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Comprehensive Analysis of Estrogen Receptor 1 Dysregulation in liver hepatocellular carcinoma: Implications for Prognosis and Therapeutic Targeting - A Secondary Publication

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Proceedings of Anticancer Research 2024年第3期8卷 51-59页

作者： Syed Hussain Raza Yasir Hameed Department of Biochemistry and Biotechnology The Islamia University of BahawalpurBahawalpurPakistan

The study investigates the expression pattern and regulatory mechanisms of estrogen receptor 1 (ESR1) in liver hepatocellular carcinoma (LIHC) through comprehensive bioinformatics analysis. Utilizing UALCAN and GEPIA2 databases, significant down-regulation of ESR1 expression is observed in LIHC samples compared to normal controls, indicating its potential role in tumor progression. Further analysis reveals consistent down-regulation across different clinical variables including patient age, gender, race, and various stages of LIHC, affirming the regulatory role of ESR1 in tumor development and progression. Additionally, promoter methylation analysis demonstrates hypermethylation of ESR1 in LIHC samples, negatively correlating with its expression. This association persists across different clinical parameters, emphasizing the inverse relationship between ESR1 methylation and expression levels. Survival analysis indicates that up- regulation of ESR1 is associated with better overall survival, suggesting its potential as a prognostic biomarker in LIHC. Furthermore, genetic mutation analysis using cBioPortal reveals a spectrum of alterations in ESR1, including amplification, missense mutation, deep deletion, splice mutation, and truncating mutation, highlighting the genetic complexity of ESR1 in LIHC. These findings collectively contribute to a deeper understanding of ESR1 dysregulation in LIHC and its clinical implications as a potential therapeutic target and prognostic marker.

关键词： Estrogen receptor 1 liver hepatocellular carcinoma Biomarker Prognosis

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Pharmacologically targeting molecular motor promotes mitochondrial fission for anti-cancer

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Acta Pharmaceutica Sinica B 2021年第7期11卷 1853-1866页

作者： Yi Qian Meimei Zhao Qinghua Han Jingkang Wang Lixi Liao Heng Yang Dan Liu Pengfei Tu Hong Liang Kewu Zeng State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Proteomics Laboratory Medical and Healthy Analytical CenterPeking University Health Science CenterBeijing 100191China

Mitochondrial shape rapidly changes by dynamic balance of fusion and fission to adjust to constantly changing energy demands of cancer *** dynamics balance is exactly regulated by molecular motor consisted of myosin and actin cytoskeleton ***,targeting myosin eactin molecular motor is considered as a promising strategy for *** this study,we performed a proof-of-concept study with a natural-derived small-molecule J13 to test the feasibility of anti-cancer therapeutics via pharmacologically targeting molecular ***,we found J13 could directly target myosin-9(MYH9)eactin molecular motor to promote mitochondrial fission progression,and markedly inhibited cancer cells survival,proliferation and *** study revealed that J13 impaired MYH9 eactin interaction to inactivate molecular motor,and caused a cytoskeleton-dependent mitochondrial dynamics ***,stable isotope labeling with amino acids in cell culture(SILAC)technology-coupled with pulldown analysis identified HSPA9 as a crucial adaptor protein connecting MYH9 eactin molecular motor to mitochondrial *** together,we reported the first natural small-molecule directly targeting MYH9 eactin molecular motor for anti-cancer translational ***,our study also proved the conceptual practicability of pharmacologically disrupting mitochondrial fission/fusion dynamics in human cancer therapy.

关键词： Anti-cancer liver hepatocellular carcinoma Mitochondrial fission Small molecule Target identification Molecular motor MYH9 HSPA9

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Trans-arterial gene therapy for hepatocellular carcinoma in a rabbit model

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World Journal of Gastroenterology 2007年第14期13卷 2113-2117页

作者： Tao Gu Cai-Xia Li Yan Feng Qian Wang Chun-Hai Li Chuan-Fu Li Department of Radiology Qilu Hospital of Shandong University Jinan 250012 Shandong Province China

AIM： To study the effect of adenovirus （Ad）-p53 gene therapy on hepatocellular carcinoma （HCC） in a rabbit model.METHODS： VX2 tumor was grown in the liver of 24rabbits. Animals were divided into four groups： group A receiving trans-arterial gene therapy （Ad-p53） only,group B receiving combined Ad-p53 therapy and transarterial embolization （lipiodol）, group C receiving transarterial chemoembolization （lipiodol ＋ mitomycin C）,control group （D） receiving sodium chloride. Tumor volume （V1） was measured by using MRI （d 13）.Interventional procedure was applied （d 14）.Tumor volume （V2） was assessed by MRT （d 21） and the mean ratio （V2/V1） was calculated. After the second MRI,specimens of the liver were abstained and examined immunohistochemically using mutant-type p53 *** positive expression was scored.RESULTS： Compared with control group （（^-x） = 3.14± 0.64）, therapeutic groups all showed a significant decrease in the tumor growth ratio （P 〈 0.05）. A slight difference was found between group A （（^-x） =2.35 ±0.59） and group B （（^-x） = 1.75 ± 0.28）（P = 0.048）. Nostatistically significant difference was observed between group B and group C （（^-x） = 2.00 ± 0.44）. The positive expression rate of mutant-type p53 was the lowest in group B and significantly different between group A and group C （P 〈 0.05）.Compared to the control subjects, groups A and C both showed a decrease in the expression of mutant-type p53, but there was no significant difference between them.CONCLUSION： Trans-arterial Ad-p53 gene therapy can reduce tumor growth of HCC in rabbit model.

关键词： liver hepatocellular carcinoma Trans-arterial chemoembolization Gene therapy

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Spindle and Kinetochore-associated Family Genes are Prognostic and Predictive Biomarkers in hepatocellular carcinoma

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Journal of Clinical and Translational Hepatology 2022年第4期10卷 627-641页

作者： Chenhui Cai Ying Zhang Xu Hu Sizhen Yang Jiawen Ye Zihan Wei Tongwei Chu Department of Orthopedics Xinqiao HospitalThird Military Medical University(Army Medical University)ChongqingChina

Background and Aims:hepatocellular carcinoma(HCC)is one of the most frequent malignant *** and kinetochore-associated(SKA)family genes are essential for the maintenance of the metaphase plate and spindle checkpoint silencing during *** studies have indicated that dysregulation of SKA family genes induces tumorigenesis,tumor progression,and chemoresistance via modulation of cell cycle and DNA ***,the differential transcription of SKAs in the context of HCC and its prognostic significance has not been ***:Bioinformatics analyses were performed using TCGA,ONCOMINE,HCCDB,Kaplan-Meier plotter,STRING,GEPIA ***-PCR,western blot,and functional as-says were utilized for in vitro ***:We found remarkable upregulation of transcripts of SKA family genes in HCC samples compared with normal liver samples on bioinformatics analyses and in vitro ***-action analysis and enrichment analysis showed that SKA family members were mainly related to microtubule motor activity,mitosis,and cell ***-infiltration analysis showed a correlation of all SKA family genes with various immune cell subsets,especially T helper 2(Th2)***-scriptional levels of SKA family members were positively as-sociated with histologic grade,T stage,andα-fetoprotein in HCC *** operating characteristic curve analy-sis demonstrated a strong predictive ability of SKA1/2/3 for *** expression of these SKAs was associated with unfavorable overall survival,progression-free survival,and disease-specific *** Cox proportional hazards regression analyses,SKA1 upregulation and pathological staging were independent predictors of overall survival and disease-specific survival of HCC ***,clinical tissue microarray validation and in vitro functional assays revealed SKA1 acts an important regulatory role in tumor malignant ***:SKA family members may potentially serve

关键词： Spindle and kinetochore-associated genes liver hepatocellular carcinoma Prognostic value Immune infiltration Bioinformatics analysis

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