Skip to main content
SpringerLink
Log in

CircPLK1 Acts as a Carcinogenic Driver to Promote the Development of Malignant Pleural Mesothelioma by Governing the miR-1294/HMGA1 Pathway

  • Original Article
  • Published:
Biochemical Genetics Aims and scope Submit manuscript

Abstract

The deregulation of circular RNAs (circRNAs) is involved in cancer development. CircRNA polo-like kinase 1 (circPLK1) was reported to promote breast cancer development. However, the role of circPLK1 in malignant pleural mesothelioma (MPM) is unclear. The expression of circPLK1, miR-1294, and high mobility group AT-hook 1 (HMGA1) mRNA was measured by quantitative real-time PCR (qPCR). Cell viability was detected by CCK-8 assay. Colony formation ability was monitored by colony formation assay. Cell proliferation was detected by EdU assay. Cell migration and cell invasion were monitored by transwell assay. Cancer cell stemness was investigated by sphere formation assay. The protein levels of marker proteins and HMGA1 expression were measured by western blot analysis. The binding relationship between miR-1294 and circPLK1 or HMGA1 was validated by pull-down assay, dual-luciferase reporter assay or RIP assy. Animal study was performed to disclose the role of circPLK1 in vivo. Exosomes were identified by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). CircPLK1 was upregulated in MPM tumor tissues and cell lines. CircPLK1 knockdown suppressed the proliferation, migration, invasion and stemness of MPM cells. CircPLK1 contained a binding site for miR-1294 and thus bound to miR-1294 to sequester its expression. Inhibition of miR-1294 reversed the effects of circPLK1 knockdown. HMGA1 was a target of miR-1294, and circPLK1 bound to miR-1294 to increase the expression of HMGA1. MiR-1294 restoration also suppressed the proliferation, migration, invasion and stemness of MPM cells, while these effects were abolished by HMGA1 overexpression. In addition, circPLK1 knockdown inhibited tumor growth in vivo. CircPLK1 was overexpressed in exosomes derived from serum of MPM patients. CircPLK1 knockdown inhibited MPM cell proliferation, migration, invasion and stemness by targeting the miR-1294/HMGA1 pathway.

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

  • Baas P, Fennell D, Kerr KM, Van Schil PE, Haas RL, Peters S et al (2015) Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 26(Suppl 5):v31-39

    Article  Google Scholar 

  • Beckett P, Edwards J, Fennell D, Hubbard R, Woolhouse I, Peake MD (2015) Demographics, management and survival of patients with malignant pleural mesothelioma in the National Lung Cancer Audit in England and Wales. Lung Cancer 88(3):344–348

    Article  CAS  Google Scholar 

  • Belousova EA, Filipenko ML, Kushlinskii NE (2018) Circular RNA: new regulatory molecules. Bull Exp Biol Med 164(6):803–815

    Article  CAS  Google Scholar 

  • Cao XP, Cao Y, Zhao H, Yin J, Hou P (2019) HMGA1 promoting gastric cancer oncogenic and glycolytic phenotypes by regulating c-myc expression. Biochem Biophys Res Commun 516(2):457–465

    Article  CAS  Google Scholar 

  • Chang ZG, Yang LY, Wang W, Peng JX, Huang GW, Tao YM et al (2005) Determination of high mobility group A1 (HMGA1) expression in hepatocellular carcinoma: a potential prognostic marker. Dig Dis Sci 50(10):1764–1770

    Article  CAS  Google Scholar 

  • Chen H, Liu L, Li X, Shi Y, Liu N (2018) MicroRNA-1294 inhibits the proliferation and enhances the chemosensitivity of glioma to temozolomide via the direct targeting of TPX2. Am J Cancer Res 8(2):291–301

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen M, Xu K, Li B, Wang N, Zhang Q, Chen L et al (2020) HMGA1 Regulates the stem cell-like properties of circulating tumor cells from GIST patients via Wnt/beta-catenin pathway. Onco Targets Ther 13:4943–4956

    Article  CAS  Google Scholar 

  • Cinausero M, Rihawi K, Cortiula F, Follador A, Fasola G, Ardizzoni A (2019) Emerging therapies in malignant pleural mesothelioma. Crit Rev Oncol Hematol 144:102815

    Article  Google Scholar 

  • Fu F, Wang T, Wu Z, Feng Y, Wang W, Zhou S et al (2018) HMGA1 exacerbates tumor growth through regulating the cell cycle and accelerates migration/invasion via targeting miR-221/222 in cervical cancer. Cell Death Dis 9(6):594

    Article  Google Scholar 

  • Ismail-Khan R, Robinson LA, Williams CC Jr, Garrett CR, Bepler G, Simon GR (2006) Malignant pleural mesothelioma: a comprehensive review. Cancer Control 13(4):255–263

    Article  Google Scholar 

  • Johnson TG, Schelch K, Cheng YY, Williams M, Sarun KH, Kirschner MB et al (2018) Dysregulated expression of the microRNA miR-137 and its target YBX1 contribute to the invasive characteristics of malignant pleural mesothelioma. J Thorac Oncol 13(2):258–272

    Article  CAS  Google Scholar 

  • Kan XQ, Li YB, He B, Cheng S, Wei Y, Sun J (2020) MiR-1294 acts as a tumor inhibitor in cervical cancer by regulating FLOT1 expression. J Biol Regul Homeost Agents. https://doi.org/10.23812/20-10A

    Article  PubMed  Google Scholar 

  • Khodayari N, Mohammed KA, Lee H, Kaye F, Nasreen N (2016) MicroRNA-302b targets Mcl-1 and inhibits cell proliferation and induces apoptosis in malignant pleural mesothelioma cells. Am J Cancer Res 6(9):1996–2009

    CAS  PubMed  PubMed Central  Google Scholar 

  • Klonisch T, Wiechec E, Hombach-Klonisch S, Ande SR, Wesselborg S, Schulze-Osthoff K et al (2008) Cancer stem cell markers in common cancers - therapeutic implications. Trends Mol Med 14(10):450–460

    Article  CAS  Google Scholar 

  • Kong Y, Yang L, Wei W, Lyu N, Zou Y, Gao G et al (2019) CircPLK1 sponges miR-296-5p to facilitate triple-negative breast cancer progression. Epigenomics 11(10):1163–1176

    Article  CAS  Google Scholar 

  • Lin G, Wang S, Zhang X, Wang D (2020) Circular RNA circPLK1 promotes breast cancer cell proliferation, migration and invasion by regulating miR-4500/IGF1 axis. Cancer Cell Int 20(1):593

    Article  CAS  Google Scholar 

  • Liu K, Li L, Rusidanmu A, Wang Y, Lv X (2015) Down-regulation of MiR-1294 is related to dismal prognosis of patients with esophageal squamous cell carcinoma through elevating C-MYC expression. Cell Physiol Biochem 36(1):100–110

    Article  Google Scholar 

  • Renganathan A, Kresoja-Rakic J, Echeverry N, Ziltener G, Vrugt B, Opitz I et al (2014) GAS5 long non-coding RNA in malignant pleural mesothelioma. Mol Cancer 13:119

    Article  Google Scholar 

  • Robb T, Reid G, Blenkiron C (2017) Exploiting microRNAs as cancer therapeutics. Target Oncol 12(2):163–178

    Article  Google Scholar 

  • Wang M, Yu F, Wu W, Zhang Y, Chang W, Ponnusamy M et al (2017) Circular RNAs: a novel type of non-coding RNA and their potential implications in antiviral immunity. Int J Biol Sci 13(12):1497–1506

    Article  CAS  Google Scholar 

  • Xu T, Wu J, Han P, Zhao Z, Song X (2017) Circular RNA expression profiles and features in human tissues: a study using RNA-seq data. BMC Genom 18(Suppl 6):680

    Article  Google Scholar 

  • Yuan Q, Yu H, Chen J, Song X, Sun L (2020) Antitumor effect of miR-1294/pyruvate kinase M2 signaling cascade in osteosarcoma cells. Onco Targets Ther 13:1637–1647

    Article  CAS  Google Scholar 

  • Zalcman G, Mazieres J, Margery J, Greillier L, Audigier-Valette C, Moro-Sibilot D et al (2016) Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet 387(10026):1405–1414

    Article  CAS  Google Scholar 

  • Zanin R, Pegoraro S, Ros G, Ciani Y, Piazza S, Bossi F et al (2019) HMGA1 promotes breast cancer angiogenesis supporting the stability, nuclear localization and transcriptional activity of FOXM1. J Exp Clin Cancer Res 38(1):313

    Article  Google Scholar 

Download references

Funding

This study was supported by Chongqing Science and Health Joint Medical Research Project (NO. 2021MSXM214).

Author information

Authors and Affiliations

  1. Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, No. 181, Hanyu Road, Shapingba District, Chongqing, 400030, China

    Qi Zhang, Zhiqiang Wang, Huarong Cai, Dongming Guo, Wei Xu, Shi Bu & Yuequan Jiang

Authors
  1. Qi Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhiqiang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Huarong Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dongming Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wei Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shi Bu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yuequan Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

YJ designed and supervised the study. QZ and ZW conducted the experiments and drafted the manuscript. HC and DG collected and analyzed the data. WX and SB contributed the methodology and edited the manuscript.

Corresponding author

Correspondence to Yuequan Jiang.

Ethics declarations

Conflict 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.

Supplementary Information

Below is the link to the electronic supplementary material.

10528_2022_10186_MOESM1_ESM.tif

Fig. S1 CircPLK1 knockdown arrested cancer cell cycle arrest. (A and B) The effect of si-circPLK1#1 on cell cycle was determined by flow cytometry assay. **P<0.01. Supplementary file1 (TIF 1045 KB).

10528_2022_10186_MOESM2_ESM.tif

Fig. S2 The screening of HMGA1 from the target genes of miR-1294. (A and B) The expression of several genes potentially targeted by miR-1294 in MSTO-211H and H2052 cells after miR-1294 overexpression was checked by qPCR. ***P<0.001. Supplementary file2 (TIF 248 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, Q., Wang, Z., Cai, H. et al. CircPLK1 Acts as a Carcinogenic Driver to Promote the Development of Malignant Pleural Mesothelioma by Governing the miR-1294/HMGA1 Pathway. Biochem Genet 60, 1527–1546 (2022). https://doi.org/10.1007/s10528-022-10186-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10528-022-10186-8

Keywords

Search

Navigation