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:

RHPN1-AS1 promotes cell proliferation and migration via miR-665/Akt3 in ovarian cancer

Abstract

Recent efforts have revealed that long non-coding RNAs exert crucial roles in cancer initiation and progression. RHPN1-AS1 is a 2030 bp transcript from human chromosome 8q24, and involved in tumorigenesis in uveal melanoma and non-small cell lung cancer, but it remains unknown in ovarian cancer. This study focused on the role of RHPN1-AS1 in ovarian cancer and found that RHPN1-AS1 was up-regulated in ovarian cancer tissues and cell lines. Overexpression of RHPN1-AS1 promoted ovarian cancer cell proliferation, migration, and invasion. Mechanistically, overexpression of RHPN1-AS1 decreased the expression of miR-665 and subsequently promoted the expression of Akt3 at posttranscriptional level. Taken together, RHPN1-AS1 positively regulated the expression of Akt3 through sponging miR-665, and exerted an oncogenic role in ovarian cancer progression, and indicates that RHPN1-AS1 may be a potential therapeutic target in ovarian 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: Up-regulated expression of RHPN1-AS1 in ovarian cancer tissue and cell lines.
Fig. 2: Effects of RHPN1-AS1 on ovarian cancer cell proliferation, migration, and invasion.
Fig. 3: RHPN1-AS1 interacts with miR-665.
Fig. 4: RHPN1-AS1 exerted roles through regulating miR-665 level.
Fig. 5: RHPN1-AS1 up-regulates Akt3 expression by competitively binding to miR-665.
Fig. 6: Knockdown of RHPN1-AS1 impaired ovarian cancer cell growth in vivo.

Similar content being viewed by others

References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:7–34.

    Article  Google Scholar 

  2. Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66:115–32.

    Article  Google Scholar 

  3. Berek JS, Kehoe ST, Kumar L, Friedlander M. Cancer of the ovary, fallopian tube, and peritoneum. Int J Gynaecol Obstet. 2018;143(Suppl 2):59–78.

    Article  Google Scholar 

  4. Cannistra SA. Cancer of the ovary. N Engl J Med. 2004;351:2519–29.

    Article  CAS  Google Scholar 

  5. Ji K, Ye L, Mason MD, Jiang WG. The Kiss-1/Kiss-1R complex as a negative regulator of cell motility and cancer metastasis (Review). Int J Mol Med. 2013;32:747–54.

    Article  CAS  Google Scholar 

  6. Peng WX, Koirala P, Mo YY. LncRNA-mediated regulation of cell signaling in cancer. Oncogene. 2017;36:5661–7.

    Article  CAS  Google Scholar 

  7. Loewen G, Jayawickramarajah J, Zhuo Y, Shan B. Functions of lncRNA HOTAIR in lung cancer. J Hematol Oncol. 2014;7:90.

    Article  Google Scholar 

  8. Hao NB, He YF, Li XQ, Wang K, Wang RL. The role of miRNA and lncRNA in gastric cancer. Oncotarget. 2017;8:81572–82.

    Article  Google Scholar 

  9. Zhu J, Fu H, Wu Y, Zheng X. Function of lncRNAs and approaches to lncRNA–protein interactions. Sci China Life Sci. 2013;56:876–85.

    Article  CAS  Google Scholar 

  10. Li X, Zhang X, Yang C, Cui S, Shen Q, Xu S. The lncRNA RHPN1-AS1 downregulation promotes gefitinib resistance by targeting miR-299-3p/TNFSF12 pathway in NSCLC. Cell Cycle. 2018;17:1772–83.

    Article  CAS  Google Scholar 

  11. Lu L, Yu X, Zhang L, Ding X, Pan H, Wen X, et al. The long non-coding RNA RHPN1-AS1 promotes uveal melanoma progression. Int J Mol Sci. 2017;18:226.

    Article  Google Scholar 

  12. Cai Y, Yu X, Hu S, Yu J. A brief review on the mechanisms of miRNA regulation. Genomics Proteom Bioinforma. 2009;7:147–54.

    Article  CAS  Google Scholar 

  13. Fabian MR, Sonenberg N. The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC. Nat Struct Mol Biol. 2012;19:586–93.

    Article  CAS  Google Scholar 

  14. Hu Y, Yang C, Yang S, Cheng F, Rao J, Wang X. miR-665 promotes hepatocellular carcinoma cell migration, invasion, and proliferation by decreasing Hippo signaling through targeting PTPRB. Cell Death Dis. 2018;9:954.

    Article  Google Scholar 

  15. Sun WC, Pei L. rno-miR-665 targets BCL2L1 (Bcl-xl) and increases vulnerability to propofol in developing astrocytes. J Neurochem. 2016;138:233–42.

    Article  CAS  Google Scholar 

  16. Sun WC, Liang ZD, Pei L. Propofol-induced rno-miR-665 targets BCL2L1 and influences apoptosis in rodent developing hippocampal astrocytes. Neurotoxicology. 2015;51:87–95.

    Article  CAS  Google Scholar 

  17. Prashad N. miR-665 targets c-MYC and HDAC8 to inhibit murine neuroblastoma cell growth. Oncotarget. 2018;9:33186–201.

    Article  Google Scholar 

  18. Qu Z, Wu J, Ji A, Qiang G, Jiang Y, Jiang C, et al. Exosomal miR-665 as a novel minimally invasive biomarker for hepatocellular carcinoma diagnosis and prognosis. Oncotarget. 2017;8:80666–78.

    Article  Google Scholar 

  19. Liu J, Jiang Y, Wan Y, Zhou S, Thapa S, Cheng W. MicroRNA665 suppresses the growth and migration of ovarian cancer cells by targeting HOXA10. Mol Med Rep. 2018;18:2661–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Marin-Bejar O, Marchese FP, Athie A, Sanchez Y, Gonzalez J, Segura V, et al. Pint lincRNA connects the p53 pathway with epigenetic silencing by the Polycomb repressive complex 2. Genome Biol. 2013;14:R104.

    Article  Google Scholar 

  21. Liu D, Li Y, Luo G, Xiao X, Tao D, Wu X, et al. LncRNA SPRY4-IT1 sponges miR-101-3p to promote proliferation and metastasis of bladder cancer cells through up-regulating EZH2. Cancer Lett. 2017;388:281–91.

    Article  CAS  Google Scholar 

  22. Chen G, Peng L, Zhu Z, Du C, Shen Z, Zang R, et al. LncRNA AFAP1-AS functions as a competing endogenous RNA to regulate RAP1B expression by sponging miR-181a in the HSCR. Int J Med Sci. 2017;14:1022–30.

    Article  CAS  Google Scholar 

  23. Rask L, Balslev E, Jorgensen S, Eriksen J, Flyger H, Moller S, et al. High expression of miR-21 in tumor stroma correlates with increased cancer cell proliferation in human breast cancer. APMIS. 2011;119:663–73.

    Article  Google Scholar 

  24. Gordon MA, Babbs B, Cochrane DR, Bitler BG, Richer JK. The long non-coding RNA MALAT1 promotes ovarian cancer progression by regulating RBFOX2-mediated alternative splicing. Mol Carcinog. 2019;58:196–205.

    Article  CAS  Google Scholar 

  25. Mu Y, Li N, Cui YL. The lncRNA CCAT1 upregulates TGFbetaR1 via sponging miR-490-3p to promote TGFbeta1-induced EMT of ovarian cancer cells. Cancer Cell Int. 2018;18:145.

    Article  Google Scholar 

  26. Liu X, Wen J, Wang H, Wang Y. Long non-coding RNA LINC00460 promotes epithelial ovarian cancer progression by regulating microRNA-338-3p. Biomed Pharmacother = Biomed Pharmacother. 2018;108:1022–8.

    Article  CAS  Google Scholar 

  27. Zhou B, Guo W, Sun C, Zhang B, Zheng F. Linc00462 promotes pancreatic cancer invasiveness through the miR-665/TGFBR1-TGFBR2/SMAD2/3 pathway. Cell Death Dis. 2018;9:706.

    Article  Google Scholar 

  28. Wu R, Ruan J, Sun Y, Liu M, Sha Z, Fan C, et al. Long non-coding RNA HIF1A-AS2 facilitates adipose-derived stem cells (ASCs) osteogenic differentiation through miR-665/IL6 axis via PI3K/Akt signaling pathway. Stem Cell Res Ther. 2018;9:348.

    Article  CAS  Google Scholar 

  29. Robey RB, Hay N. Is Akt the “Warburg kinase”?-Akt-energy metabolism interactions and oncogenesis. Semin Cancer Biol. 2009;19:25–31.

    Article  CAS  Google Scholar 

  30. Liu W, Zhou Z, Zhang Q, Rong Y, Li L, Luo Y, et al. Overexpression of miR-1258 inhibits cell proliferation by targeting AKT3 in osteosarcoma. Biochem Biophys Res Commun. 2019;510:479–86.

    Article  CAS  Google Scholar 

  31. Wang YX, Zhu HF, Zhang ZY, Ren F, Hu YH. MiR-384 inhibits the proliferation of colorectal cancer by targeting AKT3. Cancer Cell Int. 2018;18:124.

    Article  Google Scholar 

  32. Lin HP, Lin CY, Huo C, Jan YJ, Tseng JC, Jiang SS, et al. AKT3 promotes prostate cancer proliferation cells through regulation of Akt, B-Raf, and TSC1/TSC2. Oncotarget. 2015;6:27097–112.

    Article  Google Scholar 

  33. Phung TL, Du W, Xue Q, Ayyaswamy S, Gerald D, Antonello Z, et al. Akt1 and akt3 exert opposing roles in the regulation of vascular tumor growth. Cancer Res. 2015;75:40–50.

    Article  CAS  Google Scholar 

  34. Grottke A, Ewald F, Lange T, Norz D, Herzberger C, Bach J, et al. Downregulation of AKT3 increases migration and metastasis in triple negative breast cancer cells by upregulating S100A4. PLoS ONE. 2016;11:e0146370.

    Article  Google Scholar 

Download references

Funding

This study was supported by Shaanxi Provincial Key R&D Program: General Project—Social Development Area, Fund number: 2017SF-016.

Author information

Authors and Affiliations

Authors

Contributions

XH and JZ conceived the experiments; JZ, TY, and CL performed the experiments; JZ and JJ analyzed the data; XH and JZ wrote the manuscript. All authors read and approved the final version of manuscript.

Corresponding author

Correspondence to Xiaobing Han.

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

Zhao, J., Yang, T., Ji, J. et al. RHPN1-AS1 promotes cell proliferation and migration via miR-665/Akt3 in ovarian cancer. Cancer Gene Ther 28, 33–41 (2021). https://doi.org/10.1038/s41417-020-0180-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41417-020-0180-0

This article is cited by

Search

Quick links