Lnc-EST885 promotes hepatocellular carcinoma metastasis through PI3K / AKT pathway by interaction with TRAF4

Background: Hepatocellular carcinoma (HCC) represents a major malignancy globally, characterized by high malignancy and intricate molecular mechanisms. This study aims to explore the role of the long non-coding RNA (lncRNA) lnc-EST885 in HCC development. Methods: Cell experiments including FISH, wes...

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Main Authors: Shaoliang Zhu, Gang Wang, Yuxuan Zhang, Mengjie Zou, Zhi Li, Shenhong Qu, Xiaosu Zou, Wenqian Nong, Weiwei Miao, Qicong Chen, Juanmei Mo, Huibing Chen, Lequn Li, Xiaofeng Dong, Honglin Luo
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Translational Oncology
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Online Access:http://www.sciencedirect.com/science/article/pii/S1936523324003802
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author Shaoliang Zhu
Gang Wang
Yuxuan Zhang
Mengjie Zou
Zhi Li
Shenhong Qu
Xiaosu Zou
Wenqian Nong
Weiwei Miao
Qicong Chen
Juanmei Mo
Huibing Chen
Lequn Li
Xiaofeng Dong
Honglin Luo
author_facet Shaoliang Zhu
Gang Wang
Yuxuan Zhang
Mengjie Zou
Zhi Li
Shenhong Qu
Xiaosu Zou
Wenqian Nong
Weiwei Miao
Qicong Chen
Juanmei Mo
Huibing Chen
Lequn Li
Xiaofeng Dong
Honglin Luo
author_sort Shaoliang Zhu
collection DOAJ
description Background: Hepatocellular carcinoma (HCC) represents a major malignancy globally, characterized by high malignancy and intricate molecular mechanisms. This study aims to explore the role of the long non-coding RNA (lncRNA) lnc-EST885 in HCC development. Methods: Cell experiments including FISH, western blot, flow cytometry and functional analysis were used to elucidate the effects of lnc-EST885 on cell proliferation, apoptosis, migration and EMT processes. RNA pull-down and ESI-FT-ICR-MS were used to identify proteins that interact with lnc-EST885 and were verified by RIP-qPCR. Furthermore, the association of lnc-EST885 and TRAF4 with HCC prognosis and metastasis was evaluated through bioinformatics analysis and animal models. Results: lnc-EST885 is one of the lncRNAs with the highest expression levels in M2-type macrophages. The expression of lnc-EST885 in HCC tissues is significantly higher than in normal tissues, and high expression is associated with poor prognosis. Functional experiments have shown that lnc-EST885 significantly promotes the proliferation and migration of liver cancer cells, inhibits apoptosis, and induces EMT. Studies in a mouse lung metastasis model have also confirmed that lnc-EST885 promotes the pulmonary metastasis of HCC cells in vivo. Mechanistic studies have revealed that lnc-EST885 can bind to the TRAF4 protein, activating the PI3K/AKT signaling pathway, thereby promoting the proliferation, migration, and EMT capability of liver cancer cells, contributing to the malignant phenotype of HCC. Conclusion: lnc-EST885 plays a crucial role in the development of liver cancer, serving as a potential biomarker for predicting HCC prognosis and providing a new target for HCC treatment.
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spelling doaj-art-1e4d8e524de345d4acfcd3b9aca010342025-01-22T05:41:29ZengElsevierTranslational Oncology1936-52332025-02-0152102254Lnc-EST885 promotes hepatocellular carcinoma metastasis through PI3K / AKT pathway by interaction with TRAF4Shaoliang Zhu0Gang Wang1Yuxuan Zhang2Mengjie Zou3Zhi Li4Shenhong Qu5Xiaosu Zou6Wenqian Nong7Weiwei Miao8Qicong Chen9Juanmei Mo10Huibing Chen11Lequn Li12Xiaofeng Dong13Honglin Luo14Department of Hepatobiliary, Pancreas and Spleen Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning 530021, ChinaInstitute of Oncology, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning 530021, ChinaDepartment of Nursing, Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine 528400, ChinaDepartment of Nephrology, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning 530021, ChinaDepartment of Nursing, Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine 528400, ChinaInstitute of Oncology, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning 530021, China; Department of Otolaryngology & Head and Neck, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, Nanning, Guangxi 530021, ChinaInstitute of Oncology, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning 530021, ChinaInstitute of Oncology, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning 530021, ChinaInstitute of Oncology, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning 530021, ChinaInstitute of Oncology, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning 530021, ChinaDepartment of Oncology, Guangxi International Zhuang Medicine Hospital, Guangxi University of Chinese Medicine, Nanning, Guangxi 530021, ChinaDepartment of Nursing, Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine 528400, China; Corresponding authors.Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, China; Corresponding authors.Department of Hepatobiliary, Pancreas and Spleen Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning 530021, China; Corresponding authors.Institute of Oncology, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning 530021, China; Corresponding authors.Background: Hepatocellular carcinoma (HCC) represents a major malignancy globally, characterized by high malignancy and intricate molecular mechanisms. This study aims to explore the role of the long non-coding RNA (lncRNA) lnc-EST885 in HCC development. Methods: Cell experiments including FISH, western blot, flow cytometry and functional analysis were used to elucidate the effects of lnc-EST885 on cell proliferation, apoptosis, migration and EMT processes. RNA pull-down and ESI-FT-ICR-MS were used to identify proteins that interact with lnc-EST885 and were verified by RIP-qPCR. Furthermore, the association of lnc-EST885 and TRAF4 with HCC prognosis and metastasis was evaluated through bioinformatics analysis and animal models. Results: lnc-EST885 is one of the lncRNAs with the highest expression levels in M2-type macrophages. The expression of lnc-EST885 in HCC tissues is significantly higher than in normal tissues, and high expression is associated with poor prognosis. Functional experiments have shown that lnc-EST885 significantly promotes the proliferation and migration of liver cancer cells, inhibits apoptosis, and induces EMT. Studies in a mouse lung metastasis model have also confirmed that lnc-EST885 promotes the pulmonary metastasis of HCC cells in vivo. Mechanistic studies have revealed that lnc-EST885 can bind to the TRAF4 protein, activating the PI3K/AKT signaling pathway, thereby promoting the proliferation, migration, and EMT capability of liver cancer cells, contributing to the malignant phenotype of HCC. Conclusion: lnc-EST885 plays a crucial role in the development of liver cancer, serving as a potential biomarker for predicting HCC prognosis and providing a new target for HCC treatment.http://www.sciencedirect.com/science/article/pii/S1936523324003802Long non-coding RNAsHepatocellular carcinomaMetastasisTRAF4Biomarker
spellingShingle Shaoliang Zhu
Gang Wang
Yuxuan Zhang
Mengjie Zou
Zhi Li
Shenhong Qu
Xiaosu Zou
Wenqian Nong
Weiwei Miao
Qicong Chen
Juanmei Mo
Huibing Chen
Lequn Li
Xiaofeng Dong
Honglin Luo
Lnc-EST885 promotes hepatocellular carcinoma metastasis through PI3K / AKT pathway by interaction with TRAF4
Translational Oncology
Long non-coding RNAs
Hepatocellular carcinoma
Metastasis
TRAF4
Biomarker
title Lnc-EST885 promotes hepatocellular carcinoma metastasis through PI3K / AKT pathway by interaction with TRAF4
title_full Lnc-EST885 promotes hepatocellular carcinoma metastasis through PI3K / AKT pathway by interaction with TRAF4
title_fullStr Lnc-EST885 promotes hepatocellular carcinoma metastasis through PI3K / AKT pathway by interaction with TRAF4
title_full_unstemmed Lnc-EST885 promotes hepatocellular carcinoma metastasis through PI3K / AKT pathway by interaction with TRAF4
title_short Lnc-EST885 promotes hepatocellular carcinoma metastasis through PI3K / AKT pathway by interaction with TRAF4
title_sort lnc est885 promotes hepatocellular carcinoma metastasis through pi3k akt pathway by interaction with traf4
topic Long non-coding RNAs
Hepatocellular carcinoma
Metastasis
TRAF4
Biomarker
url http://www.sciencedirect.com/science/article/pii/S1936523324003802
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