中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 40 Issue 9
Sep.  2024
Turn off MathJax
Article Contents

Expression of AU-rich element RNA-binding factor 1 in hepatocellular carcinoma and its value in prognostic evaluation

DOI: 10.12449/JCH240918
Research funding:

National Natural Science Foundation of China (General Program) (81572366);

Youth Innovation and Talent Cultivation Project of Shihezi University (CXPY202311)

More Information
  • Corresponding author: WANG Jingzhou, neil_wjz@163.com (ORCID: 0000-0002-7490-8076); CHEN Xiangmei, xm_chen6176@bjmu.edu.cn (ORCID: 0000-0003-0302-6866)
  • Received Date: 2024-01-24
  • Accepted Date: 2024-03-25
  • Published Date: 2024-09-25
  •   Objective  To investigate the effect of AU-rich element RNA-binding factor 1 (AUF1) on the proliferation, apoptosis, and migration abilities of hepatocellular carcinoma (HCC) cells and possible mechanisms, and to clarify the role and molecular mechanism of AUF1 in the progression of HCC.  Methods  The UALCAN and TCGA-HCC databases were used to analyze the expression of AUF1 in pan-cancer and investigate the association of the expression level of AUF1 with the clinicopathological features and prognosis of HCC patients. CCK-8 assay, cell apoptosis assay, and Transwell chamber assay were used to investigate the function of AUF1 at the cellular level, and RNA-seq assay was used to investigate transcriptome changes in HCC cells after AUF1 knockdown. The t-test was used for comparison of continuous data between two groups; the Kaplan-Meier method was used to plot survival curves, and the log-rank test was used for comparison of survival rates.  Results  There were abnormal mRNA and protein expression levels of AUF1 in various tumor tissues compared with normal tissue (P<0.05). The mRNA expression level of AUF1 was positively correlated with the degree of HCC malignancy and the poor prognosis of early-stage HCC (P<0.05). Compared with the control group, the overexpression of exogenous AUF1 in HCC cells promoted the proliferation of HCC cells and inhibited the apoptosis and migration of HCC cells, while AUF1 knockdown inhibited HCC cell proliferation and promoted the apoptosis and migration of HCC cells. The RNA-seq analysis showed that AUF1 knockdown mainly affected the Wnt/β-catenin pathway and downregulated the protein expression level of β-catenin.  Conclusion  The abnormal expression of AUF1 is associated with the prognosis of early-stage HCC, and AUF1 may exert an oncogenic effect by activating the Wnt signaling pathway.

     

  • loading
  • [1]
    SUNG H, FERLAY J, SIEGEL RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71( 3): 209- 249. DOI: 10.3322/caac.21660.
    [2]
    BLECHACZ B, MISHRA L. Hepatocellular carcinoma biology[J]. Recent Results Cancer Res, 2013, 190: 1- 20. DOI: 10.1007/978-3-642-16037-0_1.
    [3]
    CHEN CY, SHYU AB. AU-rich elements: Characterization and importance in mRNA degradation[J]. Trends Biochem Sci, 1995, 20( 11): 465- 470. DOI: 10.1016/s0968-0004(00)89102-1.
    [4]
    LIU H, ZHENG W, SONG Z. circDlgap4 alleviates cerebral ischaemic injury by binding to AUF1 to suppress oxidative stress and neuroinflammation[J]. Mol Neurobiol, 2022, 59( 5): 3218- 3232. DOI: 10.1007/s12035-022-02796-5.
    [5]
    CHEN LY, LINGNER J. AUF1/HnRNP D RNA binding protein functions in telomere maintenance[J]. Mol Cell, 2012, 47( 1): 1- 2. DOI: 10.1016/j.molcel.2012.06.031.
    [6]
    ULLMER W, SEMLER BL. Direct and indirect effects on viral translation and RNA replication are required for AUF1 restriction of enterovirus infections in human cells[J]. mBio, 2018, 9( 5): e01669- e01618. DOI: 10.1128/mBio.01669-18.
    [7]
    MOORE AE, CHENETTE DM, LARKIN LC, et al. Physiological networks and disease functions of RNA-binding protein AUF1[J]. Wiley Interdiscip Rev RNA, 2014, 5( 4): 549- 564. DOI: 10.1002/wrna.1230.
    [8]
    WU QC, LI JH, WANG B, et al. Significance of the expression levels of GPC-3 and AUF1 in cancer tissue in the evaluation of pathological stage and prognosis of patients with esophageal cancer[J]. Clin Misdiagnosis Mistherapy, 2023, 9( 10): 44- 48.

    吴其琛, 李俊海, 王博, 等. 癌组织中GPC-3、AUF1表达水平对食管癌患者病理分期及预后评估的意义[J]. 临床误诊误治, 2023, 9( 10): 44- 48.
    [9]
    CHANDRASHEKAR DS, BASHEL B, BALASUBRAMANYA SAH, et al. UALCAN: A portal for facilitating tumor subgroup gene expression and survival analyses[J]. Neoplasia, 2017, 19( 8): 649- 658. DOI: 10.1016/j.neo.2017.05.002.
    [10]
    CHANDRASHEKAR DS, KARTHIKEYAN SK, KORLA PK, et al. UALCAN: An update to the integrated cancer data analysis platform[J]. Neoplasia, 2022, 25: 18- 27. DOI: 10.1016/j.neo.2022.01.001.
    [11]
    ZHANG T, GUAN GW, ZHANG J, et al. E2F1-mediated AUF1 upregulation promotes HCC development and enhances drug resistance via stabilization of AKR1B10[J]. Cancer Sci, 2022, 113( 4): 1154- 1167. DOI: 10.1111/cas.15272.
    [12]
    KIM D, PERTEA G, TRAPNELL C, et al. TopHat2: Accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions[J]. Genome Biol, 2013, 14( 4): R36. DOI: 10.1186/gb-2013-14-4-r36.
    [13]
    LIAO Y, SMYTH GK, SHI W. featureCounts: An efficient general purpose program for assigning sequence reads to genomic features[J]. Bioinformatics, 2014, 30( 7): 923- 930. DOI: 10.1093/bioinformatics/btt656.
    [14]
    ROBINSON MD, MCCARTHY DJ, SMYTH GK. edgeR: A Bioconductor package for differential expression analysis of digital gene expression data[J]. Bioinformatics, 2010, 26( 1): 139- 140. DOI: 10.1093/bioinformatics/btp616.
    [15]
    YANG YZ, KANG P, GAO J, et al. AU-binding factor 1 expression was correlated with metadherin expression and progression of hepatocellular carcinoma[J]. Tumour Biol, 2014, 35( 3): 2747- 2751. DOI: 10.1007/s13277-013-1362-2.
    [16]
    DANG H, TAKAI A, FORGUES M, et al. Oncogenic activation of the RNA binding protein NELFE and MYC signaling in hepatocellular carcinoma[J]. Cancer Cell, 2017, 32( 1): 101- 114. e 8. DOI: 10.1016/j.ccell.2017.06.002.
    [17]
    JUNG YS, STRATTON SA, LEE SH, et al. TMEM9-v-ATPase activates Wnt/β-catenin signaling via APC lysosomal degradation for liver regeneration and tumorigenesis[J]. Hepatology, 2021, 73( 2): 776- 794. DOI: 10.1002/hep.31305.
    [18]
    LACHENMAYER A, ALSINET C, SAVIC R, et al. Wnt-pathway activation in two molecular classes of hepatocellular carcinoma and experimental modulation by sorafenib[J]. Clin Cancer Res, 2012, 18( 18): 4997- 5007. DOI: 10.1158/1078-0432.CCR-11-2322.
    [19]
    QU JY, LIU XT, LI J, et al. AKR1B10 promotes proliferation of breast cancer cells by activating Wnt/β-catenin pathway[J]. Chin J Cell Mol Immunol, 2019, 35( 12): 1094- 1100.

    屈佳肴, 刘香婷, 李佳, 等. 醛酮还原酶家族1成员B10(AKR1B10)通过激活Wnt/β-catenin通路促进乳腺癌细胞增殖[J]. 细胞与分子免疫学杂志, 2019, 35( 12): 1094- 1100.
  • 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(6)

    Article Metrics

    Article views (114) PDF downloads(11) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return