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Article

RASSF1A promotes apoptosis and suppresses the proliferation of ovarian cancer cells

  • Authors:
    • Lingjie Fu
    • Shulan Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Gynaecology and Obstetrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
  • Pages: 1153-1160
    |
    Published online on: February 25, 2014
       https://doi.org/10.3892/ijmm.2014.1671
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Abstract

As the most lethal gynecological malignancy, ovarian cancer has attracted much attention over the past few decades; however, the early detection of this malignancy has been largely unsuccessful. The aim of this study was to determine the effects of Ras-association domain family 1, isoform A (RASSF1A) on ovarian cancer and to elucidate the molecular mechanisms responsible for these effects. The expression of RASSF1A in different ovarian cancer cells was detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The morphology, structure, apoptosis and proliferation of differently treated SKOV-3 cells were then analyzed using a fluorescence microscope, transmission electron microscope, flow cytometer and by western blot analysis, respectively. Moreover, the GSE14407 affymetrix microarray data were downloaded from the Gene Expression Omnibus database and the expression of RASSF1A was quantified by Spotfire DecisionSite software. A RASSF1A related protein-protein interaction (PPI) network was then constructed using STRING and Cytoscape software. Finally, DAVID was utilized to perform KEGG pathway enrichment analysis of the network. RASSF1A was expressed in the HO8910, HO8910PM cells and the SKOV-3 cells transfected with RASSF1A, whereas it was absent in the other SKOV-3 cells and OVCAR-3 cells. Additionally, compared with the other SKOV-3 cells, the nucleus of SKOV-3 cells transfected with RASSF1A was vacuolated, apoptosis was increased, and the expression of cyclin D1 and survivin was decreased (P<0.05), and that of p27 and caspase-3 was increased (P<0.01). Additionally, 10 genes, including serine/threonine kinase (STK)3, STK4, Harvey rat sarcoma viral oncogene homolog (HRAS) and cell division cycle 20 (CDC20), were found to have close interactions with RASSF1A in the PPI network. Finally, a total of 8 enriched pathways, such as bladder cancer, non-small cell lung cancer and pathways in cancer were identified. To our knowledge, this is the first study to explore the biological functions and the underlying mechanisms of action of RASSF1A in the development of ovarian cancer. Our findings may provide a novel therapeutic target for ovarian cancer.
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1 

Yap TA, Carden CP and Kaye SB: Beyond chemotherapy: targeted therapies in ovarian cancer. Nat Rev Cancer. 9:167–181. 2009. View Article : Google Scholar : PubMed/NCBI

2 

Buys SS, Partridge E, Black A, et al: Effect of screening on ovarian cancer mortality: the prostate, lung, colorectal and ovarian (PLCO) cancer screening randomized controlled trial. JAMA. 305:2295–2303. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Vaughan S, Coward JI, Bast RCJC, et al: Rethinking ovarian cancer: recommendations for improving outcomes. Nat Rev Cancer. 11:719–725. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Moore RG, Miller MC, Eklund EE, Lu KH, Bast RC Jr and Lambert-Messerlian G: Serum levels of the ovarian cancer biomarker HE4 are decreased in pregnancy and increase with age. Am J Obstet Gynecol. 206:349.e341–e347. 2012.PubMed/NCBI

5 

Nosov V, Su F, Amneus M, et al: Validation of serum biomarkers for detection of early-stage ovarian cancer. Am J Obstet Gynecol. 200:639.e631–e635. 2009.PubMed/NCBI

6 

Weiland F, Martin K, Oehler MK and Hoffmann P: Deciphering the molecular nature of ovarian cancer biomarker CA125. Int J Mol Sci. 13:10568–10582. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Yee KS, Grochola L, Hamilton G, et al: A RASSF1A polymorphism restricts p53/p73 activation and associates with poor survival and accelerated age of onset of soft tissue sarcoma. Cancer Res. 72:2206–2217. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Donninger H, Barnoud T, Nelson N, et al: RASSF1A and the rs2073498 cancer associated SNP. Front oncol. 1:542011. View Article : Google Scholar : PubMed/NCBI

9 

Kassler S, Donninger H, Birrer MJ and Clark GJ: RASSF1A and the taxol response in ovarian cancer. Mol Biol Int. 2012:2632672012. View Article : Google Scholar : PubMed/NCBI

10 

Liu L, Kron KJ, Pethe VV, et al: Association of tissue promoter methylation levels of APC, TGFβ2, HOXD3 and RASSF1A with prostate cancer progression. Int J Cancer. 129:2454–2462. 2011.PubMed/NCBI

11 

Brait M, Loyo M, Rosenbaum E, et al: Correlation between BRAF mutation and promoter methylation of TIMP3, RARβ2 and RASSF1A in thyroid cancer. Epigenetics. 7:710–719. 2012.PubMed/NCBI

12 

Kloten V, Becker B, Winner K, et al: Promoter hypermethylation of the tumor-suppressor genes ITIH5, DKK3, and RASSF1A as novel biomarkers for blood-based breast cancer screening. Breast Cancer Res. 15:R42013. View Article : Google Scholar : PubMed/NCBI

13 

Senchenko VN, Anedchenko EA, Kondratieva TT, et al: Simultaneous down-regulation of tumor suppressor genes RBSP3/CTDSPL, NPRL2/G21 and RASSF1A in primary non-small cell lung cancer. BMC cancer. 10:752010. View Article : Google Scholar : PubMed/NCBI

14 

Yi M, Yang J, Chen X, et al: RASSF1A suppresses melanoma development by modulating apoptosis and cell-cycle progression. J Cell Physiol. 226:2360–2369. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Amin KS and Banerjee PP: The cellular functions of RASSF1A and its inactivation in prostate cancer. J Carcinog. 11:32012. View Article : Google Scholar : PubMed/NCBI

16 

Laird PW: Principles and challenges of genomewide DNA methylation analysis. Nat Rev Genet. 11:191–203. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Oh JH, Craft JM, Townsend R, Deasy JO, Bradley JD and El Naqa I: A bioinformatics approach for biomarker identification in radiation-induced lung inflammation from limited proteomics data. J Proteome Res. 10:1406–1415. 2011. View Article : Google Scholar : PubMed/NCBI

18 

Goertsches RH, Zettl UK and Hecker M: Sieving treatment biomarkers from blood gene-expression profiles: a pharmacogenomic update on two types of multiple sclerosis therapy. Pharmacogenomics. 12:423–432. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Kruger NJ: The Bradford method for protein quantitation. The Protein Protocols Handbook. Springer; New York, NY: pp. 17–24. 2009, View Article : Google Scholar

20 

Chang C, Zhang C, Zhao X, Kuang X, Tang H and Xiao X: Differential regulation of mitogen-activated protein kinase signaling pathways in human with different types of mitral valvular disease. J Surg Res. 181:49–59. 2013. View Article : Google Scholar

21 

Bowen NJ, Walker LD, Matyunina LV, et al: Gene expression profiling supports the hypothesis that human ovarian surface epithelia are multipotent and capable of serving as ovarian cancer initiating cells. BMC Med Genomics. 2:712009. View Article : Google Scholar

22 

Russell LJ, Capasso M, Vater I, et al: Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia. Blood. 114:2688–2698. 2009. View Article : Google Scholar : PubMed/NCBI

23 

Szklarczyk D, Franceschini A, Kuhn M, et al: The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res. 39:D561–D568. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Shannon P, Markiel A, Ozier O, et al: Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13:2498–2504. 2003. View Article : Google Scholar : PubMed/NCBI

25 

Huang da W, Sherman BT and Lempicki RA: Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 4:44–57. 2009.PubMed/NCBI

26 

Kanehisa M, Goto S, Furumichi M, Tanabe M and Hirakawa M: KEGG for representation and analysis of molecular networks involving diseases and drugs. Nucleic Acids Res. 38:D355–D360. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Kipps E, Tan DS and Kaye SB: Meeting the challenge of ascites in ovarian cancer: new avenues for therapy and research. Nat Rev Cancer. 13:273–282. 2013. View Article : Google Scholar : PubMed/NCBI

28 

Patankar NA, Pritchard J, Van Grinsven M, Osooly M and Bally MB: Topotecan and doxorubicin combination to treat recurrent ovarian cancer: the influence of drug exposure time and delivery systems to achieve optimum therapeutic activity. Clin Cancer Res. 19:865–877. 2013. View Article : Google Scholar

29 

Pan Y, Du Zhen-Wu D, Zhou JW, et al: MicroRNA-mediated silencing of RhoC inhibits tumor invasion and increases chemosensitivity to paclitaxel in SKOV3 cells in vitro. Chem Res Chin Univ. 27:70–74. 2011.

30 

Hergovich A and Hemmings BA: Hippo signalling in the G2/M cell cycle phase: lessons learned from the yeast MEN and SIN pathways. Semin Cell Dev Biol. 23:794–802. 2012. View Article : Google Scholar : PubMed/NCBI

31 

Matallanas D, Romano D, Yee K, et al: RASSF1A elicits apoptosis through an MST2 pathway directing proapoptotic transcription by the p73 tumor suppressor protein. Mol Cell. 27:962–975. 2007. View Article : Google Scholar : PubMed/NCBI

32 

Jirawatnotai S, Hu Y, Michowski W, et al: A function for cyclin D1 in DNA repair uncovered by protein interactome analyses in human cancers. Nature. 474:230–234. 2011. View Article : Google Scholar : PubMed/NCBI

33 

Cheung CH, Cheng L, Chang KY, Chen HH and Chang JY: Investigations of survivin: the past, present and future. Front Biosci (Landmark Ed). 16:952–961. 2010. View Article : Google Scholar : PubMed/NCBI

34 

Chu IM, Hengst L and Slingerland JM: The Cdk inhibitor p27 in human cancer: prognostic potential and relevance to anticancer therapy. Nat Rev Cancer. 8:253–267. 2008. View Article : Google Scholar : PubMed/NCBI

35 

Larsen BD, Rampalli S, Burns LE, Brunette S, Dilworth FJ and Megeney LA: Caspase 3/caspase-activated DNase promote cell differentiation by inducing DNA strand breaks. Proc Natl Acad Sci USA. 107:4230–4235. 2010. View Article : Google Scholar : PubMed/NCBI

36 

Bennani-Baiti IM: Epigenetic and epigenomic mechanisms shape sarcoma and other mesenchymal tumor pathogenesis. Epigenomics. 3:715–732. 2011. View Article : Google Scholar : PubMed/NCBI

37 

Sun XF, Li L, Li XJ and Shen W: Methylation pattern of oncogene HRAS gene promoter region and its clinical relevance to urocystic tumorigenesis. Mol Biol Rep. 39:8431–8437. 2012. View Article : Google Scholar : PubMed/NCBI

38 

Liu L, Baier K, Dammann RH and Pfeifer GP: The tumor suppressor RASSF1A does not interact with Cdc20, an activator of the anaphase-promoting complex. Cell Cycle. 6:1663–1665. 2007. View Article : Google Scholar : PubMed/NCBI

39 

Kim JS, Chae Y, Ha YS, et al: Ras association domain family 1A: a promising prognostic marker in recurrent nonmuscle invasive bladder cancer. Clin Genitourin Cancer. 10:114–120. 2012. View Article : Google Scholar : PubMed/NCBI

40 

Del Re DP and Sadoshima J: RASSF1A Signaling in the heart: novel functions beyond tumor suppression. Mol Biol Int. 2012:1542832012.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Fu L and Zhang S: RASSF1A promotes apoptosis and suppresses the proliferation of ovarian cancer cells. Int J Mol Med 33: 1153-1160, 2014.
APA
Fu, L., & Zhang, S. (2014). RASSF1A promotes apoptosis and suppresses the proliferation of ovarian cancer cells. International Journal of Molecular Medicine, 33, 1153-1160. https://doi.org/10.3892/ijmm.2014.1671
MLA
Fu, L., Zhang, S."RASSF1A promotes apoptosis and suppresses the proliferation of ovarian cancer cells". International Journal of Molecular Medicine 33.5 (2014): 1153-1160.
Chicago
Fu, L., Zhang, S."RASSF1A promotes apoptosis and suppresses the proliferation of ovarian cancer cells". International Journal of Molecular Medicine 33, no. 5 (2014): 1153-1160. https://doi.org/10.3892/ijmm.2014.1671
Copy and paste a formatted citation
x
Spandidos Publications style
Fu L and Zhang S: RASSF1A promotes apoptosis and suppresses the proliferation of ovarian cancer cells. Int J Mol Med 33: 1153-1160, 2014.
APA
Fu, L., & Zhang, S. (2014). RASSF1A promotes apoptosis and suppresses the proliferation of ovarian cancer cells. International Journal of Molecular Medicine, 33, 1153-1160. https://doi.org/10.3892/ijmm.2014.1671
MLA
Fu, L., Zhang, S."RASSF1A promotes apoptosis and suppresses the proliferation of ovarian cancer cells". International Journal of Molecular Medicine 33.5 (2014): 1153-1160.
Chicago
Fu, L., Zhang, S."RASSF1A promotes apoptosis and suppresses the proliferation of ovarian cancer cells". International Journal of Molecular Medicine 33, no. 5 (2014): 1153-1160. https://doi.org/10.3892/ijmm.2014.1671
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