Browsing by Author "Liu, Huidi"

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    Enterolactone has stronger effects than enterodiol on ovarian cancer
    (2017-07-24) Liu, Huidi; Liu, Jianrui; Wang, Siwen; Zeng, Zheng; Li, Ting; Liu, Yongfang; Mastriani, Emilio; Li, Qing-Hai; Bao, Hong-Xia; Zhou, Yu-Jie; Wang, Xiaoyu; Hu, Sijing; Gao, Shan; Qi, Yingying; Shen, Zhihang; Wang, Hongyue; Yu, Miao; Gao, Tingting; Johnston, Randal N; Liu, Shu-Lin
    Abstract Background Ovarian cancer is one of the three leading gynecological malignancies, characterized by insidious growth, highly frequent metastasis, and quick development of drug resistance. As a result, this disease has low 5-year survival rates. Estrogen receptor inhibitors were commonly used for the treatment, but only 7% to 18% of patients respond to anti-estrogen therapies. Therefore, more effective therapies to inhibit estrogen-related tumors are urgently needed. Recently, phytoestrogens, such as lignans with estrogen-like biological activities, have attracted attention for their potential effects in the prevention or treatment of estrogen-related diseases. Enterodiol (END) and enterolactone (ENL) are mammalian lignans, which can reduce the risk of various cancers. However, the effects of END and ENL on ovarian cancer are not adequately documented. Methods We used in vitro assays on the ES-2 cell line to evaluate the inhibiting effects of END and ENL on ovarian cancer cell proliferation, invasion and migration ability and in vivo xenograft experiments on nude mice to validate the anticancer effects of END and ENL. Results The in vitro assays demonstrated that high-dose END and ENL could obviously inhibit ovarian malignant properties, including cancerous proliferation, invasion, and metastasis. Compared to END, ENL behaved in a better time-dose dependent manner on the cancer cells. The in vivo experiments showed that END (1 mg/kg), ENL (1 mg/kg) and ENL (0.1 mg/kg) suppressed tumor markedly, and there were statistically significant differences between the experimental and control groups in tumor weight and volume. Compared to END, which have serious side effects to the animals at high concentration such as 1 mg/kg, ENL had higher anticancer activities and less side effects in the animals than END at the same concentrations, so it would be a better candidate for drug development. Conclusion END and ENL both have potent inhibitory effects on ovarian cancer but ENL possesses a more effective anti-cancer capability and less side effects than END. Findings in this work provide novel insights into ovarian cancer therapeutics with phytoestrogens and encourage their clinical applications.
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    Fusobacterium nucleatum upregulates MMP7 to promote metastasis-related characteristics of colorectal cancer cell via activating MAPK(JNK)-AP1 axis
    (2023-10-09) Ou, Suwen; Chen, Haipeng; Wang, Hufei; Ye, Jinhua; Liu, Huidi; Tao, Yangbao; Ran, Songlin; Mu, Xiaoqin; Liu, Fangzhou; Zhu, Shuang; Luo, Kangjia; Guan, Zilong; Jin, Yinghu; Huang, Rui; Song, Yanni; Liu, Shu-lin
    Abstract Background Colorectal cancer (CRC) is the third most common malignant tumor. Fusobacterium nucleatum (F. nucleatum) is overabundant in CRC and associated with metastasis, but the role of F. nucleatum in CRC cell migration and metastasis has not been fully elucidated. Methods Differential gene analysis, protein−protein interaction, robust rank aggregation analysis, functional enrichment analysis, and gene set variation analysis were used to figure out the potential vital genes and biological functions affected by F. nucleatum infection. The 16S rDNA sequencing and q-PCR were used to detect the abundance of F. nucleatum in tissues and stools. Then, we assessed the effect of F. nucleatum on CRC cell migration by wound healing and transwell assays, and confirmed the role of Matrix metalloproteinase 7 (MMP7) induced by F. nucleatum in cell migration. Furthermore, we dissected the mechanisms involved in F. nucleatum induced MMP7 expression. We also investigated the MMP7 expression in clinical samples and its correlation with prognosis in CRC patients. Finally, we screened out potential small molecular drugs that targeted MMP7 using the HERB database and molecular docking. Results F. nucleatum infection altered the gene expression profile and affected immune response, inflammation, biosynthesis, metabolism, adhesion and motility related biological functions in CRC. F. nucleatum was enriched in CRC and promoted the migration of CRC cell by upregulating MMP7 in vitro. MMP7 expression induced by F. nucleatum infection was mediated by the MAPK(JNK)-AP1 axis. MMP7 was highly expressed in CRC and correlated with CMS4 and poor clinical prognosis. Small molecular drugs such as δ-tocotrienol, 3,4-benzopyrene, tea polyphenols, and gallic catechin served as potential targeted therapeutic drugs for F. nucleatum induced MMP7 in CRC. Conclusions Our study showed that F. nucleatum promoted metastasis-related characteristics of CRC cell by upregulating MMP7 via MAPK(JNK)-AP1 axis. F. nucleatum and MMP7 may serve as potential therapeutic targets for repressing CRC advance and metastasis.
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    Genetic boundaries delineate the potential human pathogen Salmonella bongori into discrete lineages: divergence and speciation
    (2019-12-04) Wang, Xiaoyu; Zhu, Songling; Zhao, Jian-Hua; Bao, Hong-Xia; Liu, Huidi; Ding, Tie-Min; Liu, Gui-Rong; Li, Yong-Guo; Johnston, Randal N; Cao, Feng-Lin; Tang, Le; Liu, Shu-Lin
    Abstract Background Salmonella bongori infect mainly cold-blooded hosts, but infections by S. bongori in warm-blooded hosts have been reported. We hypothesized that S. bongori might have diverged into distinct phylogenetic lineages, with some being able to infect warm-blooded hosts. Results To inspect the divergence status of S. bongori, we first completely sequenced the parakeet isolate RKS3044 and compared it with other sequenced S. bongori strains. We found that RKS3044 contained a novel T6SS encoded in a pathogenicity island-like structure, in addition to a T6SS encoded in SPI-22, which is common to all S. bongori strains so far reported. This novel T6SS resembled the SPI-19 T6SS of the warm-blooded host infecting Salmonella Subgroup I lineages. Genomic sequence comparisons revealed different genomic sequence amelioration events among the S. bongori strains, including a unique CTAG tetranucleotide degeneration pattern in RKS3044, suggesting non-overlapping gene pools between RKS3044 and other S. bongori lineages/strains leading to their independent accumulation of genomic variations. We further proved the existence of a clear-cut genetic boundary between RKS3044 and the other S. bongori lineages/strains analyzed in this study. Conclusions The warm-blooded host-infecting S. bongori strain RKS3044 has diverged with distinct genomic features from other S. bongori strains, including a novel T6SS encoded in a previously not reported pathogenicity island-like structure and a unique genomic sequence degeneration pattern. These findings alert cautions about the emergence of new pathogens originating from non-pathogenic ancestors by acquiring specific pathogenic traits.
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    KAZN as a diagnostic marker in ovarian cancer: a comprehensive analysis based on microarray, mRNA-sequencing, and methylation data
    (2022-06-16) Zhu, Songling; Bao, Hongxia; Zhang, Meng-Chun; Liu, Huidi; Wang, Yao; Lin, Caiji; Zhao, Xingjuan; Liu, Shu-Lin
    Abstract Background Ovarian cancer (OC) is among the deadliest malignancies in women and the lack of appropriate markers for early diagnosis leads to poor prognosis in most cases. Previous studies have shown that KAZN is involved in multiple biological processes during development, such as cell proliferation, differentiation, and apoptosis, so defects or aberrant expression of KAZN might cause queer cell behaviors such as malignancy. Here we evaluated the KAZN expression and methylation levels for possible use as an early diagnosis marker for OC. Methods We used data from Gene Expression Omnibus (GEO) microarrays, The Cancer Genome Atlas (TCGA), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) to investigate the correlations between KAZN expression and clinical characteristics of OC by comparing methylation levels of normal and OC samples. The relationships among differentially methylated sites in the KAZN gene, corresponding KAZN mRNA expression levels and prognosis were analyzed. Results KAZN was up-regulated in ovarian epithelial tumors and the expression of KAZN was correlated with the patients’ survival time. KAZN CpG site cg17657618 was positively correlated with the expression of mRNA and the methylation levels were significantly differential between the group of stage “I and II” and the group of stage “III and IV”. This study also presents a new method to classify tumor and normal tissue in OC using DNA methylation pattern in the KAZN gene body region. Conclusions KAZN was involved in ovarian cancer pathogenesis. Our results demonstrate a new direction for ovarian cancer research and provide a potential diagnostic biomarker as well as a novel therapeutic target for clinical application.