Expression of LC3A, LC3B and p62/SQSTM1 autophagy proteins in hepatocellular carcinoma (HCC) tissues and the predicted microRNAs involved in the autophagy-related pathway.

Autor: Wong MM; Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Jalan University, Bandar Sunway, Selangor Darul Ehsan, Subang Jaya, 47500, Malaysia., Aziz NA; Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, National Institutes of Health (NIH Complex), Ministry of Health Malaysia, Level 4, Block C7, No: 1, Jalan Setia Murni U13/52, Section U13, Setia Alam, Selangor Darul Ehsan, Shah Alam, 40170, Malaysia., Ch'ng ES; Advanced Medical and Dental Institute, University Sains Malaysia, 13200 Kepala Batas, Pulau Pinang, Bertam, Malaysia., Armon S; Pathology Department, Hospital Kuala Lumpur, Jalan Pahang, Kuala Lumpur, 50588, Malaysia., Chook JB; Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Jalan University, Bandar Sunway, Selangor Darul Ehsan, Subang Jaya, 47500, Malaysia., Bong JJ; Sunway Medical Centre, 5 Jalan Lagoon Selatan, Bandar Sunway, Subang Jaya, 47500, Selangor, Malaysia., Peh SC; Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Jalan University, Bandar Sunway, Selangor Darul Ehsan, Subang Jaya, 47500, Malaysia.; Sunway Medical Centre, 5 Jalan Lagoon Selatan, Bandar Sunway, Subang Jaya, 47500, Selangor, Malaysia., Wu YS; Sunway Microbiome Centre, School of Medical and Life Sciences, Sunway University, Selangor Darul Ehsan, Subang Jaya, 47500, Malaysia.; Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Selangor Darul Ehsan, Subang Jaya, 47500, Malaysia., Teow SY; Department of Biology, College of Science, Mathematics, and Technology, Wenzhou-Kean University, Daxue Road, Ouhai, Wenzhou, 325060, Zhejiang Province, China. tsinyean@kean.edu.; Wenzhou Municipal Key Laboratory for Applied Biomedical and Biopharmaceutical Informatics, Ouhai, Wenzhou, 325060, Zhejiang Province, China. tsinyean@kean.edu.; Zhejiang Bioinformatics International Science and Technology Cooperation Center, Ouhai, Wenzhou, 325060, Zhejiang Province, China. tsinyean@kean.edu.; Dorothy and George Hennings College of Science, Mathematics and Technology, Kean University, 1000 Morris Ave, Union, NJ, 07083, USA. tsinyean@kean.edu.
Jazyk: angličtina
Zdroj: Journal of molecular histology [J Mol Histol] 2024 Jun; Vol. 55 (3), pp. 317-328. Date of Electronic Publication: 2024 Apr 17.
DOI: 10.1007/s10735-024-10191-8
Abstrakt: Background: Autophagy plays multifaceted roles in regulating hepatocellular carcinoma (HCC) and the mechanisms involved are under-explored. Regulatory microRNAs (miRNAs) have been reported to target autophagy proteins but their roles in HCC is not well studied. Using HCC patient tissues, this study aims to investigate the association of autophagy with several clinicopathological parameters as well as identifying the autophagy-related miRNAs and the possible pathways.
Methods and Results: Autophagy level in the HCC patient-derived cancer and non-cancer tissues was determined by immunohistochemistry (IHC) targeting SQSTM1, LC3A and LC3B proteins. Significance tests of clinicopathological variables were tested using the Fisher's exact or Chi-square tests. Gene and miRNA expression assays were carried out and analyzed using Nanostring platform and software followed by validation of other online bioinformatics tools, namely String and miRabel. Autophagy expression was significantly higher in cancerous tissues compared to adjacent non-cancer tissues. High LC3B expression was associated with advanced tumor histology grade and tumor location. Nanostring gene expression analysis revealed that SQSTM1, PARP1 and ATG9A genes were upregulated in HCC tissues compared to non-cancer tissues while SIRT1 gene was downregulated. These genes are closely related to an autophagy pathway in HCC. Further, using miRabel tool, three downregulated miRNAs (hsa-miR-16b-5p, hsa-miR-34a-5p, and hsa-miR-660-5p) and one upregulated miRNA (hsa-miR-539-5p) were found to closely interact with the abovementioned autophagy-related genes. We then mapped out the possible pathway involving the genes and miRNAs in HCC tissues.
Conclusions: We conclude that autophagy events are more active in HCC tissues compared to the adjacent non-cancer tissues. We also reported the possible role of several miRNAs in regulating autophagy-related genes in the autophagy pathway in HCC. This may contribute to the development of potential therapeutic targets for improving HCC therapy. Future investigations are warranted to validate the target genes reported in this study using a larger sample size and more targeted molecular technique.
(© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)
Databáze: MEDLINE
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