中文｜English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 37 Issue 2
Mar.  2021
Turn off MathJax
Article Contents
Article Navigation >  Journal of Clinical Hepatology  > 2021  >  37(2): 364-369

Role of differential expression and regulatory mechanism of miR-152-3p target proteins in the recurrence of hepatocellular carcinoma

DOI: 10.3969/j.issn.1001-5256.2021.02.023
  • 1.

    School of Clinical Medicine, Southwest Medical University, Luzhou, Sichuan 646000, China

  • 2a.

    Department of Clinical Laboratory, The General Hospital of Western Theater Command, Chengdu 610083, China

  • 2b.

    Department of Gastroenterology, The General Hospital of Western Theater Command, Chengdu 610083, China

  • 2c.

    Department of Oncology, The General Hospital of Western Theater Command, Chengdu 610083, China

  • Received Date: 2020-09-04
  • Accepted Date: 2020-10-19
  • Published Date: 2021-02-20
    Abstract
  •   Objective  To investigate the difference in protein expression between hepatocellular carcinoma (HCC) patients with recurrence and those with good prognosis, the differential expression and regulatory mechanism of miR-152-3p target proteins, and the role of miR-152-3p in the recurrence of HCC.  Methods  TMT-labeled proteomic sequencing and RT-PCR were used to measure the expression of proteins and the expression of miR-152-3p in the HCC tissue of six patients with recurrence at 2 years after HCC resection and six patients with good prognosis at 5 years. Six databases were used to analyze the target genes of miR-152-3p, and Gene Ontology, DAVID, and REACTOME databases were used to perform target gene screening, enrichment annotation, and signal transduction pathway enrichment analysis. Gene mutation frequency and survival curve analysis were performed for the target genes of miR-152-3p to verify the role of miR-152-3p target genes in patients with HCC recurrence. The independent samples t-test was used for comparison of continuous data between two groups, and a Kaplan-Meier analysis was performed to investigate the survival rates of liver-related genes.  Results  Compared with the patients with HCC recurrence, the patients with good prognosis after HCC resection had a significantly higher transcriptional expression level of miR-152-3p in HCC tissue (P < 0.05). The results of protein sequencing showed that there were 365 differentially expressed proteins in HCC tissue between the patients with good prognosis and the patients with recurrence, and the analysis of HCC recurrence databases showed that 17 proteins were regulated by miR-152-3p. Further analysis of the signaling pathways showed that the function of the 17 target genes regulated by miR-152-3p was enriched in the translation and regulation of mitochondria and ribosome, and multiple enrichment revealed that six target genes were closely associated with mitochondrial respiratory chain complex, i.e., AKAP1, FOXRED1, MRPL28, MRPL50, SHC1, and STAU1. Gene mutation frequency and survival curve analysis showed that the loss or weakening of the function of mitochondrial respiratory chain-related target proteins seriously affected the prognosis and survival rate of patients.  Conclusion  There is a significant difference in the expression of miR-152-3p in HCC tissue between patients with good prognosis and those with recurrence after HCC resection, and miR-152-3p may lead to the recurrence of HCC by regulating the target genes AKAP1, FOXRED1, MRPL28, MRPL50, SHC1, and STAU1, acting on the mitochondrial respiratory chain, and affecting the oxidative respiratory function of cells.

     

    • FullText(HTML)
  • loading
    • References(20)
  • [1]
    DUTTA R, MAHATO RI. Recent advances in hepatocellular carcinoma therapy[J]. Pharmacol Ther, 2017, 173(5): 106-117.
    [2]
    ZHANG Z, MA L, GOSWAMI S, et al. Landscape of infiltrating B cells and their clinical significance in human hepatocellular carcinoma[J]. OncoImmunology, 2019, 8(4): 1-11.
    [3]
    ZHAO ZJ, HU Y, SHEN XH, et al. HBx represses RIZ1 expression by DNA methyltransferase 1 involvement in decreased miR-152 in hepatocellular carcinoma[J]. Oncol Rep, 2017, 37(5): 2811. DOI: 10.3892/or.2017.5518
    [4]
    DUAN YF, ZHAO QX, JING X. Effect of long non-coding RNAs on glycolytic pathway in primary liver cancer and related mechanisms[J]. J Clin Hepatol, 2019, 35(6): 1374-1376. (in Chinese) DOI: 10.3969/j.issn.1001-5256.2019.06.043

    段艺菲, 赵清喜, 荆雪.长链非编码RNA对原发性肝癌中糖酵解途径的影响机制[J].临床肝胆病杂志, 2019, 35(6): 1374-1376. DOI: 10.3969/j.issn.1001-5256.2019.06.043
    [5]
    DING J, DUAN BW, DI L. Expression and mechanism of microRNA and Na+/H+ exchanger regulatory factor 1 on hepatocellular carcinoma[J/CD]. Chin J Liver Dis (Electronic Version), 2020, 12(3): 59-64.(in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-GZBZ202003015.htm

    丁兢, 段斌炜, 邸亮.微小RNA-320a和钠氢交换调控因子1在肝细胞癌中的表达及机制[J/CD].中国肝脏病杂志(电子版), 2020, 12(3): 59-64. https://www.cnki.com.cn/Article/CJFDTOTAL-GZBZ202003015.htm
    [6]
    QU ZN, LIN L, ZHONG W, et al. Meta-analysis of value of circulating microRNA 122 on diagnosis of hepatocellular carcinoma[J/CD]. Chin J Liver Dis (Electronic Version), 2020, 12(3): 23-28.(in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-GZBZ202003007.htm

    屈振南, 林霖, 钟伟, 等.循环微小RNA-122诊断肝细胞癌的Meta分析[J/CD].中国肝脏病杂志(电子版), 2020, 12(3): 23-28. https://www.cnki.com.cn/Article/CJFDTOTAL-GZBZ202003007.htm
    [7]
    ZHOU JJ, ZHANG YJ, QI YH, et al. MicroRNA-152 inhibits tumor cell growth by directly targeting RTKN in hepatocellular carcinoma[J]. Oncol Rep, 2017, 37(2): 1227. DOI: 10.3892/or.2016.5290
    [8]
    MIQUELESTORENA-STANDLEY E, TALLET A, COLLIN C, et al. Interest of variations in microRNA-152 and-122 in a series of hepatocellular carcinomas related to hepatitis C virus infection[J]. Hepatol Res, 2018, 48(7): 566-573. DOI: 10.1111/hepr.12915
    [9]
    BILIC′ P, GUILLEMIN N, KOVACˇEVIC′ A, et al. Serum proteome profiling in canine idiopathic dilated cardiomyopathy using TMT-based quantitative proteomics approach[J]. J Proteomics, 2018, 179: 110-121. DOI: 10.1016/j.jprot.2018.03.007
    [10]
    CHANG K, JIANG ZY, REN JL, et al. Bioinformatics prediction of miR-130b-3p target genes associated with diabetic nephropathy[J]. J Chongqing Med Univ, 2018, 43(6): 788-792. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-ZQYK201806011.htm

    常凯, 江忠勇, 任俊龙, 等.糖尿病肾病相关miR-130b-3p靶点的生物信息学预测[J].重庆医科大学学报, 2018, 43(6): 788-792. https://www.cnki.com.cn/Article/CJFDTOTAL-ZQYK201806011.htm
    [11]
    CHEN L, ZHANG YH, WANG SP, et al. Prediction and analysis of essential genes using the enrichments of gene ontology and KEGG pathways[J]. PLoS One, 2017, 12(9): e0184129. DOI: 10.1371/journal.pone.0184129
    [12]
    WANG F, YING H, HE B, et al. Circulating miR-148/152 family as potential biomarkers in hepatocellular carcinoma[J]. Tumour Biol, 2016, 37(4): 4945-4953. DOI: 10.1007/s13277-015-4340-z
    [13]
    HUANG J, WANG Y, GUO Y, et al. Down-regulated microRNA-152 induces aberrant DNA methylation in hepatitis B virus-related hepatocellular carcinoma by targeting DNA methyltransferase 1[J]. Hepatology, 2010, 52(1): 60-70. DOI: 10.1002/hep.23660
    [14]
    DANG YW, ZENG J, HE RQ, et al. Effects of miR-152 on cell growth inhibition, motility suppression and apoptosis induction in hepatocellular carcinoma cells[J]. Asian Pac J Cancer Prev, 2014, 15(12): 4969-4976. DOI: 10.7314/APJCP.2014.15.12.4969
    [15]
    IRYNA K, VOLODYMYR T, ALINE DC, et al. MicroRNA-152-mediated dysregulation of hepatic transferrin receptor 1 in liver carcinogenesis[J]. Oncotarget, 2016, 7(2): 1276-1287. DOI: 10.18632/oncotarget.6004
    [16]
    FORMOSA LE, MASAKAZU M, FRAZIER AE, et al. Characterization of mitochondrial FOXRED1 in the assembly of respiratory chain complex I[J]. Hum Mol Genet, 2015, 24(10): 2952-2965. DOI: 10.1093/hmg/ddv058
    [17]
    DAGDA RK, GUSDON AM, PIEN I, et al. Mitochondrially localized PKA reverses mitochondrial pathology and dysfunction in a cellular model of Parkinson's disease[J]. Cell Death Differ, 2011, 18(12): 1914-1923. DOI: 10.1038/cdd.2011.74
    [18]
    YU J, ZHANG Y, ZHOU DX, et al. Higher expression of A-kinase anchoring-protein 1 predicts poor prognosis in human hepatocellular carcinoma[J]. Oncol Lett, 2018, 16(1): 131-136.
    [19]
    JIANG ZJ, CHEN J, LI LQ. Research progress of long non-coding RNA in the invasion and metastasis of hepatocellular carcinoma[J]. J Med Postgraduates, 2019, 32(7): 765-770. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-JLYB201907020.htm

    蒋志俊, 陈洁, 黎乐群.长链非编码RNA在肝癌侵袭转移中的研究进展[J].医学研究生学报, 2019, 32(7): 765-770. https://www.cnki.com.cn/Article/CJFDTOTAL-JLYB201907020.htm
    [20]
    ZHANG XC, LI B. Towards understanding the mechanisms of proton pumps in Complex-Ⅰ of the respiratory chain[J]. Biophy Rep, 2019, 5(5-6): 219-234. DOI: 10.1007/s41048-019-00094-7
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(4)  / Tables(5)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (512) PDF downloads(28) Cited by()
    Proportional views
    Related
        

    The first journal specializing in hepatobiliary and pancreatic diseases in China

    Supervisor：Ministry of Education of the People's Republic of China

    Sponsor：Jilin University

    Academic Support: Chinese Society of Hepatology，Chinese Medical Association

    Address: 461 Xinjiang Road, Changchun

    Submit：0431-88782044

    Peer review：0431-88783542

    Email：lcgdb@vip.163.com

    About Journal

    Submission Guideline

    Journal Online

    Hepatobiliary College

    Guidelines

    YesterdayIP[]YesterdayPV[]TodayIP[]TodayPV[]Online[]

    Website Design © 2020 Editorial Board of Journal of Clinical Hepatology 吉ICP备10000617号-1 Supported by: Beijing Renhe Information Technology Co. Ltd  

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return