Abstract
BackgroundHyperoside (Hy) is a plant-derived quercetin 3-d-galactoside that exhibits inhibitory activities on various tumor types. The objective of the current study was to explore Hy effects on cervical cancer cell proliferation, and to perform a transcriptome analysis of differentially expressed genes.MethodsCervical cancer HeLa and C-33A cells were cultured and the effect of Hy treatment was determined using the Cell Counting Kit-8 (CCK-8) assay. After calculating the IC50 of Hy in HeLa and C-33A cells, the more sensitive to Hy treatment cell type was selected for RNA-Seq. Differentially expressed genes (DEGs) were identified by comparing gene expression between the Hy and control groups. Candidate genes were determined through DEG analysis, protein interaction network (PPI) construction, PPI module analysis, transcription factor (TF) prediction, TF-target network construction, and survival analysis. Finally, the key candidate genes were verified by RT-qPCR and western blot.ResultsHy inhibited HeLa and C33A cell proliferation in a dose- and time-dependent manner, as determined by the CCK-8 assay. Treatment of C-33A cells with 2 mM Hy was selected for the subsequent experiments. Compared with the control group, 754 upregulated and 509 downregulated genes were identified after RNA-Seq. After functional enrichment, 74 gene ontology biological processes and 43 Kyoto Encyclopedia of Genes and Genomes pathways were obtained. According to the protein interaction network (PPI), PPI module analysis, TF-target network construction, and survival analysis, the key genes MYC, CNKN1A, PAX2, TFRC, ACOX2, UNC5B, APBA1, PRKACA, PEAR1, COL12A1, CACNA1G, PEAR1, and CCNA2 were detected. RT-qPCR was performed on the key genes, and Western blot was used to verify C-MYC and TFRC. C-MYC and TFRC expressions were lower and higher than the corresponding values in the control group, respectively, in accordance with the results from the RNA-Seq analysis.ConclusionHy inhibited HeLa and C-33A cell proliferation through C-MYC gene expression reduction in C-33A cells and TFRC regulation. The results of the current study provide a theoretical basis for Hy treatment of cervical cancer.
Highlights
Hyperoside (Hy) is a plant-derived quercetin 3-d-galactoside that exhibits inhibitory activities on various tumor types
Human papillomavirus (Hpv) vaccination has emerged as an effective method for cervical cancer prevention [1]
Hy effect on HeLa and C‐33A cell proliferation After 24 h in culture, the proliferation rate of HeLa cells decreased by 6.60%, 11.37%, 14.68%, 20.65%, 28.24%, and 50.16% (P < 0.01) in the presence of 0.25, 0.5, 1, 2, 4, and 8 mM Hy, respectively, compared to that of the control group (Fig. 1a)
Summary
Hyperoside (Hy) is a plant-derived quercetin 3-d-galactoside that exhibits inhibitory activities on various tumor types. The objective of the current study was to explore Hy effects on cervical cancer cell proliferation, and to perform a transcriptome analysis of differentially expressed genes. Several reports have implicated traditional Chinese medicines in the treatment of cervical cancer. Ferulic acid inhibits the proliferation, invasion, and autophagy of cervical cancer cells, and induces cell cycle arrest [5]. Casticin induces G0/G1 cell cycle arrest and apoptosis in gallbladder cancer [6]. Hyperoside (Hy) is a flavonoid found mainly in Chinese herbal medicines It exhibits anti-inflammatory, anti-oxidative, and vascular protective effects. Another study implicated Hy in the caspase-3, p53, and nuclear factor-kappa B (NF-κB) signaling pathways, which induce apoptosis and inhibit lung cancer cell proliferation [9, 10]. Hy effect on cervical cancer development and the molecular mechanism implicated are unclear
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