Skip to main content

Advertisement

SpringerLink
Log in

Circ_RPPH1 regulates glioma cell malignancy by binding to miR-627-5p/miR-663a to induce SDC1 expression

  • Original Article
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

Background

Recent studies revealed the key role of circular RNA (circRNA) in glioma progression. However, the effect of circ_0000520, also named as circRNA ribonuclease P RNA component H1 (circ_RPPH1), in glioma development was unknown. The study aimed to reveal the role of circ_RPPH1 in glioma cell malignancy.

Methods

Human astrocytes (NHA) and glioma cell lines (A172 and U251) were employed in this study. Quantitative real-time polymerase chain reaction and western blot were used to check the expression of circ_RPPH1, microRNA-627-5p (miR-627-5p), miR-663a and syndecan 1 (SDC1). Immunohistochemistry assay was conducted to assess the protein expression of nuclear proliferation marker ki67 and matrix metalloprotein 9 (MMP9). Cell viability was assessed by 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell proliferation and apoptosis were investigated by flow cytometry analysis, 5-Ethynyl-29-deoxyuridine, or cell colony formation assay. Cell migration and invasion were evaluated by transwell assays. The interaction between miRNAs (miR-627-5p and miR-663a) and circ_RPPH1 or SDC1 was identified by a dual-luciferase reporter assay. A mouse model assay was performed to reveal the impact of circ_RPPH1 knockdown on glioma cell malignancy in vivo by analyzing neoplasm volume and weight.

Results

Circ_RPPH1 and SDC1 expression were significantly increased, whereas miR-627-5p and miR-663a expression were decreased in glioma tissues and cells in comparison with healthy brain tissues or human astrocytes. Circ_RPPH1 depletion led to the decreased cell proliferation, migration and invasion, and the increased cell apoptosis. Additionally, circ_RPPH1 bound to miR-627-5p/miR-663a and mediated glioma cell processes by interacting with them. SDC1 overexpression attenuated miR-627-5p/miR-663a-mediated actions. Moreover, circ_RPPH1 regulated SDC1 expression through interaction with miR-627-5p and/or miR-663a. Furthermore, circ_RPPH1 knockdown inhibited glioma cell malignancy in vivo, accompanied by the decreases of ki67 and MMP9 expression.

Conclusion

Circ_RPPH1 knockdown inhibited glioma tumorigenesis by downregulating SDC1 by binding to miR-627-5p/miR-663a, showing that circ_RPPH1 might be an effective therapeutic target for glioma.

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
Fig. 8
Fig. 9

Similar content being viewed by others

Data availability

Not applicable.

References

  • Asuthkar S, Velpula KK, Nalla AK, Gogineni VR, Gondi CS, Rao JS (2014) Irradiation-induced angiogenesis is associated with an MMP-9-miR-494-syndecan-1 regulatory loop in medulloblastoma cells. Oncogene 33(15):1922–1933

    Article  CAS  PubMed  Google Scholar 

  • Bach DH, Lee SK, Sood AK (2019) Circular RNAs in Cancer. Mol Ther Nucleic Acids 16:118–129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bai S, Wu Y, Yan Y, Shao S, Zhang J, Liu J, Hui B, Liu R, Ma H, Zhang X, Ren J (2020) Construct a circRNA/miRNA/mRNA regulatory network to explore potential pathogenesis and therapy options of clear cell renal cell carcinoma. Sci Rep 10(1):13659

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Binder Gallimidi A, Nussbaum G, Hermano E, Weizman B, Meirovitz A, Vlodavsky I, Götte M, Elkin M (2017) Syndecan-1 deficiency promotes tumor growth in a murine model of colitis-induced colon carcinoma. PLoS One 12(3):e0174343

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chen J, Chen T, Zhu Y, Li Y, Zhang Y, Wang Y, Li X, Xie X, Wang J, Huang M, Sun X, Ke Y (2019) circPTN sponges miR-145-5p/miR-330-5p to promote proliferation and stemness in glioma. J Exp Clin Cancer Res 38(1):398

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chen J, Tang J, Chen W, Gao Y, He Y, Zhang Q, Ran Q, Cao F, Yao S (2017) Effects of syndecan-1 on the expression of syntenin and the migration of U251 glioma cells. Oncol Lett 14(6):7217–7224

    PubMed  PubMed Central  Google Scholar 

  • Chi G, Xu D, Zhang B, Yang F (2019) Matrine induces apoptosis and autophagy of glioma cell line U251 by regulation of circRNA-104075/BCL-9. Chem Biol Interact 308:198–205

    Article  CAS  PubMed  Google Scholar 

  • Conn SJ, Pillman KA, Toubia J, Conn VM, Salmanidis M, Phillips CA, Roslan S, Schreiber AW, Gregory PA, Goodall GJ (2015) The RNA binding protein quaking regulates formation of circRNAs. Cell 160(6):1125–1134

    Article  CAS  PubMed  Google Scholar 

  • Dang Y, Wei X, Xue L, Wen F, Gu J, Zheng H (2018) Long Non-Coding RNA in Glioma: Target miRNA and Signaling Pathways. Clin Lab 64(6):887–894

    CAS  PubMed  Google Scholar 

  • Deng Y, Zhu H, Xiao L, Liu C, Meng X (2020) Circ_0005198 enhances temozolomide resistance of glioma cells through miR-198/TRIM14 axis. Aging (albany NY) 13(2):2198–2211

    Article  Google Scholar 

  • Fan Z, Zheng J, Xue Y, Liu X, Wang D, Yang C, Ma J, Liu L, Ruan X, Wang Z, Liu Y (2018) NR2C2-uORF targeting UCA1-miR-627-5p-NR2C2 feedback loop to regulate the malignant behaviors of glioma cells. Cell Death Dis 9(12):1165–1165

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Friedmann-Morvinski D, Narasimamurthy R, Xia Y, Myskiw C, Soda Y, Verma IM (2016) Targeting NF-κB in glioblastoma: A therapeutic approach. Sci Adv 2(1):e1501292

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ge JN, Yan D, Ge CL, Wei MJ (2020) LncRNA C9orf139 can regulate the growth of pancreatic cancer by mediating the miR-663a/Sox12 axis. World J Gastrointest Oncol 12(11):1272–1287

    Article  PubMed  PubMed Central  Google Scholar 

  • Goodenberger ML, Jenkins RB (2012) Genetics of adult glioma. Cancer Genet 205(12):613–621

    Article  CAS  PubMed  Google Scholar 

  • He Z, Ruan X, Liu X, Zheng J, Liu Y, Liu L, Ma J, Shao L, Wang D, Shen S, Yang C, Xue Y (2019) FUS/circ_002136/miR-138-5p/SOX13 feedback loop regulates angiogenesis in Glioma. J Exp Clin Cancer Res 38(1):65

    Article  PubMed  PubMed Central  Google Scholar 

  • Indira Chandran V, Welinder C, Månsson AS, Offer S, Freyhult E, Pernemalm M, Lund SM, Pedersen S, Lehtiö J, Marko-Varga G, Johansson MC, Englund E, Sundgren PC, Belting M (2019) Ultrasensitive Immunoprofiling of Plasma Extracellular Vesicles Identifies Syndecan-1 as a Potential Tool for Minimally Invasive Diagnosis of Glioma. Clin Cancer Res 25(10):3115–3127

    Article  PubMed  Google Scholar 

  • Li J, Liu D, Cui Z (2020) Circ_001680 stimulates glioma progression with the involvement of miR-186-5p. Eur Rev Med Pharmacol Sci 24(11):6211–6218

    CAS  PubMed  Google Scholar 

  • Li Z, Zhang J, Zheng H, Li C, Xiong J, Wang W, Bao H, Jin H, Liang P (2019) Modulating lncRNA SNHG15/CDK6/miR-627 circuit by palbociclib, overcomes temozolomide resistance and reduces M2-polarization of glioma associated microglia in glioblastoma multiforme. Journal of Experimental & Clinical Cancer Research : CR 38(1):380–380

    Article  PubMed Central  CAS  Google Scholar 

  • Liang ZZ, Guo C, Zou MM, Meng P, Zhang TT (2020) circRNA-miRNA-mRNA regulatory network in human lung cancer: an update. Cancer Cell Int 20:173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu Z, Jin H, Yang S, Cao H, Zhang Z, Wen B, Zhou S (2020) SDC1 knockdown induces epithelial-mesenchymal transition and invasion of gallbladder cancer cells via the ERK/Snail pathway. J Int Med Res 48(8):300060520947883

    CAS  PubMed  Google Scholar 

  • Ma Q, Zhang Y, Liang H, Zhang F, Liu F, Chen S, Hu Y, Jiang L, Hao Y, Li M, Liu Y (2018) EMP3, which is regulated by miR-663a, suppresses gallbladder cancer progression via interference with the MAPK/ERK pathway. Cancer Lett 430:97–108

    Article  CAS  PubMed  Google Scholar 

  • Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, Maier L, Mackowiak SD, Gregersen LH, Munschauer M, Loewer A, Ziebold U, Landthaler M, Kocks C, le Noble F, Rajewsky N (2013) Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495(7441):333–338

    Article  CAS  PubMed  Google Scholar 

  • Ostrom QT, Gittleman H, de Blank PM, Finlay JL, Gurney JG, McKean-Cowdin R, Stearns DS, Wolff JE, Liu M, Wolinsky Y, Kruchko C, Barnholtz-Sloan JS (2016) American Brain Tumor Association Adolescent and Young Adult Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2008–2012. Neuro Oncol 181 Supp 1(1):i1–i50

    Article  Google Scholar 

  • Ostrom QT, Gittleman H, Liao P, Rouse C, Chen Y, Dowling J, Wolinsky Y, Kruchko C, Barnholtz-Sloan J (2014) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007–2011. Neuro Oncol 164 Supp 4(Suppl 4):1–63

    Article  Google Scholar 

  • Pan G, Mao A, Liu J, Lu J, Ding J, Liu W (2020) Circular RNA hsa_circ_0061825 (circ-TFF1) contributes to breast cancer progression through targeting miR-326/TFF1 signalling. Cell Prolif 53(2):e12720–e12720

    Article  PubMed  PubMed Central  Google Scholar 

  • Petrescu GED, Sabo AA, Torsin LI, Calin GA, Dragomir MP (2019) MicroRNA based theranostics for brain cancer: basic principles. J Exp Clin Cancer Res 38(1):231

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rajappa A, Banerjee S, Sharma V, Khandelia P (2020) Circular RNAs: Emerging Role in Cancer Diagnostics and Therapeutics. Front Mol Biosci 7:577938–577938

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rong D, Sun H, Li Z, Liu S, Dong C, Fu K, Tang W, Cao H (2017) An emerging function of circRNA-miRNAs-mRNA axis in human diseases. Oncotarget 8(42):73271–73281

    Article  PubMed  PubMed Central  Google Scholar 

  • Sayyad MR, Puchalapalli M, Vergara NG, Wangensteen SM, Moore M, Mu L, Edwards C, Anderson A, Kall S, Sullivan M, Dozmorov M, Singh J, Idowu MO, Koblinski JE (2019) Syndecan-1 facilitates breast cancer metastasis to the brain. Breast Cancer Res Treat 178(1):35–49

    Article  CAS  PubMed  Google Scholar 

  • Shi F, Shi Z, Zhao Y, Tian J (2019) CircRNA hsa-circ-0014359 promotes glioma progression by regulating miR-153/PI3K signaling. Biochem Biophys Res Commun 510(4):614–620

    Article  CAS  PubMed  Google Scholar 

  • Shi S, Zhong D, Xiao Y, Wang B, Wang W, Zhang F, Huang H (2017) Syndecan-1 knockdown inhibits glioma cell proliferation and invasion by deregulating a c-src/FAK-associated signaling pathway. Oncotarget 8(25):40922–40934

    Article  PubMed  PubMed Central  Google Scholar 

  • Sun F, Wu K, Yao Z, Mu X, Zheng Z, Sun M, Wang Y, Liu Z, Zhu Y (2020) Long Noncoding RNA PVT1 Promotes Prostate Cancer Metastasis by Increasing NOP2 Expression via Targeting Tumor Suppressor MicroRNAs. Onco Targets Ther 13:6755–6765

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun J, Li B, Shu C, Ma Q, Wang J (2020) Functions and clinical significance of circular RNAs in glioma. Mol Cancer 19(1):34–34

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang J, Chen T, Wang L, Yao B, Sun L, Chen S, Liu Q (2020) MicroRNA-627-5p inhibits the proliferation of hepatocellular carcinoma cells by targeting BCL3 transcription coactivator. Clin Exp Pharmacol Physiol 47(3):485–494

    Article  PubMed  CAS  Google Scholar 

  • Wang L, Wu H, Chu F, Zhang L, Xiao X (2020) Knockdown of circ_0000512 Inhibits Cell Proliferation and Promotes Apoptosis in Colorectal Cancer by Regulating miR-296-5p/RUNX1 Axis. Onco Targets Ther 13:7357–7368

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang W, Zhang A, Hao Y, Wang G, Jia Z (2018) The emerging role of miR-19 in glioma. J Cell Mol Med 22(10):4611–4616

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang X, Feng H, Dong W, Wang F, Zhang G, Wu J (2020) Hsa_circ_0008225 inhibits tumorigenesis of glioma via sponging miR-890 and promoting ZMYND11 expression. J Pharmacol Sci 143(2):74–82

    Article  CAS  PubMed  Google Scholar 

  • Xiong DD, Dang YW, Lin P, Wen DY, He RQ, Luo DZ, Feng ZB, Chen G (2018) A circRNA-miRNA-mRNA network identification for exploring underlying pathogenesis and therapy strategy of hepatocellular carcinoma. J Transl Med 16(1):220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yuan SX, Li JL, Xu XK, Chen W, Chen C, Kuang KQ, Wang FY, Wang K, Li FC (2018) Underlying mechanism of the photodynamic activity of hematoporphyrin-induced apoptosis in U87 glioma cells. Int J Mol Med 41(4):2288–2296

    CAS  PubMed  Google Scholar 

  • Zhang C, Chen B, Jiao A, Li F, Sun N, Zhang G, Zhang J (2018) miR-663a inhibits tumor growth and invasion by regulating TGF-β1 in hepatocellular carcinoma. BMC Cancer 18(1):1179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Z, Yang T, Xiao J (2018) Circular RNAs: Promising Biomarkers for Human Diseases. EBioMedicine 34:267–274

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhao G, Dai GJ (2020) Hsa_circRNA_000166 Promotes Cell Proliferation, Migration and Invasion by Regulating miR-330-5p/ELK1 in Colon Cancer. Onco Targets Ther 13:5529–5539

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao S, Xiong W, Xu K (2020) MiR-663a, regulated by lncRNA GAS5, contributes to osteosarcoma development through targeting MYL9. Hum Exp Toxicol 39(12):1607–1618

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurosurgery, The First Affiliated Hospital of Xi’an Jiao-Tong University, No.227, Yanta west Road, Xi’an, 710061, Shaanxi province, China

    Wei Chen, Xiao Yu, Ning Wang, Jiangpeng Jing, Ruichun Li & Minxue Lian

  2. Xi’an, China

    Minxue Lian

Authors
  1. Wei Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiao Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ning Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jiangpeng Jing
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ruichun Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Minxue Lian
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Minxue Lian.

Ethics declarations

Ethics approval and consent to participate

Written informed consents were obtained from all participants and this study was permitted by the Ethics Committee of The first affiliated hospital of xi’an jiao-tong university.

Consent for publication

Not applicable.

Disclosure of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, W., Yu, X., Wang, N. et al. Circ_RPPH1 regulates glioma cell malignancy by binding to miR-627-5p/miR-663a to induce SDC1 expression. Metab Brain Dis 37, 1231–1245 (2022). https://doi.org/10.1007/s11011-022-00965-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-022-00965-y

Keywords

Search

Navigation