Expression, prognosis and preliminary investigation of the mechanism of action of ACTR6, a member of the ARPs gene family, in hepatocellular carcinoma.
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引用次数: 0
Abstract
Background: Hepatocellular carcinoma (HCC) is the third most prevalent cause of cancer-related mortality globally and the sixth most common cancer overall. It is critical to investigate new biomarkers and prognostic variables because there are currently no early diagnostic indicators. Actin-related proteins (ARPs) are involved in transcriptional regulation, chromatin remodeling, and DNA repair-all processes that have been connected to the development of cancer. However, it's still unclear how ARPs and HCC are related.
Methods: Through the examination of databases like The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC), we examined the variations in the expression of ARPs between the transcriptomes of normal tissue and HCC. Furthermore, univariate and multivariate Cox analysis were used to assess the prognostic effects of ARPs. The investigation of immune cell infiltration and possible functional enrichment followed. Additionally, tissue chips containing regional liver cancer specimens were used to confirm ACTR6 expression and the clinical impact of prognosis using an immunohistochemistry (IHC) test. Finally, to investigate the expression and function of ACTR6 in liver cancer cells, real-time qPCR (RT-qPCR) assays, CCK-8, clone creation, cell cycle, and transwell migration and invasion experiments were carried out.
Results: We found that, in addition to ACTR3C, 17 ARPs were significantly overexpressed in HCC compared with normal tissues. In both univariate and multivariate Cox models, ACTR6 and ACTL6A were identified as potential independent risk factors for the prognosis of HCC, with ACTR6 having the lowest p-value. Clinical samples also confirmed this conclusion. Furthermore, ACTR6 overexpression showed a strong connection with immune cell infiltration levels and clinical and pathological factors linked to a poor prognosis. Functionally, knocking down ACTR6 inhibited cell migration and proliferation, produced a G1 cell cycle arrest, and decreased the viability of liver cancer cells.
Conclusion: These findings demonstrate that ACTR6 is highly expressed in HCC and is associated with poor prognosis. In addition, ACTR6 may induce immune cell infiltration and promote hepatocarcinogenesis by regulating the cell cycle.
期刊介绍：
Frontiers in Medicine publishes rigorously peer-reviewed research linking basic research to clinical practice and patient care, as well as translating scientific advances into new therapies and diagnostic tools. Led by an outstanding Editorial Board of international experts, this multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
In addition to papers that provide a link between basic research and clinical practice, a particular emphasis is given to studies that are directly relevant to patient care. In this spirit, the journal publishes the latest research results and medical knowledge that facilitate the translation of scientific advances into new therapies or diagnostic tools. The full listing of the Specialty Sections represented by Frontiers in Medicine is as listed below. As well as the established medical disciplines, Frontiers in Medicine is launching new sections that together will facilitate
- the use of patient-reported outcomes under real world conditions
- the exploitation of big data and the use of novel information and communication tools in the assessment of new medicines
- the scientific bases for guidelines and decisions from regulatory authorities
- access to medicinal products and medical devices worldwide
- addressing the grand health challenges around the world
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