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Article

Cooperative antiproliferative effect of coordinated ectopic expression of DLC1 tumor suppressor protein and silencing of MYC oncogene expression in liver cancer cells: Therapeutic implications

  • Authors:
    • Xuyu Yang
    • Xiaoling Zhou
    • Paul Tone
    • Marian E. Durkin
    • Nicholas C. Popescu
  • View Affiliations / Copyright

    Affiliations: Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 2089‑4262, USA, Department of Medicine, Richmond University Medical Center, Staten Island, NY 10310, USA
  • Pages: 1591-1596
    |
    Published online on: June 24, 2016
       https://doi.org/10.3892/ol.2016.4781
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Abstract

Human hepatocellular carcinoma (HCC) is one of the most common types of cancer and has a very poor prognosis; thus, the development of effective therapies for the treatment of advanced HCC is of high clinical priority. In the present study, the anti‑oncogenic effect of combined knockdown of c‑Myc expression and ectopic restoration of deleted in liver cancer 1 (DLC1) expression was investigated in human liver cancer cells. Expression of c‑Myc in human HCC cells was knocked down by stable transfection with a Myc‑specific short hairpin (sh) RNA vector. DLC1 expression in Huh7 cells was restored by adenovirus transduction, and the effects of DLC1 expression and c‑Myc knockdown on Ras homolog gene family, member A (RhoA) levels, cell proliferation, soft agar colony formation and cell invasion were measured. Downregulation of c‑Myc or re‑expression of DLC1 led to a marked reduction in RhoA levels, which was associated with decreases in cell proliferation, soft agar colony formation and invasiveness; this inhibitory effect was augmented with a combination of DLC1 transduction and c‑Myc suppression. To determine whether liver cell‑specific delivery of DLC1 was able to enhance the inhibitory effect of c‑Myc knockdown on tumor growth in vivo, DLC1 vector DNA complexed with galactosylated polyethylene glycol‑linear polyethyleneimine was administered by tail vein injection to mice bearing subcutaneous xenografts of Huh7 cells transfected with shMyc or control shRNA. A cooperative inhibitory effect of DLC1 expression and c‑Myc knockdown on the growth of Huh7‑derived tumors was observed, suggesting that targeted liver cell delivery of DLC1 and c‑Myc shRNA may serve as a possible gene therapy modality for the treatment of human HCC.
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1 

Tinkle CL and Haas-Kogen D: Hepatocellular carcinoma: Natural history, current management, and emerging tools. Biologics. 6:207–219. 2012.PubMed/NCBI

2 

Marquardt JU and Thorgeirsson SS: SnapShot: Hepatocelluar carcinoma. Cancer Cell. 25:550.e12014. View Article : Google Scholar : PubMed/NCBI

3 

Takai A, Dang HT and Wang XW: Identification of drivers from cancer genome diversity in hepatocellular carcinoma. Int J Mol Sci. 15:11142–11160. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Pinyol R, Nault JC, Quetglas IM, Zucman-Rossi J and Llovet JM: Molecular profiling of liver tumors: Classification and clinical translation for decision making. Semin Liver Dis. 34:363–375. 2014. View Article : Google Scholar : PubMed/NCBI

5 

Moinzadeh P, Breuhahn K, Stützer H and Schirmacher P: Chromosome alterations in human hepatocellular carcinomas correlate with aetiology and histological grade - results of an explorative CGH meta-analysis. Br J Cancer. 92:935–941. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Chochi Y, Kawauchi S, Nakao M, Furuya T, Hashimoto K, Oga A, Oka M and Sasaki K: A copy number gain of the 6p arm is linked with advanced hepatocellular carcinoma: An array-based comparative genomic hybridization study. J Pathol. 217:677–684. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Katoh H, Ojima H, Kokubu A, Saito S, Kondo T, Kosuge T, Hosoda F, Imoto I, Inazawa J, Hirohashi S and Shibata T: Genetically distinct and clinically relevant classification of hepatocellular carcinoma: Putative therapeutic targets. Gastroenterology. 133:1475–1486. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Yuan BZ, Miller MJ, Keck CL, Zimonjic DB, Thorgeirsson SS and Popescu NC: Cloning, characterization, and chromosomal localization of a gene frequently deleted in human liver cancer (DLC-1) homologous to rat RhoGAP. Cancer Res. 58:2196–2199. 1998.PubMed/NCBI

9 

Neel BG, Jhanwar SC, Chaganti RS and Hayward WS: Two human c-onc genes are located on the long arm of chromosome 8. Proc Natl Acad Sci USA. 79:7842–7846. 1982. View Article : Google Scholar : PubMed/NCBI

10 

Durkin ME, Yuan BZ, Zhou X, Zimonjic DB, Lowy DR, Thorgeirsson SS and Popescu NC: DLC-1: A Rho GTPase-activating protein and tumour suppressor. J Cell Mol Med. 11:1185–1207. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Lukasik D, Wilczek E, Wasiutynski A and Gornicka B: Deleted in liver cancer protein family in human malignancies (Review). Oncol Lett. 2:763–768. 2011.PubMed/NCBI

12 

Dang CV: MYC on the path to cancer. Cell. 149:22–35. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Roessler S, Long EL, Budhu A, Chen Y, Zhao X, Ji J, Walker R, Jia HL, Ye QH, Qin LX, et al: Integrative genomic identification of genes on 8p associated with hepatocellular carcinoma progression and patient survival. Gastroenterology. 142:957–966. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Hoshida Y, Nijman SM, Kobayashi M, Chan JA, Brunet JP, Chiang DY, Villanueva A, Newell P, Ikeda K, Hashimoto M, et al: Integrative transcriptome analysis reveals common molecular subclasses of human hepatocellular carcinoma. Cancer Res. 69:7385–7392. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Kaposi-Novak P, Libbrecht L, Woo HG, Lee YH, Sears NC, Coulouarn C, Conner EA, Factor VM, Roskams T and Thorgeirsson SS: Central role of c-Myc during malignant conversion in human hepatocarcinogenesis. Cancer Res. 69:2775–2782. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Xue W, Krasnitz A, Lucito R, Sordella R, Vanaelst L, Cordon-Cardo C, Singer S, Kuehnel F, Wigler M, Powers S, et al: DLC1 is a chromosome 8p tumor suppressor whose loss promotes hepatocellular carcinoma. Genes Dev. 22:1439–1444. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Beer S, Zetterberg A, Ihrie RA, McTaggart RA, Yang Q, Bradon N, Arvanitis C, Attardi LD, Feng S, Ruebner B, et al: Developmental context determines latency of MYC-induced tumorigenesis. PLoS Biol. 2:e3322004. View Article : Google Scholar : PubMed/NCBI

18 

Zimonjic DB and Popescu NC: Role of DLC1 tumor suppressor gene and MYC oncogene in pathogenesis of human hepatocellular carcinoma: Potential prospects for combined targeted therapeutics (review). Int J Oncol. 41:393–406. 2012.PubMed/NCBI

19 

Guan M, Tripathi V, Zhou X and Popescu NC: Adenovirus-mediated restoration of expression of the tumor suppressor gene DLC1 inhibits the proliferation and tumorigenicity of aggressive, androgen-independent human prostate cancer cell lines: Prospects for gene therapy. Cancer Gene Ther. 15:371–381. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Yuan BZ, Zhou X, Durkin ME, Zimonjic DB, Gumundsdottir K, Eyfjord JE, Thorgeirsson SS and Popescu NC: DLC-1 gene inhibits human breast cancer cell growth and in vivo tumorigenicity. Oncogene. 22:445–450. 2003. View Article : Google Scholar : PubMed/NCBI

21 

Yang X, Popescu NC and Zimonjic DB: DLC1 interaction with S100A10 mediates inhibition of in vitro cell invasion and tumorigenicity of lung cancer cells through a RhoGAP-independent mechanism. Cancer Res. 71:2916–2925. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Chan CH, Lee SW, Li CF, Wang J, Yang WL, Wu CY, Wu J, Nakayama KI, Kang HY, Huang HY, et al: Deciphering the transcriptional complex critical for RhoA gene expression and cancer metastasis. Nat Cell Biol. 12:457–467. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Wang Y, Du H and Zhai G: Recent advances in active hepatic targeting drug delivery system. Curr Drug Targets. 15:573–599. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Treichel U, Meyer Zum Büschenfelde KH, Stockert RJ, Poralla T and Gerken G: The asialoglycoprotein receptor mediates hepatic binding and uptake of natural hepatitis B virus particles derived from viraemic carriers. J Gen Virol. 75:3021–3029. 1994. View Article : Google Scholar : PubMed/NCBI

25 

Reig M, Darnell A, Forner A, Rimola J, Ayuso C and Bruix J: Systemic therapy for hepatocellular carcinoma: The issue of treatment stage migration and registration of progression using the BCLC-refined RECIST. Semin Liver Dis. 34:444–455. 2014. View Article : Google Scholar : PubMed/NCBI

26 

Mikhail S, Cosgrove D and Zeidan A: Hepatocellular carcinoma: Systemic therapies and future perspectives. Expert Rev Anticancer Ther. 14:1205–1218. 2014. View Article : Google Scholar : PubMed/NCBI

27 

Albihn A, Johnsen JI and Henriksson MA: MYC in oncogenesis and as a target for cancer therapies. Adv Cancer Res. 107:163–224. 2010. View Article : Google Scholar : PubMed/NCBI

28 

McKeown MR and Bradner JE: Therapeutic strategies to inhibit MYC. Cold Spring Harb Perspect Med. 4:a0142662014. View Article : Google Scholar : PubMed/NCBI

29 

Jaffe AB and Hall A: Rho GTPases: Biochemistry and biology. Annu Rev Cell Dev Biol. 21:247–269. 2005. View Article : Google Scholar : PubMed/NCBI

30 

Grise F, Bidaud A and Moreau V: Rho GTPases in hepatocellular carcinoma. Biochim Biophys Acta. 1795:137–151. 2009.PubMed/NCBI

31 

Wong CM, Lee JM, Ching YP, Jin DY and Ng IO: Genetic and epigenetic alterations of DLC-1 gene in hepatocellular carcinoma. Cancer Res. 63:7646–7651. 2003.PubMed/NCBI

32 

Healy KD, Hodgson L, Kim TY, Shutes A, Maddileti S, Juliano RL, Hahn KM, Harden TK, Bang YJ and Der CJ: DLC-1 suppresses non-small cell lung cancer growth and invasion by RhoGAP-dependent and independent mechanisms. Mol Carcinog. 47:326–337. 2008. View Article : Google Scholar : PubMed/NCBI

33 

Wong CM, Yam JW, Ching YP, Yau TO, Leung TH, Jin DY and Ng IO: Rho GTPase-activating protein deleted in liver cancer suppresses cell proliferation and invasion in hepatocellular carcinoma. Cancer Res. 65:8861–8868. 2005. View Article : Google Scholar : PubMed/NCBI

34 

Qian X, Li G, Asmussen HK, Asnaghi L, Vass WC, Braverman R, Yamada KM, Popescu NC, Papageorge AG and Lowy DR: Oncogenic inhibition by a deleted in liver cancer gene requires cooperation between tensin binding and Rho-specific GTPase-activating protein activities. Proc Natl Acad Sci USA. 104:9012–9017. 2007. View Article : Google Scholar : PubMed/NCBI

35 

Berenjeno IM, Núñez F and Bustelo XR: Transcriptomal profiling of the cellular transformation induced by Rho subfamily GTPases. Oncogene. 26:4295–4305. 2007. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yang X, Zhou X, Tone P, Durkin ME and Popescu NC: Cooperative antiproliferative effect of coordinated ectopic expression of DLC1 tumor suppressor protein and silencing of MYC oncogene expression in liver cancer cells: Therapeutic implications. Oncol Lett 12: 1591-1596, 2016.
APA
Yang, X., Zhou, X., Tone, P., Durkin, M.E., & Popescu, N.C. (2016). Cooperative antiproliferative effect of coordinated ectopic expression of DLC1 tumor suppressor protein and silencing of MYC oncogene expression in liver cancer cells: Therapeutic implications. Oncology Letters, 12, 1591-1596. https://doi.org/10.3892/ol.2016.4781
MLA
Yang, X., Zhou, X., Tone, P., Durkin, M. E., Popescu, N. C."Cooperative antiproliferative effect of coordinated ectopic expression of DLC1 tumor suppressor protein and silencing of MYC oncogene expression in liver cancer cells: Therapeutic implications". Oncology Letters 12.2 (2016): 1591-1596.
Chicago
Yang, X., Zhou, X., Tone, P., Durkin, M. E., Popescu, N. C."Cooperative antiproliferative effect of coordinated ectopic expression of DLC1 tumor suppressor protein and silencing of MYC oncogene expression in liver cancer cells: Therapeutic implications". Oncology Letters 12, no. 2 (2016): 1591-1596. https://doi.org/10.3892/ol.2016.4781
Copy and paste a formatted citation
x
Spandidos Publications style
Yang X, Zhou X, Tone P, Durkin ME and Popescu NC: Cooperative antiproliferative effect of coordinated ectopic expression of DLC1 tumor suppressor protein and silencing of MYC oncogene expression in liver cancer cells: Therapeutic implications. Oncol Lett 12: 1591-1596, 2016.
APA
Yang, X., Zhou, X., Tone, P., Durkin, M.E., & Popescu, N.C. (2016). Cooperative antiproliferative effect of coordinated ectopic expression of DLC1 tumor suppressor protein and silencing of MYC oncogene expression in liver cancer cells: Therapeutic implications. Oncology Letters, 12, 1591-1596. https://doi.org/10.3892/ol.2016.4781
MLA
Yang, X., Zhou, X., Tone, P., Durkin, M. E., Popescu, N. C."Cooperative antiproliferative effect of coordinated ectopic expression of DLC1 tumor suppressor protein and silencing of MYC oncogene expression in liver cancer cells: Therapeutic implications". Oncology Letters 12.2 (2016): 1591-1596.
Chicago
Yang, X., Zhou, X., Tone, P., Durkin, M. E., Popescu, N. C."Cooperative antiproliferative effect of coordinated ectopic expression of DLC1 tumor suppressor protein and silencing of MYC oncogene expression in liver cancer cells: Therapeutic implications". Oncology Letters 12, no. 2 (2016): 1591-1596. https://doi.org/10.3892/ol.2016.4781
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