LncRNA THUMPD3-AS1/microRNA-4465/KPNA2 axis impacts human hepatocellular carcinoma cell phenotypes

IF 3.5 3区环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Regenerative Therapy Pub Date : 2025-03-01 Epub Date: 2025-01-23 DOI:10.1016/j.reth.2025.01.010

Jiawei Wang , Chunzhong Qiao , Baoyang Luo , Lei Qin

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Abstract

Objective

Hepatocellular carcinoma (HCC) is a lethal malignancy in the world. LncRNA THUMPD3-AS1 is implicated in tumorigenesis and progression in various tumors. Therefore, this study was applied to investigate the action of THUMPD3-AS1 in HCC by regulating microRNA (miR)-4465 and KPNA2.

Methods

The clinical specimens of HCC were collected to determine THUMPD3-AS1, KPNA2, miR-4465, E-cadherin, Vimentin, N-cadherin, ZEB1 and SNAIL levels. HCC cells were screened and transfected with sh-THUMPD3-AS1 or miR-4465 mimic to explore their roles in HCC cell phenotype and epithelial-mesenchymal transition (EMT)-related factors. The involvement of miR-4465 in THUMPD3-AS1-mediated HCC was proved. The relationship of THUMPD3-AS1, KPNA2 and miR-4465 was verified.

Results

Overexpressed THUMPD3-AS1 and KPNA2 and reduced miR-4465 were present in HCC clinical tissues. THUMPD3-AS1 bound to miR-4465 to target KPNA2. Silencing of THUMPD3-AS1 or restoration of miR-4465 repressed HCC cell phenotypes and EMT in vitro. Inhibition of miR-4465 mitigated the role of silenced THUMPD3-AS1 in HCC.

Conclusion

This study stresses that THUMPD3-AS1 induces EMT in HCC cells and ultimately promotes HCC cell growth and migration by competitively inhibiting miR-4465 expression and thus upregulating KPNA2.

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LncRNA THUMPD3-AS1/microRNA-4465/KPNA2轴影响人肝癌细胞表型

目的肝细胞癌（HCC）是世界范围内的一种致死性恶性肿瘤。LncRNA THUMPD3-AS1参与多种肿瘤的发生和进展。因此，本研究旨在探讨THUMPD3-AS1通过调控microRNA (miR)-4465和KPNA2在HCC中的作用。方法收集HCC临床标本，检测THUMPD3-AS1、KPNA2、miR-4465、E-cadherin、Vimentin、N-cadherin、ZEB1、SNAIL水平。筛选HCC细胞并用sh-THUMPD3-AS1或miR-4465 mimic转染，探讨其在HCC细胞表型和上皮-间质转化（EMT）相关因素中的作用。证实了miR-4465参与thumpd3 - as1介导的HCC。验证THUMPD3-AS1、KPNA2与miR-4465的关系。结果HCC临床组织中存在THUMPD3-AS1、KPNA2过表达，miR-4465过表达。THUMPD3-AS1结合miR-4465靶向KPNA2。在体外，沉默THUMPD3-AS1或恢复miR-4465可抑制HCC细胞表型和EMT。抑制miR-4465可减轻沉默的THUMPD3-AS1在HCC中的作用。本研究强调THUMPD3-AS1在HCC细胞中诱导EMT，最终通过竞争性抑制miR-4465表达，从而上调KPNA2，促进HCC细胞生长和迁移。

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来源期刊

Regenerative Therapy Engineering-Biomedical Engineering

CiteScore

6.00

自引率

2.30%

发文量

106

审稿时长

49 days

期刊介绍： Regenerative Therapy is the official peer-reviewed online journal of the Japanese Society for Regenerative Medicine. Regenerative Therapy is a multidisciplinary journal that publishes original articles and reviews of basic research, clinical translation, industrial development, and regulatory issues focusing on stem cell biology, tissue engineering, and regenerative medicine.