Purpose To clarify the underlying regulatory mechanisms of progression from liver cirrhosis to hepatocellular carcinoma (HCC), we analyzed the microbiomics, metabolomics, and proteomics in plasma and tissues from patients with HCC or decompensated liver cirrhosis (DC). Patients and Methods Tissues and plasma from 44 HCC patients and 28 patients with DC were collected for metabolomic analysis. 16S rRNA sequencing was performed in nine HCC tissues (HCCT), four distal noncancerous tissues (HCCN), and 11 DC tissues (DCT). Five HCC tissues had liver cirrhosis (HCCT-LC). Five hepatocellular carcinoma tissues without liver cirrhosis (HCCT-NLC) and five DCT were selected for proteomic sequencing. After combining proteomic and metabolomic analysis, we constructed a mouse model of chronic liver injury using carbon tetrachloride (CCl4) and treated them with vitamin B6 (VB6). Results 16s rRNA sequence results showed that HCC tissues had higher alpha diversity. The highest LDA scores were detected for Elizabethkingia in HCCT, Subsaxibacter in DCT, and Stenotrophomon in HCCN. Metabolomics results demonstrated some metabolites, including capric acid, L-threonate, choline, alpha-D-Glucose, D-ribose, betaine, 2E-eicosenoic acid, linoleic acid, L-palmitoylcarnitine, taurodeoxycholic acid, L-pyroglutamic acid, androsterone sulfate, and phthalic acid mono-2-ethylhexyl ester (MEHP), had better diagnostic efficacy than AFP (AUC: 0.852; 95% CI: 0.749, 0.954). In a combined analysis of metabolomics and proteomics, we found that HCCT-LC had more obvious disorders of VB6 metabolism and pentose and glucuronate interconversions than DCT, and kynurenine metabolism disorder was more significant in HCCT-LC than in HCCT-NLC. In the CCl4-induced chronic liver injury model, after VB6 supplementation, inflammatory cell infiltration, hepatocyte edema, and degeneration were significantly improved. Conclusion We found significant differences in the flora distribution between HCCT and DC; MEHP was a new diagnostic biomarker of HCC, and VB6 ameliorated the inflammatory cell infiltration, hepatocyte edema, and degeneration in chronic liver injury.
PurposeHepatocellular carcinoma (HCC), a worldwide leading cause of morbidity and mortality, is the most frequent primary liver tumor. Most HCC patients are diagnosed with advanced liver cancer, resulting in a very low 5-year survival rate. Thus, there is an urgent need for the development of targeted therapies. In this study, we aimed to investigate the effect and mechanism of the miR-20a/EZH1 axis on the proliferation and metastasis of HCC and the inhibitory effect of the EZH1/EZH2 inhibitor UNC1999 on HCC.Materials and MethodsThe expression of miR-20a in human HCC tissues and cell lines was detected using quantitative real-time PCR (qRT-PCR). The expressions of proteins were analyzed with immunohistochemistry and Western blotting. Luciferase assay was used to verify whether miR-20a targets EZH1 or EZH2. The effect of miR-20a on HCC progression was studied in vivo and in vitro. The tumor inhibitory effect of UNC1999 was confirmed in vivo. CCK8 assay, wound healing assay, cell migration and invasion assay were used to evaluate the synergistic effect of UNC1999 with sorafenib. RNA sequencing (RNA-seq) was performed to screen the differentially expressed genes in the Huh7 and SMMC7721 cell lines after UNC1999, sorafenib, and combination treatments.ResultsIn this study, miR-20a showed a lower expression in both HCC tissues and cell lines. MiR-20a inhibited the proliferation and migration of SMMC7721 and Huh7 cells. The results of the luciferase assay and Western blot analysis revealed that miR-20a directly targeted EZH1, a histone methyltransferase. We demonstrated that miR-20a negatively regulated the expression of EZH1 and inhibited the proliferation and metastasis of HCC by reducing H3K27 methylation. We found UNC1999 inhibited tumor cells proliferation and enhanced the inhibitory effect of sorafenib.ConclusionWe demonstrated that miR-20a suppresses the tumor proliferation and metastasis in HCC by directly targeting EZH1. UNC1999 can inhibit tumor proliferation in vivo and increase the sensitivity of hepatoma cell lines to sorafenib.
Symbol-pair codes introduced by Cassuto and Blaum in 2010 are designed to protect against the pair errors in symbol-pair read channels. One of the central themes in symbol-error correction is the construction of maximal distance separable (MDS) symbol-pair codes that possess the largest possible pair-error correcting performance. In this paper, we construct more general generator polynomials for two classes of MDS symbol-pair codes with code length l p. Based on repeatedroot cyclic codes, we derive all MDS symbol-pair codes of length 3p, when the degree of the generator polynomials is no more than 10. We also give two new classes of (almost maximal distance separable) AMDS symbol-pair codes with the length l p or 4p by virtue of repeatedroot cyclic codes. For length 3p, we derive all AMDS symbol-pair codes, when the degree of the generator polynomials is less than 10. The main results are obtained by determining the solutions of certain equations over finite fields.
Symbol-pair codes introduced by Cassuto and Blaum in 2010 are designed to protect against the pair errors in symbol-pair read channels. One of the central themes in symbol-error correction is the construction of maximal distance separable (MDS) symbol-pair codes that possess the largest possible pair-error correcting performance. Based on repeated-root cyclic codes, we construct two classes of MDS symbol-pair codes for more general generator polynomials and also give a new class of almost MDS (AMDS) symbol-pair codes with the length l p. In addition, we derive all MDS and AMDS symbol-pair codes with length 3p, when the degree of the generator polynomials is no more than 10. The main results are obtained by determining the solutions of certain equations over finite fields.
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