of drugs.https://www.mdpi.com/2227-9059/11/1/58long non-coding RNAGAS5competing endogenous RNABAXmicroRNA |
| spellingShingle | Heejin Lee Hoin Kang Chongtae Kim Ja-Lok Ku Sukwoo Nam Eun Kyung Lee Long Non-Coding RNA GAS5 Promotes BAX Expression by Competing with microRNA-128-3p in Response to 5-Fluorouracil Biomedicines long non-coding RNA GAS5 competing endogenous RNA BAX microRNA |
| title | Long Non-Coding RNA GAS5 Promotes BAX Expression by Competing with microRNA-128-3p in Response to 5-Fluorouracil |
| title_full | Long Non-Coding RNA GAS5 Promotes BAX Expression by Competing with microRNA-128-3p in Response to 5-Fluorouracil |
| title_fullStr | Long Non-Coding RNA GAS5 Promotes BAX Expression by Competing with microRNA-128-3p in Response to 5-Fluorouracil |
| title_full_unstemmed | Long Non-Coding RNA GAS5 Promotes BAX Expression by Competing with microRNA-128-3p in Response to 5-Fluorouracil |
| title_short | Long Non-Coding RNA GAS5 Promotes BAX Expression by Competing with microRNA-128-3p in Response to 5-Fluorouracil |
| title_sort | long non coding rna gas5 promotes bax expression by competing with microrna 128 3p in response to 5 fluorouracil |
| topic | long non-coding RNA GAS5 competing endogenous RNA BAX microRNA |
| url | https://www.mdpi.com/2227-9059/11/1/58 |
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