Long Non-Coding RNA GAS5 Promotes BAX Expression by Competing with microRNA-128-3p in Response to 5-Fluorouracil

Heejin Lee; Hoin Kang; Chongtae Kim; Ja Lok Ku; Sukwoo Nam; Eun Kyung Lee

doi:10.3390/biomedicines11010058

Long Non-Coding RNA GAS5 Promotes BAX Expression by Competing with microRNA-128-3p in Response to 5-Fluorouracil

Heejin Lee, Hoin Kang, Chongtae Kim, Ja Lok Ku, Sukwoo Nam, Eun Kyung Lee

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

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 BAX 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 BAX 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.

Original language	English
Article number	58
Journal	Biomedicines
Volume	11
Issue number	1
DOIs	https://doi.org/10.3390/biomedicines11010058
State	Published - Jan 2023

Bibliographical note

Funding Information:
This work was supported by the Basic Science Research Programs through the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (2021R1A2C1004128, 2020R1I1A1A01066968, and 2018R1D1A1B07041324).

Publisher Copyright:
© 2022 by the authors.

Keywords

BAX
competing endogenous RNA
GAS5
long non-coding RNA
microRNA

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/biomedicines11010058

Cite this

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title = "Long Non-Coding RNA GAS5 Promotes BAX Expression by Competing with microRNA-128-3p in Response to 5-Fluorouracil",

abstract = "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 BAX 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 BAX 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.",

keywords = "BAX, competing endogenous RNA, GAS5, long non-coding RNA, microRNA",

author = "Heejin Lee and Hoin Kang and Chongtae Kim and Ku, {Ja Lok} and Sukwoo Nam and Lee, {Eun Kyung}",

note = "Funding Information: This work was supported by the Basic Science Research Programs through the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (2021R1A2C1004128, 2020R1I1A1A01066968, and 2018R1D1A1B07041324). Publisher Copyright: {\textcopyright} 2022 by the authors.",

year = "2023",

month = jan,

doi = "10.3390/biomedicines11010058",

language = "English",

volume = "11",

journal = "Biomedicines",

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AU - Lee, Heejin

AU - Kang, Hoin

AU - Kim, Chongtae

AU - Ku, Ja Lok

AU - Nam, Sukwoo

AU - Lee, Eun Kyung

N1 - Funding Information: This work was supported by the Basic Science Research Programs through the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (2021R1A2C1004128, 2020R1I1A1A01066968, and 2018R1D1A1B07041324). Publisher Copyright: © 2022 by the authors.

PY - 2023/1

Y1 - 2023/1

N2 - 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 BAX 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 BAX 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.

AB - 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 BAX 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 BAX 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.

KW - BAX

KW - competing endogenous RNA

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KW - long non-coding RNA

KW - microRNA

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JO - Biomedicines

JF - Biomedicines

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ER -

Long Non-Coding RNA GAS5 Promotes BAX Expression by Competing with microRNA-128-3p in Response to 5-Fluorouracil

Abstract

Bibliographical note

Keywords

UN SDGs

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Catholic University of Korea Researchers Focus on Cancer (Long Non-Coding RNA GAS5 Promotes BAX Expression by Competing with microRNA-128-3p in Response to 5-Fluorouracil)

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Long Non-Coding RNA GAS5 Promotes BAX Expression by Competing with microRNA-128-3p in Response to 5-Fluorouracil

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Press/Media

Catholic University of Korea Researchers Focus on Cancer (Long Non-Coding RNA GAS5 Promotes BAX Expression by Competing with microRNA-128-3p in Response to 5-Fluorouracil)

Cite this