ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2024; 15(12):3809-3824. doi:10.7150/jca.91756 This issue Cite
Research Paper
LINC01535 promotes hepatocellular carcinoma proliferation and metastasis by regulating the miR-214-3p/VASP axis
1. Department of General Surgery, Shaoxing People's Hospital, Shaoxing, 312000, China.
2. Department of Hepatobiliary Surgery, Kunshan Hospital of Traditional Chinese Medicine, Suzhou, 215000, China.
3. Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, China.
4. Department of Hepatopancreatobiliary Surgery, Jiangnan University Medical Center, Wuxi, 214002, China.
*These authors contributed equally to this work.
Abstract
Background: Emerging evidence has indicated that long noncoding RNAs (lncRNAs) are associated with the development and progression of several carcinomas, including hepatocellular carcinoma (HCC). However, the role of LINC01535 in HCC is still unknown.
Materials and methods: In this study, RNA-seq, CCK-8, colony formation, wound healing, Transwell and tumor xenograft assays were used to explore the function of LINC01535 in the proliferation and metastasis of HCC in vitro and in vivo. Fluorescence in situ hybridization (FISH) assay, bioinformatics analysis, dual-luciferase assay, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot analysis were used to reveal the interactions of LINC01535, miR-214-3p and VASP.
Results: LINC01535 was overexpressed in HCC tissues and HCC cell lines. Gain- and loss-of-function studies revealed that LINC01535 could promote HCC cell proliferation, migration and invasion both in vitro and in vivo. In addition, upregulation of LINC01535 significantly decreased the expression of microRNA-214-3p (miR-214-3p), which was found closely associated with suppressing tumor progression. Moreover, VASP was identified as a direct downstream target gene of miR-214-3p. LINC01535 positively regulated VASP expression by sponging miR-214-3p, and VASP overexpression activated the PI3K/AKT signaling pathway and stimulated epithelial-to-mesenchymal transition (EMT) in HCC.
Conclusions: Our study first found that LINC01535 promoted HCC progression by regulating its downstream target, the miR-214-3p/VASP axis, via the PI3K/AKT signaling pathway. The function and novel regulatory mechanism of LINC01535 may provide a valuable target for the diagnosis and treatment of HCC patients.
Keywords: LINC01535, miR-214-3p, VASP, HCC, proliferation, metastasis
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