Skip to main content
Log in

RETRACTED ARTICLE: MiRNA-494 inhibits metastasis of cervical cancer through Pttg1

  • Research Article
  • Published:
Tumor Biology

This article was retracted on 20 April 2017

Abstract

Many cervical cancer (CC) patients experience early cancer metastasis, resulting in poor therapeutic outcome after resection of primary cancer. Hence, there is a compelling requirement for understanding of the molecular mechanisms underlying the invasiveness control of CC. Pituitary tumor-transforming gene 1 (Pttg1) has been recently reported to promote cancer cell growth and metastasis in a number of various tumors. However, its regulation by microRNAs (miRNAs) as well as its role in CC have not been clarified. Here, we reported significantly higher levels of Pttg1 and significantly lower levels of miR-494 in the resected CC tissue, compared with the adjacent normal cervical tissue from the same patient. Interestingly, Pttg1 levels inversely correlated with miR-494 levels. In vitro, Pttg1 levels determined CC cell invasiveness and were inhibited by miR-494 levels. However, miR-494 levels were not affected by Pttg1 levels. Furthermore, miR-494 inhibited Pttg1 expression in CC cells, through directly binding and inhibition on 3′-UTR of Pttg1 mRNA. Together, our data suggest that Pttg1 may increase CC cell metastasis, which is negatively regulated by miR-494. Our work thus highlights a novel molecular regulatory machinery in metastasis of CC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Kanayama T, Mabuchi S, Fujita M, Kimura T. Calcaneal metastasis in uterine cervical cancer: a case report and a review of the literature. Eur J Gynaecol Oncol. 2012;33:524–5.

    CAS  PubMed  Google Scholar 

  2. Setoodeh R, Hakam A, Shan Y. Cerebral metastasis of cervical cancer, report of two cases and review of the literature. Int J Clin Exp Pathol. 2012;5:710–4.

    PubMed  PubMed Central  Google Scholar 

  3. Peters P, Bandi H, Efendy J, Perez-Smith A, Olson S. Rapid growth of cervical cancer metastasis in the brain. J Clin Neurosci. 2010;17:1211–2.

    Article  CAS  PubMed  Google Scholar 

  4. Chen B, Zhang C, Dong P, Guo Y, Mu N. Molecular regulation of cervical cancer growth and invasion by VEGFA. Tumour Biol. 2014;35:11587–93.

    Article  CAS  PubMed  Google Scholar 

  5. Yu R, Ren SG, Horwitz GA, Wang Z, Melmed S. Pituitary tumor transforming gene (pttg) regulates placental JEG-3 cell division and survival: evidence from live cell imaging. Mol Endocrinol. 2000;14:1137–46.

    Article  CAS  PubMed  Google Scholar 

  6. Caporali S, Alvino E, Levati L, Esposito AI, Ciomei M, Brasca MG, et al. Down-regulation of the pttg1 proto-oncogene contributes to the melanoma suppressive effects of the cyclin-dependent kinase inhibitor PHA-848125. Biochem Pharmacol. 2012;84:598–611.

    Article  CAS  PubMed  Google Scholar 

  7. Vlotides G, Eigler T, Melmed S. Pituitary tumor-transforming gene: physiology and implications for tumorigenesis. Endocr Rev. 2007;28:165–86.

    Article  CAS  PubMed  Google Scholar 

  8. Tfelt-Hansen J, Kanuparthi D, Chattopadhyay N. The emerging role of pituitary tumor transforming gene in tumorigenesis. Clin Med Res. 2006;4:130–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Panguluri SK, Yeakel C, Kakar SS. Pttg: an important target gene for ovarian cancer therapy. J Ovarian Res. 2008;1:6.

    Article  PubMed  PubMed Central  Google Scholar 

  10. El-Naggar SM, Malik MT, Kakar SS. Small interfering RNA against Pttg: a novel therapy for ovarian cancer. Int J Oncol. 2007;31:137–43.

    CAS  PubMed  Google Scholar 

  11. Chen G, Li J, Li F, Li X, Zhou J, Lu Y, et al. Inhibitory effects of anti-sense Pttg on malignant phenotype of human ovarian carcinoma cell line SK-OV-3. J Huazhong Univ Sci Technol Med Sci = Hua zhong ke ji da xue xue bao Yi xue Ying De wen ban = Huazhong keji daxue xuebao Yixue Yingdewen ban. 2004;24:369–72.

    Article  PubMed  Google Scholar 

  12. Yan S, Zhou C, Lou X, Xiao Z, Zhu H, Wang Q, et al. Pttg overexpression promotes lymph node metastasis in human esophageal squamous cell carcinoma. Cancer Res. 2009;69:3283–90.

    Article  CAS  PubMed  Google Scholar 

  13. Zhou C, Liu S, Zhou X, Xue L, Quan L, Lu N, et al. Overexpression of human pituitary tumor transforming gene (hpttg), is regulated by beta-catenin/TCF pathway in human esophageal squamous cell carcinoma. Int J Cancer. 2005;113:891–8.

    Article  CAS  PubMed  Google Scholar 

  14. Shibata Y, Haruki N, Kuwabara Y, Nishiwaki T, Kato J, Shinoda N, et al. Expression of Pttg (pituitary tumor transforming gene) in esophageal cancer. Jpn J Clin Oncol. 2002;32:233–7.

    Article  PubMed  Google Scholar 

  15. Zhang ML, Lu S, Zheng SS. Epigenetic changes of pituitary tumor-derived transforming gene 1 in pancreatic cancer. Hepatobil Pancreat Dis Int. 2008;7:313–7.

    CAS  Google Scholar 

  16. Ai J, Zhang Z, Xin D, Zhu H, Yan Q, Xin Z, et al. Identification of over-expressed genes in human renal cell carcinoma by combining suppression subtractive hybridization and cDNA library array. Sci China C Life Sci. 2004;47:148–57.

    Article  PubMed  Google Scholar 

  17. Dominguez A, Ramos-Morales F, Romero F, Rios RM, Dreyfus F, Tortolero M, et al. Hpttg, a human homologue of rat Pttg, is overexpressed in hematopoietic neoplasms. Evidence for a transcriptional activation function of hpttg. Oncogene. 1998;17:2187–93.

    Article  CAS  PubMed  Google Scholar 

  18. Zhou C, Tong Y, Wawrowsky K, Melmed S. Pttg acts as a stat3 target gene for colorectal cancer cell growth and motility. Oncogene. 2014;33:851–61.

    Article  CAS  PubMed  Google Scholar 

  19. Kim DS, Franklyn JA, Smith VE, Stratford AL, Pemberton HN, Warfield A, et al. Securin induces genetic instability in colorectal cancer by inhibiting double-stranded DNA repair activity. Carcinogenesis. 2007;28:749–59.

    Article  CAS  PubMed  Google Scholar 

  20. Huang SQ, Liao QJ, Wang XW, Xin DQ, Chen SX, Wu QJ, et al. RNAi-mediated knockdown of pituitary tumor-transforming gene-1 (Pttg1) suppresses the proliferation and invasive potential of PC3 human prostate cancer cells. Braz J Med Biol Res. 2012;45:995–1001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Huang S, Liao Q, Li L, Xin D. Pttg1 inhibits smad3 in prostate cancer cells to promote their proliferation. Tumour Biol. 2014;35:6265–70.

    Article  CAS  PubMed  Google Scholar 

  22. Castilla C, Flores ML, Medina R, Perez-Valderrama B, Romero F, Tortolero M, et al. Prostate cancer cell response to paclitaxel is affected by abnormally expressed securin Pttg1. Mol Cancer Ther. 2014;13:2372–83.

    Article  CAS  PubMed  Google Scholar 

  23. Cao XL, Gao JP, Wang W, Xu Y, Shi HY, Zhang X. Expression of pituitary tumor transforming gene 1 is an independent factor of poor prognosis in localized or locally advanced prostate cancer cases receiving hormone therapy. Asian Pac J Cancer Prev. 2012;13:3083–8.

    Article  PubMed  Google Scholar 

  24. Castilla C, Flores ML, Conde JM, Medina R, Torrubia FJ, Japon MA, et al. Downregulation of protein tyrosine phosphatase ptpl1 alters cell cycle and upregulates invasion-related genes in prostate cancer cells. Clin Exp Metastasis. 2012;29:349–58.

    Article  CAS  PubMed  Google Scholar 

  25. Singh SV, Powolny AA, Stan SD, Xiao D, Arlotti JA, Warin R, et al. Garlic constituent diallyl trisulfide prevents development of poorly differentiated prostate cancer and pulmonary metastasis multiplicity in tramp mice. Cancer Res. 2008;68:9503–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Bacac M, Provero P, Mayran N, Stehle JC, Fusco C, Stamenkovic I. A mouse stromal response to tumor invasion predicts prostate and breast cancer patient survival. PLoS One. 2006;1:e32.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Crosby ME, Jacobberger J, Gupta D, Macklis RM, Almasan A. E2f4 regulates a stable G2 arrest response to genotoxic stress in prostate carcinoma. Oncogene. 2007;26:1897–909.

    Article  CAS  PubMed  Google Scholar 

  28. Zhu X, Mao Z, Na Y, Guo Y, Wang X, Xin D. Significance of pituitary tumor transforming gene 1 (Pttg1) in prostate cancer. Anticancer Res. 2006;26:1253–9.

    CAS  PubMed  Google Scholar 

  29. Di Leva G, Croce CM. MiRNA profiling of cancer. Curr Opin Genet Dev. 2013;23:3–11.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Pereira DM, Rodrigues PM, Borralho PM, Rodrigues CM. Delivering the promise of miRNA cancer therapeutics. Drug Discov Today. 2013;18:282–9.

    Article  CAS  PubMed  Google Scholar 

  31. He W, Li Y, Chen X, Lu L, Tang B, Wang Z, et al. Mir-494 acts as an anti-oncogene in gastric carcinoma by targeting c-myc. J Gastroenterol Hepatol. 2014;29:1427–34.

    Article  CAS  PubMed  Google Scholar 

  32. Zhou RP, Chen G, Shen ZL, Pan LQ. Cinobufacin suppresses cell proliferation via mir-494 in BGC-823 gastric cancer cells. Asian Pac J Cancer Prev. 2014;15:1241–5.

    Article  PubMed  Google Scholar 

  33. Bai Y, Sun Y, Peng J, Liao H, Gao H, Guo Y, et al. Overexpression of secretagogin inhibits cell apoptosis and induces chemoresistance in small cell lung cancer under the regulation of mir-494. Oncotarget. 2014;5:7760–75.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Romano G, Acunzo M, Garofalo M, Di Leva G, Cascione L, Zanca C, et al. Mir-494 is regulated by ERK1/2 and modulates trail-induced apoptosis in non-small-cell lung cancer through bim down-regulation. Proc Natl Acad Sci U S A. 2012;109:16570–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Liborio-Kimura TN, Jung HM, Chan EK. Mir-494 represses hoxa10 expression and inhibits cell proliferation in oral cancer. Oral Oncol. 2015;51:151–7.

    Article  CAS  PubMed  Google Scholar 

  36. Ries J, Vairaktaris E, Agaimy A, Kintopp R, Baran C, Neukam FW, et al. Mir-186, mir-3651 and mir-494: potential biomarkers for oral squamous cell carcinoma extracted from whole blood. Oncol Rep. 2014;31:1429–36.

    CAS  PubMed  Google Scholar 

  37. Kwak SY, Yang JS, Kim BY, Bae IH, Han YH. Ionizing radiation-inducible mir-494 promotes glioma cell invasion through EGFR stabilization by targeting p190b RhoGap. Biochim Biophys Acta. 1843;2014:508–16.

    Google Scholar 

  38. Asuthkar S, Velpula KK, Nalla AK, Gogineni VR, Gondi CS, Rao JS. Irradiation-induced angiogenesis is associated with an mmp-9-mir-494-syndecan-1 regulatory loop in medulloblastoma cells. Oncogene. 2014;33:1922–33.

    Article  CAS  PubMed  Google Scholar 

  39. Puck TT, Marcus PI, Cieciura SJ. Clonal growth of mammalian cells in vitro; growth characteristics of colonies from single Hela cells with and without a feeder layer. J Exp Med. 1956;103:273–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Liang CC, Park AY, Guan JL. In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc. 2007;2:329–33.

    Article  CAS  PubMed  Google Scholar 

  41. Solbach C, Roller M, Peters S, Nicoletti M, Kaufmann M, Knecht R. Pituitary tumor-transforming gene (Pttg): a novel target for anti-tumor therapy. Anticancer Res. 2005;25:121–5.

    CAS  PubMed  Google Scholar 

  42. Yamanaka S, Campbell NR, An F, Kuo SC, Potter JJ, Mezey E, et al. Coordinated effects of microRNA-494 induce G(2)/M arrest in human cholangiocarcinoma. Cell Cycle. 2012;11:2729–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Conflicts of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ying Tong.

Additional information

The Publisher and Editor retract this article in accordance with the recommendations of the Committee on Publication Ethics (COPE). After a thorough investigation we have strong reason to believe that the peer review process was compromised.

An erratum to this article is available at http://dx.doi.org/10.1007/s13277-017-5487-6.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, B., Hou, Z., Li, C. et al. RETRACTED ARTICLE: MiRNA-494 inhibits metastasis of cervical cancer through Pttg1. Tumor Biol. 36, 7143–7149 (2015). https://doi.org/10.1007/s13277-015-3440-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-015-3440-0

Keywords

Navigation