Long-chain fatty acyl-Coa ligase 4 (ACSL4) is an important enzyme that converts fatty acids to fatty acyl-Coa esters, there is increasing evidence for its role in carcinogenesis. However, the precise role of ACLS4 in hepatocellular carcinoma (HCC) is not clearly understood. In the present study, we provide evidence that ACSL4 expression was specifically elevated in HCC and is associated with poor clinical outcomes. ACSL4 significantly promotes the growth and metastasis of HCC both in vitro and in vivo . RNA sequencing and functional experiments showed that the effect of ACSL4 on HCC development was heavily dependent on PAK2. ACSL4 expression is well correlated with PAK2 in HCC, and ACSL4 even transcriptionally increased PAK2 gene expression mediated by Sp1. In addition, emodin, a naturally occurring anthraquinone derivative, inhibited HCC cell growth and tumor progression by targeting ACSL4. In summary, ACSL4 plays a novel oncogene in HCC development by regulating PAK2 transcription. Targeting ACSL4 could be useful in drug development and therapy for HCC.
Background: Ovarian cancer (OC)is a deadly gynecological malignancy worldwide. It is urgent to identify diagnostic biomarkers of OC to disclose the underlying mechanism.Methods and Materials: Bioinformatics analysis was used to identify target genes. Gene expression was detected and altered by qRT-PCR and cell transfection, respectively. The interaction between RP11-499E18.1 and PAK2, as well as that between PAK2 and SOX2, was determined using RNA pulldown, RNA immunoprecipitation (RIP), and co-immunoprecipitation (co-IP) assay, respectively. Localizations of RP11-499E18.1, PAK2, and SOX2 were respectively determined employing immunohistochemical (IHC), IF, and FISH. The regulatory effects of RP11-499E18.1, PAK2, and SOX2 on OC cell proliferation, migration, colony formation, epithelial–mesenchymal transition (EMT)-related factor expression, and SOX2 nuclear translocation were determined. Finally, the effects of RP11-499E18.1 and PAK2 expression on the tumor growth in nude mice were determined.Results: RP11-499E18.1, PAK2, and SOX2 were selected in our study. RP11-499E18.1 was downregulated, while PAK2 and SOX2 was upregulated in OC tissues and cells. RP11-499E18.1 coexists in the nucleus and cytoplasm of OC cells. There is an interaction between RP11-499E18.1 and PAK2, as well as PAK2 and SOX2 in OC cells. Alteration of RP11-499E18.1 and PAK2 expression both had no influence on PAK2 and SOX2 levels, but PAK2 upregulation notably augmented p-SOX2 level. RP11-499E18.1 overexpression suppressed OC cell proliferation, migration, and colony formation, as well as SOX2 nuclear translocation. Besides, it inhibited tumor growth in nude mice. However, these effects were notably reversed by PAK2 upregulation and eventually offset by SOX2 knockdown. Additionally, RP11-499E18.1 overexpression reduced PAK2–SOX2 interaction and SOX phosphorylation, and increased the binding of RP11-499E18.1 by PAK2.Conclusion: These lines of evidence demonstrated that RP11-499E18.1 might play its tumor suppressor roles in OC via regulation of the RP11-499E18.1–PAK2–SOX2 axis. This research indicated that RP11-499E18.1 might be used as a diagnostic biomarker for OC in the future.
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