Skip to main content

Advertisement

SpringerLink
Log in

CircRNA VPRBP inhibits tumorigenicity of cervical cancer via miR-93-5p/FRMD6 axis

  • Gynecologic Oncology: Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Background

Cervical cancer is a malignant tumor that threatens the life and health of women. Circular RNA (circRNA) is a research hotspot in human diseases including cervical cancer. However, the research of circRNA viral protein R-binding protein (circ_VPRBP) in cervical cancer is blank.

Methods

Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of target genes in cervical cancer tissues and cells. The expression of related proteins was detected by western blot. The localization of circ_VPRBP was detected by nuclear cytoplasmic separation, and the stability of circ_VPRBP was verified by actinomycin D. After transfection with oligonucleotides and/or plasmids, cell proliferation, migration, invasion and apoptosis were detected by 3-(4, 5-dimethylthiazol-2-yl) -2, 5-diphenyl-2-H-tetrazolium bromide (MTT), colony formation, 5-ethynyl-2’-deoxyuridine (EdU), transwell, or flow cytometry assays. Mechanistically, the interaction between microRNA-93-5p (miR-93-5p) and circ_VPRBP/FERM domain containing 6 (FRMD6) was verified by dual luciferase reporter assay. Animal experiment was conducted to investigate the role of circ_VPRBP in vivo.

Results

Circ_VPRBP was down-regulated in cervical cancer tissues and cells, and overexpression of circ_VPRBP inhibited proliferation and promoted apoptosis of Caski and C33A cells. MiR-93-5p was a target of circ_VPRBP, and miR-93-5p mimic reversed the effect of circ_VPRBP on cell behavior. FRMD6 was a downstream target of miR-93-5p, and down-regulated FRMD6 reversed the cell viability, migration and invasion of cervical cancer cells inhibited by anti-miR-93-5p. Circ_VPRBP inhibited tumor growth by regulating miR-93-5p and FRMD6 in vivo.

Conclusion

Circ_VPRBP inhibited cell proliferation, migration and invasion and promoted cell apoptosis of cervical cancer cells by regulating miR-93-5p/FRMD6 axis.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Availability of data and material

Not Applicable.

Code availability

Not Applicable.

References

  1. Bedell SL, Goldstein LS, Goldstein AR, Goldstein AT. Cervical Cancer Screening: Past, Present, and Future. Sex Med Rev. 2020;8(1):28–37.

    Article  Google Scholar 

  2. Gupta S, Kumar P, Das BC. HPV: Molecular pathways and targets. Curr Probl Cancer. 2018;42(2):161–74.

    Article  Google Scholar 

  3. Estevao D, Costa NR. Gil da Costa RM, Medeiros R: Hallmarks of HPV carcinogenesis: The role of E6, E7 and E5 oncoproteins in cellular malignancy. Biochim Biophys Acta Gene Regul Mech. 2019;1862(2):153–62.

    Article  CAS  Google Scholar 

  4. Thapa N, Maharjan M, Xiong Y, Jiang D, Nguyen TP, Petrini MA, Cai H. Impact of cervical cancer on quality of life of women in Hubei, China. Sci Rep. 2018;8(1):11993.

    Article  Google Scholar 

  5. Wright JD, Huang Y, Ananth CV, Tergas AI, Duffy C, Deutsch I, Burke WM, Hou JY, Neugut AI, Hershman DL. Influence of treatment center and hospital volume on survival for locally advanced cervical cancer. Gynecol Oncol. 2015;139(3):506–12.

    Article  Google Scholar 

  6. Li XY, Wang X. The role of human cervical cancer oncogene in cancer progression. Int J Clin Exp Med. 2015;8(6):8363–8.

    PubMed  PubMed Central  Google Scholar 

  7. Kristensen LS, Andersen MS, Stagsted LVW, Ebbesen KK, Hansen TB, Kjems J. The biogenesis, biology and characterization of circular RNAs. Nat Rev Genet. 2019;20(11):675–91.

    Article  CAS  Google Scholar 

  8. Zhong Y, Du Y, Yang X, Mo Y, Fan C, Xiong F, Ren D, Ye X, Li C, Wang Y, et al. Circular RNAs function as ceRNAs to regulate and control human cancer progression. Mol Cancer. 2018;17(1):79.

    Article  Google Scholar 

  9. Verduci L, Strano S, Yarden Y, Blandino G. The circRNA-microRNA code: emerging implications for cancer diagnosis and treatment. Mol Oncol. 2019;13(4):669–80.

    Article  Google Scholar 

  10. Chaichian S, Shafabakhsh R, Mirhashemi SM, Moazzami B, Asemi Z. Circular RNAs: A novel biomarker for cervical cancer. J Cell Physiol. 2020;235(2):718–24.

    Article  CAS  Google Scholar 

  11. Chen RX, Liu HL, Yang LL, Kang FH, Xin LP, Huang LR, Guo QF, Wang YL. Circular RNA circRNA_0000285 promotes cervical cancer development by regulating FUS. Eur Rev Med Pharmacol Sci. 2019;23(20):8771–8.

    PubMed  Google Scholar 

  12. Zhang S, Chen Z, Sun J, An N, Xi Q. CircRNA hsa_circRNA_0000069 promotes the proliferation, migration and invasion of cervical cancer through miR-873-5p/TUSC3 axis. Cancer Cell Int. 2020;20:287.

    Article  CAS  Google Scholar 

  13. Gao C, Zhou C, Zhuang J, Liu L, Liu C, Li H, Liu G, Wei J, Sun C. MicroRNA expression in cervical cancer: Novel diagnostic and prognostic biomarkers. J Cell Biochem. 2018;119(8):7080–90.

    Article  CAS  Google Scholar 

  14. Sun XY, Han XM, Zhao XL, Cheng XM, Zhang Y. MiR-93-5p promotes cervical cancer progression by targeting THBS2/MMPS signal pathway. Eur Rev Med Pharmacol Sci. 2019;23(12):5113–21.

    PubMed  Google Scholar 

  15. Zhang P-F, Wei C-Y, Huang X-Y, Peng R, Yang X, Lu J-C, Zhang C, Gao C, Cai J-B, Gao P-T, et al. Circular RNA circTRIM33-12 acts as the sponge of MicroRNA-191 to suppress hepatocellular carcinoma progression. Mol Cancer. 2019;18(1):105.

    Article  Google Scholar 

  16. Cao Z, Zhang G, Xie C, Zhou Y. MiR-34b regulates cervical cancer cell proliferation and apoptosis. Artif Cells Nanomed Biotechnol. 2019;47(1):2042–7.

    Article  CAS  Google Scholar 

  17. Li X, Li Y, Han Y, Dong B, Liu D, Che L, Liu Y, Wang Y. miR-205 Promotes Apoptosis of Cervical Cancer Cells and Enhances Drug Sensitivity of Cisplatin by Inhibiting YAP1. Cancer Biother Radiopharm. 2020;35(5):338–44.

    Article  CAS  Google Scholar 

  18. Li P, Wang J, Zhi L, Cai F. Linc00887 suppresses tumorigenesis of cervical cancer through regulating the miR-454-3p/FRMD6-Hippo axis. Cancer Cell Int. 2021;21(1):33.

    Article  CAS  Google Scholar 

  19. Patop IL, Kadener S. circRNAs in Cancer. Curr Opin Genet Dev. 2018;48:121–7.

    Article  CAS  Google Scholar 

  20. Chen S, Yang X, Yu C, Zhou W, Xia Q, Liu Y, Chen Q, Chen X, Lv Y, Lin Y. The Potential of circRNA as a Novel Diagnostic Biomarker in Cervical Cancer. J Oncol. 2021;2021:5529486.

    PubMed  PubMed Central  Google Scholar 

  21. Yi Y, Liu Y, Wu W, Wu K, Zhang W. Reconstruction and analysis of circRNAmiRNAmRNA network in the pathology of cervical cancer. Oncol Rep. 2019;41(4):2209–25.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Chen X, Liu J, Zhang Q, Liu B, Cheng Y, Zhang Y, Sun Y, Ge H, Liu Y. Exosome-mediated transfer of miR-93-5p from cancer-associated fibroblasts confer radioresistance in colorectal cancer cells by downregulating FOXA1 and upregulating TGFB3. J Exp Clin Cancer Res. 2020;39(1):65.

    Article  CAS  Google Scholar 

  23. Cai Y, Ruan W, Ding J, Wei N, Wang J, Zhang H, Ma N, Weng G, Su WK, Lin Y, et al. miR‑93‑5p regulates the occurrence and development of esophageal carcinoma epithelial cells by targeting TGFβR2. Int J Mol Med. 2021;47(3).

  24. Yang Y, Jia B, Zhao X, Wang Y, Ye W. miR-93-5p may be an important oncogene in prostate cancer by bioinformatics analysis. J Cell Biochem. 2019;120(6):10463–83.

    Article  CAS  Google Scholar 

  25. Beck J, Kressel M. FERM domain-containing protein 6 identifies a subpopulation of varicose nerve fibers in different vertebrate species. Cell Tissue Res. 2020;381(1):13–24.

    Article  CAS  Google Scholar 

  26. Haldrup J, Strand SH, Cieza-Borrella C, Jakobsson ME, Riedel M, Norgaard M, Hedensted S, Dagnaes-Hansen F, Ulhoi BP, Eeles R, et al. FRMD6 has tumor suppressor functions in prostate cancer. Oncogene. 2021;40(4):763–76.

    Article  CAS  Google Scholar 

  27. Guan C, Chang Z, Gu X, Liu R. MTA2 promotes HCC progression through repressing FRMD6, a key upstream component of hippo signaling pathway. Biochem Biophys Res Commun. 2019;515(1):112–8.

    Article  CAS  Google Scholar 

  28. Xu Y, Wang K, Yu Q. FRMD6 inhibits human glioblastoma growth and progression by negatively regulating activity of receptor tyrosine kinases. Oncotarget. 2016;7(43):70080–91.

    Article  Google Scholar 

  29. Wang W, Zhao C, Quan F, Zhang P, Shao Y, Liu L. FERM domain-containing protein 6 exerts a tumor-inhibiting role in thyroid cancer by antagonizing oncogenic YAP1. 2021.

  30. Li P, Wang J, Zhi L, Cai F. Linc00887 suppresses tumorigenesis of cervical cancer through regulating the miR-454–3p/FRMD6-Hippo axis. Cancer Cell Int. 2021;21(1):33.

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by:

1. A special free exploration basic project for local science and technology development guided by the central government in 2020 (2020ZYD056).

2. Nanchong City School Science and Technology Strategic Cooperation Special Fund Project (18SXHZ0126).

Author information

Author notes

  1. Lunhua Shen and Jiafeng Dang contributed equally to this work.

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Affiliated Hospital of North Sichuan Medical College, No. 1, Maoyuan South Road, Shunqing District, Nanchong City, 637000, Sichuan Province, China

    Lunhua Shen, Shengfeng Liu & Dacheng Qu

  2. Non-Invasive and Microinvasive Laboratory of Gynecology, Affiliated Hospital of North Sichuan Medical College, No. 1, Maoyuan South Road, Shunqing District, Nanchong City, 637000, Sichuan Province, China

    Lunhua Shen & Dacheng Qu

  3. Department of Obstetrics and Gynecology, Pidu District People’s Hospital, Chengdu City, Sichuan Province, China

    Jiafeng Dang

  4. Department of Clinical Medicine, North Sichuan Medical College, Nanchong City, Sichuan Province, China

    Biao Xian

  5. Department of Obstetrics and Gynecology, People’s Hospital of Lezhi County, Sichuan Province, Ziyang City, Sichuan Province, China

    Yan Deng

Authors
  1. Lunhua Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jiafeng Dang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shengfeng Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Biao Xian
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yan Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dacheng Qu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dacheng Qu.

Ethics declarations

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethics approval

Written informed consents were obtained from all participants, and this study was permitted by the Ethics Committee of Affiliated Hospital of North Sichuan Medical College.

Consent to participate

Not Applicable.

Consent for publication

Not Applicable.

Additional information

Publisher’s Note

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

Highlight

(1) Circ_VPRBP was down-regulated in cervical cancer tissue and cells.

(2) Circ_VPRBP functioned as a sponge of miR-93-5p.

(3) FRMD6 was a target of miR-93-5p.

(4) Circ_VPRBP regulated FRMD6 expression by sponging miR-93-5p.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shen, L., Dang, J., Liu, S. et al. CircRNA VPRBP inhibits tumorigenicity of cervical cancer via miR-93-5p/FRMD6 axis. Reprod. Sci. 29, 2251–2264 (2022). https://doi.org/10.1007/s43032-022-00923-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43032-022-00923-0

Keywords

Search

Navigation