LINC02139 interacts with and stabilizes XIAP to regulate cell proliferation and apoptosis in gastric cancer

Abstract Previous reports showed that long non-coding RNA (lncRNA) participates in the development and progression of tumors. Nevertheless, the effect of LINC02139 and its mechanism on gastric cancer (GC) is still unknown. We revealed that LINC02139 is upregulated in GC cell lines and tissues and hi...

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Main Authors: Miaomiao Pei, Jieming Zhang, Zhen Yu, Ying Peng, Yidong Chen, Siyang Peng, Xiangyang Wei, Jieke Wu, Xiaodong Huang, Yanci Xie, Ping Yang, Linjie Hong, Xiaoting Huang, Xiaosheng Wu, Weimei Tang, Ye Chen, Side Liu, Jianjiao Lin, Li Xiang, Jide Wang
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-024-07202-5
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author Miaomiao Pei
Jieming Zhang
Zhen Yu
Ying Peng
Yidong Chen
Siyang Peng
Xiangyang Wei
Jieke Wu
Xiaodong Huang
Yanci Xie
Ping Yang
Linjie Hong
Xiaoting Huang
Xiaosheng Wu
Weimei Tang
Ye Chen
Side Liu
Jianjiao Lin
Li Xiang
Jide Wang
author_facet Miaomiao Pei
Jieming Zhang
Zhen Yu
Ying Peng
Yidong Chen
Siyang Peng
Xiangyang Wei
Jieke Wu
Xiaodong Huang
Yanci Xie
Ping Yang
Linjie Hong
Xiaoting Huang
Xiaosheng Wu
Weimei Tang
Ye Chen
Side Liu
Jianjiao Lin
Li Xiang
Jide Wang
author_sort Miaomiao Pei
collection DOAJ
description Abstract Previous reports showed that long non-coding RNA (lncRNA) participates in the development and progression of tumors. Nevertheless, the effect of LINC02139 and its mechanism on gastric cancer (GC) is still unknown. We revealed that LINC02139 is upregulated in GC cell lines and tissues and high LINC02139 expression was correlated with the advancement of GC in patients. Functionally, overexpression of LINC02139 promoted, while knockdown of LINC02139 impaired GC cell proliferation, migration, and invasion in vitro and impeded tumorigenesis in a tumor xenograft model in vivo. Mechanistically, LINC02139 directly bound to XIAP and increased the protein level by maintaining its protein stability through inhibition of the ubiquitination and proteasome-dependent degradation pathway. Importantly, the regulatory function of XIAP in LINC02139-mediated oncogenic effects was demonstrated. Both in vitro and in vivo experiments showed that LINC02139 and XIAP collaboratively modulate GC cell growth and apoptosis. Analysis of clinical GC tissues further confirmed the upregulation of XIAP and the positive association between LINC02139 and XIAP expression. These findings established LINC02139 as a driver of tumorigenesis and highlighted the crucial involvement of the LINC02139-XIAP axis in GC progression, suggesting its potential as a promising therapeutic target for combating GC advancement.
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spelling doaj-art-e6a0a0e75a954fcc9d65d28bfb85dc6d2024-11-17T12:42:56ZengNature PortfolioCommunications Biology2399-36422024-11-017111310.1038/s42003-024-07202-5LINC02139 interacts with and stabilizes XIAP to regulate cell proliferation and apoptosis in gastric cancerMiaomiao Pei0Jieming Zhang1Zhen Yu2Ying Peng3Yidong Chen4Siyang Peng5Xiangyang Wei6Jieke Wu7Xiaodong Huang8Yanci Xie9Ping Yang10Linjie Hong11Xiaoting Huang12Xiaosheng Wu13Weimei Tang14Ye Chen15Side Liu16Jianjiao Lin17Li Xiang18Jide Wang19Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityDepartment of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityDepartment of The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People’s Hospital of ShenzhenDepartment of The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People’s Hospital of ShenzhenGuangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical UniversityAbstract Previous reports showed that long non-coding RNA (lncRNA) participates in the development and progression of tumors. Nevertheless, the effect of LINC02139 and its mechanism on gastric cancer (GC) is still unknown. We revealed that LINC02139 is upregulated in GC cell lines and tissues and high LINC02139 expression was correlated with the advancement of GC in patients. Functionally, overexpression of LINC02139 promoted, while knockdown of LINC02139 impaired GC cell proliferation, migration, and invasion in vitro and impeded tumorigenesis in a tumor xenograft model in vivo. Mechanistically, LINC02139 directly bound to XIAP and increased the protein level by maintaining its protein stability through inhibition of the ubiquitination and proteasome-dependent degradation pathway. Importantly, the regulatory function of XIAP in LINC02139-mediated oncogenic effects was demonstrated. Both in vitro and in vivo experiments showed that LINC02139 and XIAP collaboratively modulate GC cell growth and apoptosis. Analysis of clinical GC tissues further confirmed the upregulation of XIAP and the positive association between LINC02139 and XIAP expression. These findings established LINC02139 as a driver of tumorigenesis and highlighted the crucial involvement of the LINC02139-XIAP axis in GC progression, suggesting its potential as a promising therapeutic target for combating GC advancement.https://doi.org/10.1038/s42003-024-07202-5
spellingShingle Miaomiao Pei
Jieming Zhang
Zhen Yu
Ying Peng
Yidong Chen
Siyang Peng
Xiangyang Wei
Jieke Wu
Xiaodong Huang
Yanci Xie
Ping Yang
Linjie Hong
Xiaoting Huang
Xiaosheng Wu
Weimei Tang
Ye Chen
Side Liu
Jianjiao Lin
Li Xiang
Jide Wang
LINC02139 interacts with and stabilizes XIAP to regulate cell proliferation and apoptosis in gastric cancer
Communications Biology
title LINC02139 interacts with and stabilizes XIAP to regulate cell proliferation and apoptosis in gastric cancer
title_full LINC02139 interacts with and stabilizes XIAP to regulate cell proliferation and apoptosis in gastric cancer
title_fullStr LINC02139 interacts with and stabilizes XIAP to regulate cell proliferation and apoptosis in gastric cancer
title_full_unstemmed LINC02139 interacts with and stabilizes XIAP to regulate cell proliferation and apoptosis in gastric cancer
title_short LINC02139 interacts with and stabilizes XIAP to regulate cell proliferation and apoptosis in gastric cancer
title_sort linc02139 interacts with and stabilizes xiap to regulate cell proliferation and apoptosis in gastric cancer
url https://doi.org/10.1038/s42003-024-07202-5
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