Abstract
BackgroundLINC00491 was involved in some tumors development, but its function in liver cancer has not been reported. This study aimed to investigate LINC00491 expression and function in liver cancer progression.MethodsSixty liver cancer cases were enrolled. LINC00491, miR-324-5p and rho-associated kinase 1 (ROCK1) expression in liver cancer patients and cells were detected by quantitative reverse transcription-polymerase chain reaction and Western blot. HUH-7 and SK-Hep-1 cells were transfected to modulate LINC00491, miR-324-5p and ROCK1 expression. Cell counting kit-8 assay, colony formation assay, wound healing assay, Transwell experiment, Tunel assay and flow cytometry were performed to detected HUH-7 and SK-Hep-1 cells proliferation, migration, invasion, apoptosis and cell cycle. Biotin-RNA pull-down assay and Dual-Luciferase Reporter Assay was performed to detect the binding among LINC00491, miR-324-5p and ROCK1. Xenograft tumor and lung metastasis was performed using nude mice. Xenograft tumor and lung tissues of mice were experienced immunohistochemistry and hematoxylin–eosin staining.ResultsLINC00491 was highly expressed in liver cancer cases, associating with poor prognosis. si-LINC00491 inhibited proliferation, colony formation, invasion, migration, and induced cell cycle G1 arrest and apoptosis in HUH-7 and SK-Hep-1 cells. LINC00491 overexpression showed opposite effects. LINC00491 promoted ROCK1 expression by reducing miR-324-5p. miR-324-5p up-regulation or ROCK1 knockdown reversed LINC00491 promotion on liver SK-Hep-1 cells malignant phenotype. LINC00491 facilitated xenograft tumor growth and lung metastasis in mice.ConclusionLINC00491 was highly expressed in liver cancer patients, associating with poor prognosis. LINC00491 facilitated liver cancer progression by sponging miR-324-5p/ROCK1. LINC00491 might be a potential treatment target of liver cancer.
Highlights
Liver cancer is one of the most common malignant tumors
LINC00491 was up‐regulated in liver cancer patients and cells The expression of LINC00491 in 60 pairs of liver cancer tissues and the corresponding adjacent normal tissues was determined by qRT-polymerase chain reaction (PCR)
The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases showed that LINC00491 was highly expressed in tumor tissues than that in normal tissues (P = 0.0029 or 0.013) (Fig. 1B, C)
Summary
Liver cancer is one of the most common malignant tumors. Epidemiological studies have shown that there are significant geographical differences in the incidence of liver cancer; Asia, especially China, has a higherWang et al Journal of Translational Medicine (2021) 19:504 statistics [4]. The early clinical symptoms of liver cancer are not obvious, and are often neglected It is usually diagnosed in middle or advanced stages, where there is a high degree of malignancy, rapid progression, easy recurrence of metastasis after treatment, and poor prognosis [5]. Existing study shows that many lncRNAs and miRNAs play a role in the suppression or promotion of tumor function in several cancers, and can be used as diagnostic markers for predicting the risk of tumorigenesis [9]. Several lncRNAs are closely related to the occurrence and development of liver cancer, such as HOTAIR [13], hepatocellular carcinoma up-regulated EZH2-associated long non-coding RNA (HEIH) [14], down-regulated expression by HBx (Dreh) [15], maternally expressed gene 3 (MEG3) [16] etc. This study aimed to investigate LINC00491 expression and function in liver cancer progression
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