Skip to main content

Advertisement

SpringerLink
Log in

The investigation of circRNA profiling reveals the regulatory role of the hsa_circ_0000375/miR-7706 pathway in breast cancer

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Background

Circular RNAs (circRNAs) take an effect on tumorigenesis and progression. However, circRNAs have not been systematically identified in breast cancer (BC) as crucial regulators in multitudinous biological processes. This study is conducted to explore novel circRNAs in BC and the corresponding mechanisms of their action.

Methods

The circRNA expression profile and RNA-sequencing data about BC were respectively downloaded from public database. Differentially expressed circRNAs, miRNAs, and mRNAs were identified by fold change filtering. The competing endogenous RNAs (ceRNAs) network was established based on the relationship between circular RNAs, miRNAs and mRNAs. GO and KEGG enrichment analysis of the overlapped genes were carried out to predict the potential functions and mechanisms of circRNAs in BC. The CytoHubba plugin in Cytoscape was applied to identify the hub genes from the PPI regulatory network. Kaplan–Meier plotter was used to perform survival analysis of these hub genes further. Real-time PCR was performed to test the expression of circRNA in BC tissues. Cell function studies including transwell analysis and CCK-8 analysis were used to investigate circRNAs’ biological functions.

Results

A total of seven circRNAs exhibiting differential expression were identified in this study. After the intersection between the predicted target miRNA and the down-regulated differential miRNAs (DEmiRNAs), circRNA-miRNA interactions involving 3 circRNAs and 4 miRNAs were identified. Venn diagram was utilized to intersect the predicted target genes of the 4 miRNAs and the down-regulated differential genes in BC, and 149 overlapped genes were screened out ulteriorly. Additionally, we built a protein-protein interaction (PPI) network and selected six hub genes. Moreover, the survival data of BC patients suggested that low expression of ADIPOQ, LPL and LEP were significantly correlated with poor prognosis. Results from real-time PCR indicated that hsa_circ_0000375 was significantly down-regulated in breast cancer tissues. Functional in vitro experiments showed that over-expression of hsa_circ_0000375 can restrain proliferation, migration and invasion abilities of breast cancer cells. Further verification indicated that hsa_circ_0000375 exerted its anti-oncogene effect via sponge of miR-7706.

Conclusions

This study constructed and analyzed a circRNA-associated ceRNA regulatory network and uncovered that hsa_circ_0000375 exerted its anti-oncogene effect via sponge of miR-7706.

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

Data Availability

All data in this study are available from the corresponding author upon request.

References

  1. Cardoso F, Paluch-Shimon S, Senkus E, Curigliano G, Aapro MS et al (2020) 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol 31:1623–1649

    Article  CAS  PubMed  Google Scholar 

  2. Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J et al (2013) Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495:333–338

    Article  CAS  PubMed  Google Scholar 

  3. Jeck WR, Sharpless NE (2014) Detecting and characterizing circular RNAs. Nat Biotechnol 32:453–461

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B et al (2013) Natural RNA circles function as efficient microRNA sponges. Nature 495:384–388

    Article  CAS  PubMed  Google Scholar 

  5. Chen Q, Wang H, Li Z, Li F, Liang L et al (2022) Circular RNA ACTN4 promotes intrahepatic cholangiocarcinoma progression by recruiting YBX1 to initiate FZD7 transcription. J Hepatol 76:135–147

    Article  CAS  PubMed  Google Scholar 

  6. Wu P, Hou X, Peng M, Deng X, Yan Q et al (2023) Circular RNA circRILPL1 promotes nasopharyngeal carcinoma malignant progression by activating the Hippo-YAP signaling pathway. Cell Death Differ 30:1679–1694

    Article  CAS  PubMed  Google Scholar 

  7. He P, Liu F, Wang Z, Gong H, Zhang M et al (2022) CircKIF4A enhances osteosarcoma proliferation and metastasis by sponging MiR-515-5p and upregulating SLC7A11. Mol Biol Rep 49:4525–4535

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Liu L, Gu M, Ma J, Wang Y, Li M et al (2022) CircGPR137B/miR-4739/FTO feedback loop suppresses tumorigenesis and metastasis of hepatocellular carcinoma. Mol Cancer 21:149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Chen J, Yang J, Fei X, Wang X, Wang K (2021) CircRNA ciRS-7: a Novel Oncogene in multiple cancers. Int J Biol Sci 17:379–389

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hu Z, Chen J, Wang M, Weng W, Chen Y et al (2022) Rheumatoid arthritis fibroblast-like synoviocytes maintain tumor-like biological characteristics through ciRS-7-dependent regulation of miR-7. Mol Biol Rep 49:8473–8483

    Article  CAS  PubMed  Google Scholar 

  11. Yu Q, Chen W, Li Y, He J, Wang Y et al (2022) The novel circular RNA HIPK3 accelerates the proliferation and invasion of hepatocellular carcinoma cells by sponging the micro RNA-124 or micro RNA-506/pyruvate dehydrogenase kinase 2 axis. Bioengineered 13:4717–4729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wang S, Tong H, Su T, Zhou D, Shi W et al (2021) CircTP63 promotes cell proliferation and invasion by regulating EZH2 via sponging miR-217 in gallbladder cancer. Cancer Cell Int 21:608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Huang W, Yang Y, Wu J, Niu Y, Yao Y et al (2020) Circular RNA cESRP1 sensitises small cell lung cancer cells to chemotherapy by sponging mir-93-5p to inhibit TGF-beta signalling. Cell Death Differ 27:1709–1727

    Article  CAS  PubMed  Google Scholar 

  14. Li J, Gao X, Zhang Z, Lai Y, Lin X et al (2021) CircCD44 plays oncogenic roles in triple-negative breast cancer by modulating the miR-502-5p/KRAS and IGF2BP2/Myc axes. Mol Cancer 20:138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Vo JN, Cieslik M, Zhang Y, Shukla S, Xiao L et al (2019) The Landscape of circular RNA in Cancer. Cell 176:869–881e813

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Liu F, Sang Y, Zheng Y, Gu L, Meng L et al (2022) circRNF10 regulates tumorigenic Properties and Natural Killer cell-mediated cytotoxicity against breast Cancer through the miR-934/PTEN/PI3k-Akt Axis. Cancers (Basel) 14

  17. Ding F, Lu L, Wu C, Pan X, Liu B et al (2022) circHIPK3 prevents cardiac senescence by acting as a scaffold to recruit ubiquitin ligase to degrade HuR. Theranostics 12:7550–7566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Li Z, Huang C, Bao C, Chen L, Lin M et al (2015) Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol 22:256–264

    Article  PubMed  Google Scholar 

  19. Arnaiz E, Sole C, Manterola L, Iparraguirre L, Otaegui D et al (2019) CircRNAs and cancer: biomarkers and master regulators. Semin Cancer Biol 58:90–99

    Article  CAS  PubMed  Google Scholar 

  20. Pan Z, Zheng J, Zhang J, Lin J, Lai J et al (2022) A Novel protein encoded by Exosomal CircATG4B induces Oxaliplatin Resistance in Colorectal Cancer by promoting Autophagy. Adv Sci (Weinh) 9:e2204513

    Article  PubMed  Google Scholar 

  21. Song R, Guo P, Ren X, Zhou L, Li P et al (2023) A novel polypeptide CAPG-171aa encoded by circCAPG plays a critical role in triple-negative breast cancer. Mol Cancer 22:104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Liang Y, Cen J, Huang Y, Fang Y, Wang Y et al (2022) CircNTNG1 inhibits renal cell carcinoma progression via HOXA5-mediated epigenetic silencing of slug. Mol Cancer 21:224

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Zhong Y, Du Y, Yang X, Mo Y, Fan C et al (2018) Circular RNAs function as ceRNAs to regulate and control human cancer progression. Mol Cancer 17:79

    Article  PubMed  PubMed Central  Google Scholar 

  24. Cortes-Lopez M, Miura P (2016) Emerging functions of circular RNAs. Yale J Biol Med 89:527–537

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Ghafouri-Fard S, Hussen BM, Taheri M, Ayatollahi SA (2021) Emerging role of circular RNAs in breast cancer. Pathol Res Pract 223:153496

    Article  CAS  PubMed  Google Scholar 

  26. Yin TF, Zhao DY, Zhou YC, Wang QQ, Yao SK (2021) Identification of the circRNA-miRNA-mRNA regulatory network and its prognostic effect in colorectal cancer. World J Clin Cases 9:4520–4541

    Article  PubMed  PubMed Central  Google Scholar 

  27. Yin TF, Du SY, Zhao DY, Sun XZ, Zhou YC et al (2022) Identification of circ_0000375 and circ_0011536 as novel diagnostic biomarkers of colorectal cancer. World J Clin Cases 10:3352–3368

    Article  PubMed  PubMed Central  Google Scholar 

  28. Su Y, Sun Y, Tang Y, Li H, Wang X et al (2021) Circulating miR-19b-3p as a Novel Prognostic Biomarker for Acute Heart failure. J Am Heart Assoc 10:e022304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Shen Y, Wang L, Wu Y, Ou Y, Lu H et al (2021) A novel diagnostic signature based on three circulating exosomal mircoRNAs for chronic obstructive pulmonary disease. Exp Ther Med 22:717

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Wang F, Dai M, Chen H, Li Y, Zhang J et al (2018) Prognostic value of hsa-mir-299 and hsa-mir-7706 in hepatocellular carcinoma. Oncol Lett 16:815–820

    PubMed  PubMed Central  Google Scholar 

  31. Manupati K, Yeeravalli R, Kaushik K, Singh D, Mehra B et al (2021) Activation of CD44-Lipoprotein lipase axis in breast cancer stem cells promotes tumorigenesis. Biochim Biophys Acta Mol Basis Dis 1867:166228

    Article  CAS  PubMed  Google Scholar 

  32. Almanza A, Mnich K, Blomme A, Robinson CM, Rodriguez-Blanco G et al (2022) Regulated IRE1alpha-dependent decay (RIDD)-mediated reprograming of lipid metabolism in cancer. Nat Commun 13:2493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Chung SJ, Nagaraju GP, Nagalingam A, Muniraj N, Kuppusamy P et al (2017) ADIPOQ/adiponectin induces cytotoxic autophagy in breast cancer cells through STK11/LKB1-mediated activation of the AMPK-ULK1 axis. Autophagy 13:1386–1403

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

No.

Funding

This work was supported by the 2023 Medical science research key project [number 20230148] and the Hebei Provincial Department of Education’s postgraduate innovation ability training funding project. [number CXZZBS2023102].

Author information

Author notes

  1. Haoqi Wang, Fei Liu contributed equally to this work.

Authors and Affiliations

  1. Breast Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, 050017, Hebei, P.R. China

    Haoqi Wang, Wei Gao, Shan Yang, Yunzhe Mi, Xi Zhang & Cuizhi Geng

  2. Research Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, 050017, Hebei, P.R. China

    Fei Liu

  3. Radiology Department, the Fourth Hospital of Hebei Medical University, Shijiazhuang, 050017, Hebei, P.R. China

    Jing Xue

  4. Medical insurance center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, 050017, Hebei, P.R. China

    Yaping Liu

  5. Gland Surgery, the Hebei Province People’s Hospital, Shijiazhuang, 050000, Hebei, P.R. China

    Shan Gao

Authors
  1. Haoqi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fei Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jing Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yaping Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wei Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shan Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yunzhe Mi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xi Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Shan Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Cuizhi Geng
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

H.W. and F.L. conducted data analysis and validation. S.G. and C.G. conceived the study and drafted the manuscript. J.X., Y.L., W.G. and S.Y. performed the experiments. All authors have read and agreed to the final manuscript. S.G. and C.G. confirm the authenticity of all the raw data. All authors reviewed the manuscript.

Corresponding authors

Correspondence to Shan Gao or Cuizhi Geng.

Ethics declarations

Competing interests

The authors declare no competing interests.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

Ethical approval for this study was obtained from the Research Ethics Committee of the Fourth Hospital of Hebei Medical University (number 2019MEC057).

Consent of publication

All the authors have consent to publish.

Consent to participant

All participants included in the study were provided with informed consent.

Additional information

Publisher’s Note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, H., Liu, F., Xue, J. et al. The investigation of circRNA profiling reveals the regulatory role of the hsa_circ_0000375/miR-7706 pathway in breast cancer. Mol Biol Rep 50, 9993–10004 (2023). https://doi.org/10.1007/s11033-023-08798-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-023-08798-3

Keywords

Search

Navigation