Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Role and the molecular mechanism of lncRNA PTENP1 in regulating the proliferation and invasion of cervical cancer cells

Abstract

Cervical cancer ranks second in the major causes of cancer-relevant death in female population worldwide. It is extensively reported that lncRNAs are implicated in biological activities of diverse cancers. LncRNA PTENP1 has been recently reported as a tumor suppressor in several malignancies. However, the pathophysiological function and the potential regulatory mechanism of PTENP1 in cervical cancer have never been studied. In this research, PTENP1 was pronouncedly downregulated in cervical cancer tissues, and low PTENP1 level was tightly linked to advanced stage and poor prognosis in cervical cancer. Overexpressing PTENP1 inhibited cervical cancer progression by suppressing cell growth, motility and epithelial-to-mesenchymal transition (EMT). PTENP1 was confirmed to decoy miR-27a-3p to upregulate EGR1 expression in cervical cancer cells. Additionally, EGR1 knockdown reversed the repressive effect of PTENP1 overexpression on cervical cancer progression. In a word, current study was the first to uncover the biological functions of PTENP1 as well as its modulatory mechanism in cervical cancer, which may offer a new potent target for treating patients with cervical cancer.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: PTENP1 is predominantly downregulated in cervical cancer.
Fig. 2: PTENP1 overexpression inhibits cell proliferation and facilitates cell apoptosis in cervical cancer.
Fig. 3: PTENP1 overexpression represses cell migration and invasion and EMT in cervical cancer.
Fig. 4: PTENP1 sponges miR-27a-3p in cervical cancer.
Fig. 5: PTENP1 sponges miR-27a-3p to regulate the expression of EGR1 in cervical cancer.
Fig. 6: EGR1 knockdown rescues the inhibiting impacts of PTENP1 overexpression on cervical cancer cells.

Similar content being viewed by others

References

  1. Jiang H, Huang G, Zhao N, Zhang T, Jiang M, He Y, et al. Long non-coding RNA TPT1-AS1 promotes cell growth and metastasis in cervical cancer via acting AS a sponge for miR-324-5p. J Exp Clin Cancer Res. 2018;37:169.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Zhou B, Yu Y, Yu L, Que B, Qiu R. Sipi soup inhibits cancer-associated fibroblast activation and the inflammatory process by downregulating long non-coding RNA HIPK1-AS. Mol Med Rep. 2018;18:1361–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.

    Article  PubMed  Google Scholar 

  4. Yao J, Li Z, Yang Z, Xue H, Chang H, Zhang X, et al. Long noncoding RNA TOB1-AS1, an epigenetically silenced gene, functioned as a novel tumor suppressor by sponging miR-27b in cervical cancer. Am J Cancer Res. 2018;8:1483–98.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Marth C, Landoni F, Mahner S, McCormack M, Gonzalez-Martin A, Colombo N. Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28:iv72–83.

    Article  CAS  PubMed  Google Scholar 

  6. Rui X, Xu Y, Huang Y, Ji L, Jiang X. lncRNA DLG1-AS1 promotes cell proliferation by competitively binding with miR-107 and up-regulating ZHX1 expression in cervical cancer. Cell Physiol Biochem. 2018;49:1792–803.

    Article  CAS  PubMed  Google Scholar 

  7. Chen J, Shishkin AA, Zhu X, Kadri S, Maza I, Guttman M, et al. Evolutionary analysis across mammals reveals distinct classes of long non-coding RNAs. Genome Biol. 2016;17:19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Wahlestedt C. Targeting long non-coding RNA to therapeutically upregulate gene expression. Nat Rev Drug Discov. 2013;12:433–46.

    Article  CAS  PubMed  Google Scholar 

  9. Ling H, Fabbri M, Calin GA. MicroRNAs and other non-coding RNAs as targets for anticancer drug development. Nat Rev Drug Discov. 2013;12:847–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Xi J, Feng J, Zeng S, Huang P. Long noncoding RNA UFC1 is activated by E2F1 and exerts oncogenic properties by functioning as a ceRNA of FOXP3. Cancer Med. 2018;7:3301–10.

    Article  CAS  PubMed Central  Google Scholar 

  11. Zheng X, Tang H, Zhao X, Sun Y, Jiang Y, Liu Y. Long non-coding RNA FTH1P3 facilitates uveal melanoma cell growth and invasion through miR-224-5p. PLoS ONE. 2017;12;e0184746. https://doi.org/10.1371/journal.pone.0184746.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Yu X, Ye X, Lin H, Feng N, Gao S, Zhang X, et al. Knockdown of long non-coding RNA LCPAT1 inhibits autophagy in lung cancer. Cancer Biol Med. 2018;15:228–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Su C, Shi K, Cheng X, Han Y, Li Y, Yu D, et al. Long noncoding RNA LINC00472 inhibits proliferation and promotes apoptosis of lung adenocarcinoma cells via regulating miR-24-3p/DEDD. Technol Cancer Res Treat. 2018;17:1533033818790490. https://doi.org/10.1177/1533033818790490.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Wei M-M, Zhou Y-C, Wen Z-S, Zhou B, Huang Y-C, Wang G-Z, et al. Long non-coding RNA stabilizes the Y-box-binding protein 1 and regulates the epidermal growth factor receptor to promote lung carcinogenesis. Oncotarget. 2016;7:59556–71.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Wang CH, Li YH, Tian HL, Bao XX, Wang ZM. Long non-coding RNA BLACAT1 promotes cell proliferation, migration and invasion in cervical cancer through activation of Wnt/beta-catenin signaling pathway. Eur Rev Med Pharmacol Sci. 2018;22:3002–9.

    PubMed  Google Scholar 

  16. Gong T, Zheng S, Huang S, Fu S, Zhang X, Pan S, et al. PTENP1 inhibits the growth of esophageal squamous cell carcinoma by regulating SOCS6 expression and correlates with disease prognosis. Mol Carcinog. 2017;56:2610–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zhang R, Guo Y, Ma Z, Ma G, Xue Q, Li F, et al. Long non-coding RNA PTENP1 functions as a ceRNA to modulate PTEN level by decoying miR-106b and miR-93 in gastric cancer. Oncotarget. 2017;8:26079–89.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Chen S, Wang Y, Zhang JH, Xia QJ, Sun Q, Li ZK, et al. Long non-coding RNA PTENP1 inhibits proliferation and migration of breast cancer cells via AKT and MAPK signaling pathways. Oncol Lett. 2017;14:4659–62.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Bydoun M, Sterea A, Weaver ICG, Bharadwaj AD, Waisman DM. A novel mechanism of plasminogen activation in epithelial and mesenchymal cells. Sci Rep. 2018;8:14091.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Zhou L, Liang X, Zhang L, Yang L, Nagao N, Wu H, et al. MiR-27a-3p functions as an oncogene in gastric cancer by targeting BTG2. Oncotarget. 2016;7:51943–54.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Qiao B, He BX, Cai JH, Tao Q, King-Yin Lam A. MicroRNA-27a-3p modulates the Wnt/β-catenin signaling pathway to promote epithelial-mesenchymal transition in oral squamous carcinoma stem cells by targeting SFRP1. Sci Rep. 2017;7:44688.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Shi X, Liu Z, Liu Z, Feng X, Hua F, Hu X, et al. Long noncoding RNA PCAT6 functions as an oncogene by binding to EZH2 and suppressing LATS2 in non-small-cell lung cancer. EBioMedicine. 2018;37:177–87.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Wang L, Sun H, Wang X, Hou N, Zhao L, Tong D, et al. EGR1 mediates miR-203a suppress the hepatocellular carcinoma cells progression by targeting HOXD3 through EGFR signaling pathway. Oncotarget. 2016;7:45302–16.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.

    Article  PubMed  Google Scholar 

  25. Wang H, Wang L, Cao L, Zhang Q, Song Q, Meng Z, et al. Inhibition of autophagy potentiates the anti-metastasis effect of phenethyl isothiocyanate through JAK2/STAT3 pathway in lung cancer cells. Mol Carcinog. 2018;57:522–35.

    Article  CAS  PubMed  Google Scholar 

  26. Liao Y, Cheng S, Xiang J, Luo C. lncRNA CCHE1 increased proliferation, metastasis and invasion of non-small lung cancer cells and predicted poor survival in non-small lung cancer patients. Eur Rev Med Pharmacol Sci. 2018;22:1686–92.

    CAS  PubMed  Google Scholar 

  27. Zhu H, Zheng T, Yu J, Zhou L, Wang L. LncRNA XIST accelerates cervical cancer progression via upregulating Fus through competitively binding with miR-200a. Biomed Pharmacother. 2018;105:789–97.

    Article  CAS  PubMed  Google Scholar 

  28. Ma TT, Zhou LQ, Xia JH, Shen Y, Yan Y, Zhu RH. LncRNA PCAT-1 regulates the proliferation, metastasis and invasion of cervical cancer cells. Eur Rev Med Pharmacol Sci. 2018;22:1907–13.

    PubMed  Google Scholar 

  29. Chan JJ, Tay Y. Noncoding RNA:RNA regulatory networks in cancer. Int J Mol Sci. 2018;19:1310.

    Article  PubMed Central  CAS  Google Scholar 

  30. Sanchez Calle A, Kawamura Y, Yamamoto Y, Takeshita F, Ochiya T. Emerging roles of long non-coding RNA in cancer. Cancer Sci. 2018;109:2093–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Gutschner T, Diederichs S. The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol. 2012;9:703–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Vitiello M, Tuccoli A, Poliseno L. Long non-coding RNAs in cancer: implications for personalized therapy. Cell Oncol. 2015;38:17–28.

    Article  CAS  Google Scholar 

  33. Shi X, Tang X, Su L. Overexpression of long noncoding RNA PTENP1 inhibits cell proliferation and migration via suppression of miR-19b in breast cancer cells. Oncol Res. 2018;26:869–78.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Qian YY, Li K, Liu QY, Liu ZS. Long non-coding RNA PTENP1 interacts with miR-193a-3p to suppress cell migration and invasion through the PTEN pathway in hepatocellular carcinoma. Oncotarget. 2017;8:107859–69.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Yu G, Yao W, Gumireddy K, Li A, Wang J, Xiao W, et al. Pseudogene PTENP1 functions as a competing endogenous RNA to suppress clear-cell renal cell carcinoma progression. Mol Cancer Ther. 2014;13:3086–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Liu H, Liu S, Liu L, Ma R, Gao P. EGR1-mediated transcription of lncRNA-HNF1A-AS1 promotes cell cycle progression in gastric cancer. Cancer Res. 2018;78:5877–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Oben KZ, Gachuki BW, Alhakeem SS, McKenna MK, Liang Y, St. Clair DK, et al. Radiation induced apoptosis of murine bone marrow cells is independent of early growth response 1 (EGR1). PLoS ONE. 2017;12:e0169767.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Tarcic G, Avraham R, Pines G, Amit I, Shay T, Lu Y, et al. EGR1 and the ERK-ERF axis drive mammary cell migration in response to EGF. FASEB J. 2012;26:1582–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Wang D, Guan M, Zheng Z, Li W, Lyv F, Pang R, et al. Transcription factor Egr1 is involved in high glucose-induced proliferation and fibrosis in rat glomerular mesangial cells. Cell. Physiol. Biochem. 2015;36:2093–107.

    Article  PubMed  CAS  Google Scholar 

  40. Mohamad T, Kazim N, Adhikari A, Davie JK. EGR1 interacts with TBX2 and functions as a tumor suppressor in rhabdomyosarcoma. Oncotarget. 2018:9:18084–98.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Wang H, Song X, Zhang H, Zhang J, Shen X, Zhou Y, et al. Potentiation of tumor radiotherapy by a radiation-inducible oncolytic and oncoapoptotic adenovirus in cervical cancer xenografts. Int. J. Cancer. 2012;130:443–53.

    Article  CAS  PubMed  Google Scholar 

  42. Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi PP. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell. 2011;146:353–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Yang S, Ning Q, Zhang G, Sun H, Wang Z, Li Y. Construction of differential mRNA-lncRNA crosstalk networks based on ceRNA hypothesis uncover key roles of lncRNAs implicated in esophageal squamous cell carcinoma. Oncotarget. 2016;7:85728–40.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This study was funded by Luoyang Science and Technology Key Project (No. 1503006A-6).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Li Tan.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, C., Wang, F. & Tan, L. Role and the molecular mechanism of lncRNA PTENP1 in regulating the proliferation and invasion of cervical cancer cells. Gene Ther 29, 464–475 (2022). https://doi.org/10.1038/s41434-020-00189-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41434-020-00189-8

This article is cited by

Search

Quick links