中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 37 Issue 4
Apr.  2021
Turn off MathJax
Article Contents

Mechanism of action of forkhead box transcription factors in hepatocellular carcinoma and their prospects as treatment targets

DOI: 10.3969/j.issn.1001-5256.2021.04.044
  • Received Date: 2020-09-18
  • Accepted Date: 2020-11-05
  • Published Date: 2021-04-20
  • Hepatocellular carcinoma (HCC) is one of the most common malignant cancers and has high incidence and mortality rates and poor prognosis. Forkhead box (FOX) transcription factor family can regulate cell growth, differentiation, and tissue development and plays an important role in tumor. This article reviews the association of the molecular expression of the FOX family with the development, progression, and prognosis of HCC and analyzes the mechanism of action of FOX in the progression of HCC. It is pointed out that FOX family is expected to become a new target for HCC treatment.

     

  • loading
  • [1]
    YUAN Z, YE M, QIE J, et al. FOXA1 promotes cell proliferation and suppresses apoptosis in HCC by directly regulating miR-212-3p/FOXA1/AGR2 signaling pathway[J]. Onco Targets Ther, 2020, 13: 5231-5240. DOI: 10.2147/OTT.S252890
    [2]
    WANG Y, YANG L, CHEN T, et al. A novel lncRNA MCM3AP-AS1 promotes the growth of hepatocellular carcinoma by targeting miR-194-5p/FOXA1 axis[J]. Mol Cancer, 2019, 18(1): 28. DOI: 10.1186/s12943-019-0957-7
    [3]
    LIU J, YU Z, XIAO Y, et al. Coordination of FOXA2 and SIRT6 suppresses the hepatocellular carcinoma progression through ZEB2 inhibition[J]. Cancer Manag Res, 2018, 10: 391-402. DOI: 10.2147/CMAR.S150552
    [4]
    WANG LB, WANG X, CAO J, et al. Inhibitory effect of FOXA2 on proliferation and tumorigenesis of hepatocellular carcinoma cells[J]. J Pract Med, 2019, 35(4): 546-551. (in Chinese) DOI: 10.3969/j.issn.1006-5725.2019.04.010

    王立斌, 王曦, 曹佳, 等. 叉头框蛋白A2对肝癌细胞增殖和成瘤的抑制作用[J]. 实用医学杂志, 2019, 35(4): 546-551. DOI: 10.3969/j.issn.1006-5725.2019.04.010
    [5]
    LIANG WC, REN JL, WONG CW, et al. LncRNA-NEF antagonized epithelial to mesenchymal transition and cancer metastasis via cis-regulating FOXA2 and inactivating Wnt/β-catenin signaling[J]. Oncogene, 2018, 37(11): 1445-1456. DOI: 10.1038/s41388-017-0041-y
    [6]
    LI Z, TUTEJA G, SCHUG J, et al. Foxa1 and Foxa2 are essential for sexual dimorphism in liver cancer[J]. Cell, 2012, 148(1-2): 72-83. DOI: 10.1016/j.cell.2011.11.026
    [7]
    TAKASHIMA Y, HORISAWA K, UDONO M, et al. Prolonged inhibition of hepatocellular carcinoma cell proliferation by combinatorial expression of defined transcription factors[J]. Cancer Sci, 2018, 109(11): 3543-3553. DOI: 10.1111/cas.13798
    [8]
    CHENG Z, HE Z, CAI Y, et al. Conversion of hepatoma cells to hepatocyte-like cells by defined hepatocyte nuclear factors[J]. Cell Res, 2019, 29(2): 124-135. DOI: 10.1038/s41422-018-0111-x
    [9]
    XIA L, HUANG W, TIAN D, et al. Overexpression of forkhead box C1 promotes tumor metastasis and indicates poor prognosis in hepatocellular carcinoma[J]. Hepatology, 2013, 57(2): 610-624. DOI: 10.1002/hep.26029
    [10]
    HUANG W, CHEN Z, ZHANG L, et al. Interleukin-8 induces expression of FOXC1 to promote transactivation of CXCR1 and CCL2 in hepatocellular carcinoma cell lines and formation of metastases in mice[J]. Gastroenterology, 2015, 149(4): 1053-1067.e14. DOI: 10.1053/j.gastro.2015.05.058
    [11]
    SHIMODA Y, UBUKATA Y, HANDA T, et al. High expression of forkhead box protein C2 is associated with aggressive phenotypes and poor prognosis in clinical hepatocellular carcinoma[J]. BMC Cancer, 2018, 18(1): 597. DOI: 10.1186/s12885-018-4503-6
    [12]
    LIANG C, ZHAO J, GE H, et al. Clinicopathological and prognostic significance of FoxM1 in hepatocellular carcinoma patients: A meta-analysis[J]. Onco Targets Ther, 2018, 11: 3561-3571. DOI: 10.2147/OTT.S155541
    [13]
    KOPANJA D, PANDEY A, KIEFER M, et al. Essential roles of FoxM1 in Ras-induced liver cancer progression and in cancer cells with stem cell features[J]. J Hepatol, 2015, 63(2): 429-436. DOI: 10.1016/j.jhep.2015.03.023
    [14]
    FILLIOL A, SCHWABE RF. FoxM1 induces CCl2 secretion from hepatocytes triggering hepatic inflammation, injury, fibrosis, and liver cancer[J]. Cell Mol Gastroenterol Hepatol, 2020, 9(3): 555-556. DOI: 10.1016/j.jcmgh.2020.01.002
    [15]
    LI Y, LU L, TU J, et al. Reciprocal regulation between forkhead box M1/NF-κB and methionine adenosyltransferase 1a drives liver cancer[J]. Hepatology, 2020, 72(5): 1682-1700. DOI: 10.1002/hep.31196
    [16]
    HU G, YAN Z, ZHANG C, et al. FOXM1 promotes hepatocellular carcinoma progression by regulating KIF4A expression[J]. J Exp Clin Cancer Res, 2019, 38(1): 188. DOI: 10.1186/s13046-019-1202-3
    [17]
    WANG Y, WANG H, YAN Z, et al. The critical role of dysregulated Hh-FOXM1-TPX2 signaling in human hepatocellular carcinoma cell proliferation[J]. Cell Commun Signal, 2020, 18(1): 116. DOI: 10.1186/s12964-020-00628-4
    [18]
    SHANG R, WANG M, DAI B, et al. Long noncoding RNA SLC2A1-AS1 regulates aerobic glycolysis and progression in hepatocellular carcinoma via inhibiting the STAT3/FOXM1/GLUT1 pathway[J]. Mol Oncol, 2020, 14(6): 1381-1396. DOI: 10.1002/1878-0261.12666
    [19]
    LIU S, QIU J, HE G, et al. LncRNA MALAT1 acts as a miR-125a-3p sponge to regulate FOXM1 expression and promote hepatocellular carcinoma progression[J]. J Cancer, 2019, 10(26): 6649-6659. DOI: 10.7150/jca.29213
    [20]
    WEI Y, WANG Z, ZONG Y, et al. LncRNA MFI2-AS1 promotes HCC progression and metastasis by acting as a competing endogenous RNA of miR-134 to upregulate FOXM1 expression[J]. Biomed Pharmacother, 2020, 125: 109890. DOI: 10.1016/j.biopha.2020.109890
    [21]
    SHI H, FANG R, LI Y, et al. The oncoprotein HBXIP suppresses gluconeogenesis through modulating PCK1 to enhance the growth of hepatoma cells[J]. Cancer Lett, 2016, 382(2): 147-156. DOI: 10.1016/j.canlet.2016.08.025
    [22]
    JIANG J, LIU Z, GE C, et al. NK3 homeobox 1 (NKX3.1) up-regulates forkhead box O1 expression in hepatocellular carcinoma and thereby suppresses tumor proliferation and invasion[J]. J Biol Chem, 2017, 292(47): 19146-19159. DOI: 10.1074/jbc.M117.793760
    [23]
    LIN X, ZUO S, LUO R, et al. HBX-induced miR-5188 impairs FOXO1 to stimulate β-catenin nuclear translocation and promotes tumor stemness in hepatocellular carcinoma[J]. Theranostics, 2019, 9(25): 7583-7598. DOI: 10.7150/thno.37717
    [24]
    LU M, HARTMANN D, BRAREN R, et al. Oncogenic Akt-FOXO3 loop favors tumor-promoting modes and enhances oxidative damage-associated hepatocellular carcinogenesis[J]. BMC Cancer, 2019, 19(1): 887. DOI: 10.1186/s12885-019-6110-6
    [25]
    WANG H, ZHANG CZ, LU SX, et al. A coiled-coil domain containing 50 splice variant is modulated by serine/arginine-rich splicing factor 3 and promotes hepatocellular carcinoma in mice by the ras signaling pathway[J]. Hepatology, 2019, 69(1): 179-195. DOI: 10.1002/hep.30147
    [26]
    GONG C, AI J, FAN Y, et al. NCAPG promotes the proliferation of hepatocellular carcinoma through PI3K/AKT signaling[J]. Onco Targets Ther, 2019, 12: 8537-8552. DOI: 10.2147/OTT.S217916
    [27]
    YU X, GAO X, MAO X, et al. Knockdown of FOXO6 inhibits glycolysis and reduces cell resistance to paclitaxel in HCC cells via PI3K/Akt signaling pathway[J]. Onco Targets Ther, 2020, 13: 1545-1556. DOI: 10.2147/OTT.S233031
    [28]
    WANG X, SUN J, CUI M, et al. Downregulation of FOXP1 inhibits cell proliferation in hepatocellular carcinoma by inducing G1/S phase cell cycle arrest[J]. Int J Mol Sci, 2016, 17(9): 1501. DOI: 10.3390/ijms17091501
    [29]
    YAN X, ZHOU H, ZHANG T, et al. Downregulation of FOXP2 promoter human hepatocellular carcinoma cell invasion[J]. Tumour Biol, 2015, 36(12): 9611-9619. DOI: 10.1007/s13277-015-3701-y
    [30]
    XIAO WL. Mechanism of regularatory T cells in tumor immunity and the new strategy of treatment[J]. Chin J Cancer Biother, 2019, 26(12): 1387-1391. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-ZLSW201912015.htm

    肖文路. 调节性T细胞在肿瘤免疫中作用机制及治疗新策略的研究进展[J]. 中国肿瘤生物治疗杂志, 2019, 26(12): 1387-1391. https://www.cnki.com.cn/Article/CJFDTOTAL-ZLSW201912015.htm
    [31]
    SHI JY, MA LJ, ZHANG JW, et al. FOXP3 is a HCC suppressor gene and acts through regulating the TGF-β/Smad2/3 signaling pathway[J]. BMC Cancer, 2017, 17(1): 648. DOI: 10.1186/s12885-017-3633-6
    [32]
    ZHANG G, ZHANG G. Upregulation of FoxP4 in HCC promotes migration and invasion through regulation of EMT[J]. Oncol Lett, 2019, 17(4): 3944-3951. http://www.ncbi.nlm.nih.gov/pubmed/30930991
    [33]
    ZHAO ZG, WANG DQ, HU DF, et al. Decreased FOXF1 promotes hepatocellular carcinoma tumorigenesis, invasion, and stemness and is associated with poor clinical outcome[J]. Onco Targets Ther, 2016, 9: 1743-1752. http://www.ncbi.nlm.nih.gov/pubmed/27042124
    [34]
    SHI Z, LIU J, YU X, et al. Loss of FOXF2 expression predicts poor prognosis in hepatocellular carcinoma patients[J]. Ann Surg Oncol, 2016, 23(1): 211-217. DOI: 10.1245/s10434-015-4515-2
    [35]
    ZHENG X, LIN J, WU H, et al. Forkhead box (FOX) G1 promotes hepatocellular carcinoma epithelial-Mesenchymal transition by activating Wnt signal through forming T-cell factor-4/Beta-catenin/FOXG1 complex[J]. J Exp Clin Cancer Res, 2019, 38(1): 475. DOI: 10.1186/s13046-019-1433-3
    [36]
    ZHU X, LI ZG, YANG YZ, et al. Levels of FOXJ1 and NF-κB in hepatocellular carcinoma and its clinical significance[J]. Chin J Health Lab Technol, 2019, 29(15): 1863-1866. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-ZWJZ201915022.htm

    朱侠, 李治刚, 杨永志, 等. 叉头框转录因子J和核转录因子κB在肝细胞肝癌中的表达及其临床意义[J]. 中国卫生检验杂志, 2019, 29(15): 1863-1866. https://www.cnki.com.cn/Article/CJFDTOTAL-ZWJZ201915022.htm
    [37]
    JIN GZ, ZHANG Y, CONG WM, et al. Phosphoglucomutase 1 inhibits hepatocellular carcinoma progression by regulating glucose trafficking[J]. PLoS Biol, 2018, 16(10): e2006483. DOI: 10.1371/journal.pbio.2006483
    [38]
    CAO H, CHU X, WANG Z, et al. High FOXK1 expression correlates with poor outcomes in hepatocellular carcinoma and regulates stemness of hepatocellular carcinoma cells[J]. Life Sci, 2019, 228: 128-134. DOI: 10.1016/j.lfs.2019.04.068
    [39]
    LIN MF, YANG YF, PENG ZP, et al. FOXK2, regulted by miR-1271-5p, promotes cell growth and indicates unfavorable prognosis in hepatocellular carcinoma[J]. Int J Biochem Cell Biol, 2017, 88: 155-161. DOI: 10.1016/j.biocel.2017.05.019
    [40]
    LEE HA, CHU KB, MOON EK, et al. Sensitization to oxidative stress and G2/M cell cycle arrest by histone deacetylase inhibition in hepatocellular carcinoma cells[J]. Free Radic Biol Med, 2020, 147: 129-138. DOI: 10.1016/j.freeradbiomed.2019.12.021
    [41]
    EGAWA M, YOSHIDA Y, OGURA S, et al. Increased expression of Forkhead box M1 transcription factor is associated with clinicopathological features and confers a poor prognosis in human hepatocellular carcinoma[J]. Hepatol Res, 2017, 47(11): 1196-1205. DOI: 10.1111/hepr.12854
    [42]
    GARTEL AL. A new target for proteasome inhibitors: FoxM1[J]. Expert Opin Investig Drugs, 2010, 19(2): 235-242. DOI: 10.1517/13543780903563364
    [43]
    HE L, YANG X, CAO X, et al. Casticin induces growth suppression and cell cycle arrest through activation of FOXO3a in hepatocellular carcinoma[J]. Oncol Rep, 2013, 29(1): 103-108. DOI: 10.3892/or.2012.2076
    [44]
    WANG JG, ZHENG XX, ZENG GY, et al. Purified vitexin compound 1 induces apoptosis through activation of FOXO3a in hepatocellular carcinoma[J]. Oncol Rep, 2014, 31(1): 488-496. DOI: 10.3892/or.2013.2855
    [45]
    JIANG J, HUANG Z, CHEN X, et al. Trifluoperazine activates FOXO1-related signals to inhibit tumor growth in hepatocellular carcinoma[J]. DNA Cell Biol, 2017, 36(10): 813-821. DOI: 10.1089/dna.2017.3790
  • 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

    Article Metrics

    Article views (517) PDF downloads(37) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return