Screening and Validation of a Carvacrol-Targeting Viability-Regulating Protein, SLC6A3, in Liver Hepatocellular Carcinoma.

Publisher: Hindawi Pub. Corp Country of Publication: United States NLM ID: 8604127 Publication Model: eCollection Cited Medium: Internet ISSN: 1875-8630 (Electronic) Linking ISSN: 02780240 NLM ISO Abbreviation: Dis Markers Subsets: MEDLINE

Publication: 2015- : New York, NY : Hindawi Pub. Corp.
Original Publication: Chichester ; New York : Wiley, c1983-

Carcinoma, Hepatocellular*/drug therapy ; Carcinoma, Hepatocellular*/genetics ; Carcinoma, Hepatocellular*/metabolism ; Liver Neoplasms*/drug therapy ; Liver Neoplasms*/genetics ; Liver Neoplasms*/metabolism; Biomarkers, Tumor/genetics ; Cymenes ; Dopamine Plasma Membrane Transport Proteins/genetics ; Dopamine Plasma Membrane Transport Proteins/metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; NAV1.4 Voltage-Gated Sodium Channel/genetics ; NAV1.4 Voltage-Gated Sodium Channel/metabolism

Background: Liver hepatocellular carcinoma (LIHC) is the second leading cause of tumor-related death in the world. Carvacrol was also found to inhibit multiple cancer types. Here, we proposed that Carvacrol inhibited LIHC.
Methods: We used MTT assay to determine the inhibition of Carvacrol on LIHC cells. BATMAN-TCM was used to predict targets of Carvacrol. These targets were further screened by their survival association and expression in cancer using TCGA data. The bioinformatic screened candidates were further validated in in vitro experiments and clinical samples. Finally, docking models of the interaction of Carvacrol and target protein were conducted.
Results: Carvacrol inhibited the viability of LIHC cell lines. 40 target genes of Carvacrol were predicted, 8 of them associated with survival. 4 genes were found differentially expressed in LIHC vs. normal liver. Among these genes, the expression of SLC6A3 and SCN4A was found affected by Carvacrol in LIHC cells, but only SLC6A3 correlated with the viability inhibition of Carvacrol on LIHC cell lines. A docking model of the interaction of Carvacrol and SLC6A3 was established with a good binding affinity. SLC6A3 knockdown and expression revealed that SLC6A3 promoted the viability of LIHC cells.
Conclusion: Carvacrol inhibited the viability of LIHC cells by downregulating SLC6A3.
Competing Interests: The authors declare no conflict of interest.
(Copyright © 2022 Xieling Yin et al.)

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0 (Biomarkers, Tumor)
0 (Cymenes)
0 (Dopamine Plasma Membrane Transport Proteins)
0 (NAV1.4 Voltage-Gated Sodium Channel)
0 (SCN4A protein, human)
0 (SLC6A3 protein, human)
9B1J4V995Q (carvacrol)

Date Created: 20220411 Date Completed: 20220412 Latest Revision: 20240826

20240826

PMC8986433

10.1155/2022/3736104

35401884