LINC00323 knockdown suppresses the proliferation, migration, and vascular mimicry of non-small cell lung cancer cells by promoting ubiquitinated degradation of AKAP1

Background: LINC00323, a new long noncoding RNA, is aberrantly expressed in several cancers. However, the expression, function, and mechanism of LINC00323 in non-small cell lung cancer (NSCLC) are unclear. Methods: In the present study, LINC00323, VEGFA, microvessel density (MVD), and AKAP1 levels w...

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Main Authors: Bin Ke, Hai Zhong, Yuxin Gong, Xiaofei Chen, Chenxin Yan, Lin Shi
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-04-01
Series:Non-coding RNA Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S2468054024001707
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author Bin Ke
Hai Zhong
Yuxin Gong
Xiaofei Chen
Chenxin Yan
Lin Shi
author_facet Bin Ke
Hai Zhong
Yuxin Gong
Xiaofei Chen
Chenxin Yan
Lin Shi
author_sort Bin Ke
collection DOAJ
description Background: LINC00323, a new long noncoding RNA, is aberrantly expressed in several cancers. However, the expression, function, and mechanism of LINC00323 in non-small cell lung cancer (NSCLC) are unclear. Methods: In the present study, LINC00323, VEGFA, microvessel density (MVD), and AKAP1 levels were confirmed in NSCLC tissues. Cell proliferation, migration, and vascular mimicry (VM) were examined to assess the effects of LINC00323 and AKAP1 on NSCLC cells. In addition, the interaction between LINC00323 and AKAP1 was verified by RNA pull-down, LC-MS/MS and RNA immunoprecipitation. The ubiquitination level of AKAP1 was also confirmed through coimmunoprecipitation, cycloheximide (CHX) chase, and ubiquitination assays in vitro. Results: Our results revealed that LINC00323 was upregulated in NSCLC tissues and was positively correlated with metastasis, poor prognosis, VEGFA expression, elevated MVD, and AKAP1 expression. Functionally, LINC00323 or AKAP1 knockdown suppressed the proliferation, migration, and VM of NSCLC cells. Mechanistically, LINC00323 could target AKAP1, and LINC00323 knockdown accelerated ubiquitination-mediated AKAP1 protein degradation. Moreover, LINC00323 silencing suppressed NSCLC cell progression by downregulating AKAP1. Conclusions: LINC00323 knockdown prevents NSCLC cell proliferation, migration, and VM formation by targeting AKAP1, indicating that LINC00323 and AKAP1 might be biological targets for NSCLC treatment.
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publishDate 2025-04-01
publisher KeAi Communications Co., Ltd.
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series Non-coding RNA Research
spelling doaj-art-e53c9ae2fcfc43c6bdb9614746ff38c62025-08-20T03:52:19ZengKeAi Communications Co., Ltd.Non-coding RNA Research2468-05402025-04-011113114010.1016/j.ncrna.2024.12.006LINC00323 knockdown suppresses the proliferation, migration, and vascular mimicry of non-small cell lung cancer cells by promoting ubiquitinated degradation of AKAP1Bin Ke0Hai Zhong1Yuxin Gong2Xiaofei Chen3Chenxin Yan4Lin Shi5Department of VIP Ward, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, ChinaDepartment of Thoracic Surgery, Zhujiang Hospital of Southern Medical University, Guangzhou, 510282, Guangdong, ChinaDepartment of Respiratory Diseases, Zhujiang Hospital of Southern Medical University, Guangzhou, 510282, Guangdong, ChinaZhujiang Hospital of Southern Medical University, Guangzhou, 510282, Guangdong, ChinaZhujiang Hospital of Southern Medical University, Guangzhou, 510282, Guangdong, ChinaDepartment of Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, Guangdong, China; Corresponding author: Department of Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou, 510120, Guangdong, China.Background: LINC00323, a new long noncoding RNA, is aberrantly expressed in several cancers. However, the expression, function, and mechanism of LINC00323 in non-small cell lung cancer (NSCLC) are unclear. Methods: In the present study, LINC00323, VEGFA, microvessel density (MVD), and AKAP1 levels were confirmed in NSCLC tissues. Cell proliferation, migration, and vascular mimicry (VM) were examined to assess the effects of LINC00323 and AKAP1 on NSCLC cells. In addition, the interaction between LINC00323 and AKAP1 was verified by RNA pull-down, LC-MS/MS and RNA immunoprecipitation. The ubiquitination level of AKAP1 was also confirmed through coimmunoprecipitation, cycloheximide (CHX) chase, and ubiquitination assays in vitro. Results: Our results revealed that LINC00323 was upregulated in NSCLC tissues and was positively correlated with metastasis, poor prognosis, VEGFA expression, elevated MVD, and AKAP1 expression. Functionally, LINC00323 or AKAP1 knockdown suppressed the proliferation, migration, and VM of NSCLC cells. Mechanistically, LINC00323 could target AKAP1, and LINC00323 knockdown accelerated ubiquitination-mediated AKAP1 protein degradation. Moreover, LINC00323 silencing suppressed NSCLC cell progression by downregulating AKAP1. Conclusions: LINC00323 knockdown prevents NSCLC cell proliferation, migration, and VM formation by targeting AKAP1, indicating that LINC00323 and AKAP1 might be biological targets for NSCLC treatment.http://www.sciencedirect.com/science/article/pii/S2468054024001707Non-small cell lung cancerLINC00323Vascular mimicryAKAP1Ubiquitination
spellingShingle Bin Ke
Hai Zhong
Yuxin Gong
Xiaofei Chen
Chenxin Yan
Lin Shi
LINC00323 knockdown suppresses the proliferation, migration, and vascular mimicry of non-small cell lung cancer cells by promoting ubiquitinated degradation of AKAP1
Non-coding RNA Research
Non-small cell lung cancer
LINC00323
Vascular mimicry
AKAP1
Ubiquitination
title LINC00323 knockdown suppresses the proliferation, migration, and vascular mimicry of non-small cell lung cancer cells by promoting ubiquitinated degradation of AKAP1
title_full LINC00323 knockdown suppresses the proliferation, migration, and vascular mimicry of non-small cell lung cancer cells by promoting ubiquitinated degradation of AKAP1
title_fullStr LINC00323 knockdown suppresses the proliferation, migration, and vascular mimicry of non-small cell lung cancer cells by promoting ubiquitinated degradation of AKAP1
title_full_unstemmed LINC00323 knockdown suppresses the proliferation, migration, and vascular mimicry of non-small cell lung cancer cells by promoting ubiquitinated degradation of AKAP1
title_short LINC00323 knockdown suppresses the proliferation, migration, and vascular mimicry of non-small cell lung cancer cells by promoting ubiquitinated degradation of AKAP1
title_sort linc00323 knockdown suppresses the proliferation migration and vascular mimicry of non small cell lung cancer cells by promoting ubiquitinated degradation of akap1
topic Non-small cell lung cancer
LINC00323
Vascular mimicry
AKAP1
Ubiquitination
url http://www.sciencedirect.com/science/article/pii/S2468054024001707
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