<i>LNX1</i> Contributes to Cell Cycle Progression and Cisplatin Resistance

The ligand of numb-protein X1 (<i>LNX1</i>) acts as a proto-oncogene by inhibiting <i>p53</i> stability; however, the regulation of <i>LNX1</i> expression has not been investigated. In this study, we screened chemicals to identify factors that potentially regulate...

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Main Authors: Minsu Jang, Rackhyun Park, Yea-In Park, Yeonjeong Park, Jin I. Lee, Sim Namkoong, Eun-Ju Lee, Junsoo Park
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/13/16/4066
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spelling doaj-a2ded342538c448c9a6277c8ae2204f52021-08-26T13:35:41ZengMDPI AGCancers2072-66942021-08-01134066406610.3390/cancers13164066<i>LNX1</i> Contributes to Cell Cycle Progression and Cisplatin ResistanceMinsu Jang0Rackhyun Park1Yea-In Park2Yeonjeong Park3Jin I. Lee4Sim Namkoong5Eun-Ju Lee6Junsoo Park7Division of Biological Science and Technology, Yonsei University, Wonju 26493, KoreaDivision of Biological Science and Technology, Yonsei University, Wonju 26493, KoreaDivision of Biological Science and Technology, Yonsei University, Wonju 26493, KoreaDivision of Biological Science and Technology, Yonsei University, Wonju 26493, KoreaDivision of Biological Science and Technology, Yonsei University, Wonju 26493, KoreaDepartment of Biochemistry, Kangwon National University, Chuncheon 24341, KoreaDepartment of Obstetrics and Gynecology, School of Medicine, Chung-Ang University, Seoul 06973, KoreaDivision of Biological Science and Technology, Yonsei University, Wonju 26493, KoreaThe ligand of numb-protein X1 (<i>LNX1</i>) acts as a proto-oncogene by inhibiting <i>p53</i> stability; however, the regulation of <i>LNX1</i> expression has not been investigated. In this study, we screened chemicals to identify factors that potentially regulate <i>LNX1</i> expression. We found that <i>LNX1</i> expression levels were decreased by DNA damage, including that by cisplatin. Upon treatment with lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate (PMA), <i>LNX1</i> expression levels increased. In addition, cell-cycle progression increased upon <i>LNX1</i> expression; the levels of S and G2/M populations were correlated with <i>LNX1</i> expression. Moreover, in CRISPR-Cas9-mediated <i>LNX1</i> knockout cells, we observed a delay in cell-cycle progression and a downregulation of genes encoding the cell-cycle markers cyclin D1 and cyclin E1. Finally, the upregulation of <i>LNX1</i>-activated cell-cycle progression and increased resistance to cisplatin-mediated cell death. Taken together, these results suggest that <i>LNX1</i> contributes to cell-cycle progression and cisplatin resistance.https://www.mdpi.com/2072-6694/13/16/4066<i>LNX1</i>cell cyclecisplatincell death
collection DOAJ
language English
format Article
sources DOAJ
author Minsu Jang
Rackhyun Park
Yea-In Park
Yeonjeong Park
Jin I. Lee
Sim Namkoong
Eun-Ju Lee
Junsoo Park
spellingShingle Minsu Jang
Rackhyun Park
Yea-In Park
Yeonjeong Park
Jin I. Lee
Sim Namkoong
Eun-Ju Lee
Junsoo Park
<i>LNX1</i> Contributes to Cell Cycle Progression and Cisplatin Resistance
Cancers
<i>LNX1</i>
cell cycle
cisplatin
cell death
author_facet Minsu Jang
Rackhyun Park
Yea-In Park
Yeonjeong Park
Jin I. Lee
Sim Namkoong
Eun-Ju Lee
Junsoo Park
author_sort Minsu Jang
title <i>LNX1</i> Contributes to Cell Cycle Progression and Cisplatin Resistance
title_short <i>LNX1</i> Contributes to Cell Cycle Progression and Cisplatin Resistance
title_full <i>LNX1</i> Contributes to Cell Cycle Progression and Cisplatin Resistance
title_fullStr <i>LNX1</i> Contributes to Cell Cycle Progression and Cisplatin Resistance
title_full_unstemmed <i>LNX1</i> Contributes to Cell Cycle Progression and Cisplatin Resistance
title_sort <i>lnx1</i> contributes to cell cycle progression and cisplatin resistance
publisher MDPI AG
series Cancers
issn 2072-6694
publishDate 2021-08-01
description The ligand of numb-protein X1 (<i>LNX1</i>) acts as a proto-oncogene by inhibiting <i>p53</i> stability; however, the regulation of <i>LNX1</i> expression has not been investigated. In this study, we screened chemicals to identify factors that potentially regulate <i>LNX1</i> expression. We found that <i>LNX1</i> expression levels were decreased by DNA damage, including that by cisplatin. Upon treatment with lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate (PMA), <i>LNX1</i> expression levels increased. In addition, cell-cycle progression increased upon <i>LNX1</i> expression; the levels of S and G2/M populations were correlated with <i>LNX1</i> expression. Moreover, in CRISPR-Cas9-mediated <i>LNX1</i> knockout cells, we observed a delay in cell-cycle progression and a downregulation of genes encoding the cell-cycle markers cyclin D1 and cyclin E1. Finally, the upregulation of <i>LNX1</i>-activated cell-cycle progression and increased resistance to cisplatin-mediated cell death. Taken together, these results suggest that <i>LNX1</i> contributes to cell-cycle progression and cisplatin resistance.
topic <i>LNX1</i>
cell cycle
cisplatin
cell death
url https://www.mdpi.com/2072-6694/13/16/4066
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