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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Summary: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.
ISSN:1936-5233