Skip to main content
SpringerLink
Log in

Hsa_circ_0052611 and mir-767-5p guide the warburg effect, migration, and invasion of BRCA cells through modulating SCAI

  • Published:
Journal of Bioenergetics and Biomembranes Aims and scope Submit manuscript

Abstract

Noncoding RNAs are key regulators in the Warburg Effect, an emerging hallmark of cancer. We intended to investigate the role and mechanism of circular RNA hsa_circ_0052611 (circ_0052611) and microRNA (miR)-767-5p in breast cancer (BRCA) hallmarks, especially the Warburg Effect. Expression of circ_0052611 and SCAI was downregulated, and miR-767-5p was upregulated in human BRCA tissues and cells; moreover, circ_0052611 acted as a miR-767-5p sponge to modulate the expression of miR-767-5p-targeted SCAI. Functionally, re-expressing circ_0052611 suppressed migration, invasion, glucose uptake, lactate production, and extracellular acidification rate (ECAR) in BRCA cells, and promoted apoptotic rate. These effects were accompanied by decreased Vimentin, N-cadherin, Bcl-2, and LDHA, and increased E-cadherin and Bax. Consistently, exhausting miR-767-5p exerted similar effects in BRCA cells. High miR-767-5p could counteract the role of circ_0052611 overexpression, and low SCAI likewise blocked the role of miR-767-5p deletion. In vivo, upregulating circ_0052611 delayed tumor growth of BRCA cells by altering miR-767-5p and SCAI expression. circ_0052611/miR-767-5p/SCAI axis might boycott the malignancy of BRCA cells.

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

Similar content being viewed by others

Data Availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

References

  • Abdollahzadeh R, Daraei A, Mansoori Y, Sepahvand M, Amoli MM, Tavakkoly-Bazzaz J (2019) Competing endogenous RNA (ceRNA) cross talk and language in ceRNA regulatory networks: a new look at hallmarks of breast cancer. J Cell Physiol 234(7):10080–10100

    Article  CAS  PubMed  Google Scholar 

  • Bammert L, Jonas S, Ungricht R, Kutay U (2016) Human AATF/Che-1 forms a nucleolar protein complex with NGDN and NOL10 required for 40S ribosomal subunit synthesis. Nucleic Acids Res 44(20):9803–9820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bandyopadhyay S, Bluth MH, Ali-Fehmi R (2018) Breast carcinoma: updates in Molecular Profiling 2018. Clin Lab Med 38(2):401–420

    Article  PubMed  Google Scholar 

  • Brandt DT, Baarlink C, Kitzing TM, Kremmer E, Ivaska J, Nollau P et al (2009) SCAI acts as a suppressor of cancer cell invasion through the transcriptional control of beta1-integrin. Nat Cell Biol 11(5):557–568

    Article  CAS  PubMed  Google Scholar 

  • Cadoo KA, Traina TA, King TA (2013) Advances in molecular and clinical subtyping of breast cancer and their implications for therapy. Surg Oncol Clin N Am 22(4):823–840

    Article  PubMed  Google Scholar 

  • Cairns RA (2015) Drivers of the Warburg phenotype. Cancer J 21(2):56–61

    Article  CAS  PubMed  Google Scholar 

  • Chen X, Hu W, Xie B, Gao H, Xu C, Chen J (2014) Downregulation of SCAI enhances glioma cell invasion and stem cell like phenotype by activating Wnt/beta-catenin signaling. Biochem Biophys Res Commun 448(2):206–211

    Article  CAS  PubMed  Google Scholar 

  • Di Leva G, Garofalo M, Croce CM (2014) MicroRNAs in cancer. Annu Rev Pathol 9:287–314

    Article  PubMed  Google Scholar 

  • Du Y, Wei N, Ma R, Jiang S, Song D (2020) A mir-210-3p regulon that controls the Warburg effect by modulating HIF-1alpha and p53 activity in triple-negative breast cancer. Cell Death Dis 11(9):731

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feng W, Gentles A, Nair RV, Huang M, Lin Y, Lee CY et al (2014) Targeting unique metabolic properties of breast tumor initiating cells. Stem Cells 32(7):1734–1745

    Article  CAS  PubMed  Google Scholar 

  • Gasparics A, Kokeny G, Fintha A, Bencs R, Mozes MM, Agoston EI et al (2018) Alterations in SCAI expression during cell plasticity, fibrosis and Cancer. Pathol Oncol Res 24(3):641–651

    Article  CAS  PubMed  Google Scholar 

  • Geng H, Li K, Pan Q, Tao S, Li C, Zhao H et al (2020) Identification and expression of several circular RNAs and knockdown of hsa_circ_0005556 exerts oncogenic functions by mir-767-5p in gastric Cancer. Med Sci Monit 26:e921163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hu X, Bao M, Huang J, Zhou L, Zheng S (2020) Identification and validation of novel biomarkers for diagnosis and prognosis of Hepatocellular Carcinoma. Front Oncol 10:541479

    Article  PubMed  PubMed Central  Google Scholar 

  • Icard P, Shulman S, Farhat D, Steyaert JM, Alifano M, Lincet H (2018) How the Warburg effect supports aggressiveness and drug resistance of cancer cells? Drug Resist Updat 38:1–11

    Article  PubMed  Google Scholar 

  • Jia M, Li Z, Pan M, Tao M, Wang J, Lu X (2020) LINC-PINT suppresses the aggressiveness of thyroid Cancer by downregulating mir-767-5p to Induce TET2 expression. Mol Ther Nucleic Acids 22:319–328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Keating E, Martel F (2018) Antimetabolic Effects of polyphenols in breast Cancer cells: focus on glucose uptake and metabolism. Front Nutr 5:25

    Article  PubMed  PubMed Central  Google Scholar 

  • Li M, He XY, Zhang ZM, Li S, Ren LH, Cao RS et al (2015) MicroRNA-1290 promotes esophageal squamous cell carcinoma cell proliferation and metastasis. World J Gastroenterol 21(11):3245–3255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Z, Chen Z, Hu G, Jiang Y (2019) Roles of circular RNA in breast cancer: present and future. Am J Transl Res 11(7):3945–3954

    CAS  PubMed  PubMed Central  Google Scholar 

  • Li X, Xu M, Lv W, Yang X (2020) Ultrasound-targeted microbubble destruction-mediated miR-767 inhibition suppresses tumor progression of non-small cell lung cancer. Exp Ther Med 19(5):3391–3397

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lin L, Liu D, Liang H, Xue L, Su C, Liu M (2015) MiR-1228 promotes breast cancer cell growth and metastasis through targeting SCAI protein. Int J Clin Exp Pathol 8(6):6646–6655

    PubMed  PubMed Central  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25(4):402–408

    Article  CAS  PubMed  Google Scholar 

  • Lu HF, Yuan WP, Li M, Huang Q, Liu JP, Li LQ et al (2015) Properly assessing CD133 as a risk factor for poor prognosis in patients with hepatocellular carcinoma after resection. Tumour Biol 36(7):4937–4938

    Article  PubMed  Google Scholar 

  • Macharia LW, Wanjiru CM, Mureithi MW, Pereira CM, Ferrer VP, Moura-Neto V (2019) MicroRNAs, Hypoxia and the Stem-Like State as Contributors to Cancer aggressiveness. Front Genet 10:125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mirzaei H, Hamblin MR (2020) Regulation of glycolysis by non-coding RNAs in Cancer: switching on the Warburg Effect. Mol Ther Oncolytics 19:218–239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Misir S, Hepokur C, Aliyazicioglu Y, Enguita FJ (2020) Circular RNAs serve as miRNA sponges in breast cancer. Breast Cancer 27(6):1048–1057

    Article  PubMed  Google Scholar 

  • Nan A, Chen L, Zhang N, Jia Y, Li X, Zhou H et al (2019) Circular RNA circNOL10 inhibits Lung Cancer Development by promoting SCLM1-Mediated transcriptional regulation of the humanin polypeptide family. Adv Sci (Weinh) 6(2):1800654

    Article  PubMed  Google Scholar 

  • Ou ZL, Luo Z, Wei W, Liang S, Gao TL, Lu YB (2019) Hypoxia-induced shedding of MICA and HIF1A-mediated immune escape of pancreatic cancer cells from NK cells: role of circ_0000977/miR-153 axis. RNA Biol 16(11):1592–1603

    Article  PubMed  PubMed Central  Google Scholar 

  • Panda AC (2018) Circular RNAs act as miRNA sponges. Adv Exp Med Biol 1087:67–79

    Article  CAS  PubMed  Google Scholar 

  • Pardini B, Sabo AA, Birolo G, Calin GA (2019) Noncoding RNAs in Extracellular Fluids as Cancer biomarkers: the New Frontier of Liquid Biopsies. Cancers (Basel) 11(8):1170

    Article  CAS  PubMed  Google Scholar 

  • Percie du Sert N, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M et al (2020) The ARRIVE guidelines 2.0: updated guidelines for reporting animal research. PLoS Biol 18(7):e3000410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pinweha P, Rattanapornsompong K, Charoensawan V, Jitrapakdee S (2016) MicroRNAs and oncogenic transcriptional regulatory networks controlling metabolic reprogramming in cancers. Comput Struct Biotechnol J 14:223–233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Plaisier CL, Pan M, Baliga NS (2012) A miRNA-regulatory network explains how dysregulated miRNAs perturb oncogenic processes across diverse cancers. Genome Res 22(11):2302–2314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rui T, Xu S, Feng S, Zhang X, Huang H, Ling Q (2020) The mir-767-105 cluster: a crucial factor related to the poor prognosis of hepatocellular carcinoma. Biomark Res 8:7

    Article  PubMed  PubMed Central  Google Scholar 

  • Samec M, Liskova A, Koklesova L, Samuel SM, Zhai K, Buhrmann C et al (2020) Flavonoids against the Warburg phenotype-concepts of predictive, preventive and personalised medicine to cut the Gordian knot of cancer cell metabolism. EPMA J 11(3):377–398

    Article  PubMed  PubMed Central  Google Scholar 

  • Shankaraiah RC, Veronese A, Sabbioni S, Negrini M (2018) Non-coding RNAs in the reprogramming of glucose metabolism in cancer. Cancer Lett 419:167–174

    Article  CAS  PubMed  Google Scholar 

  • Singh SK, Singh S, Lillard JW Jr., Singh R (2017) Drug delivery approaches for breast cancer. Int J Nanomedicine 12:6205–6218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tran AM, Chalbatani GM, Berland L, Cruz De Los Santos M, Raj P, Jalali SA et al (2020) A New World of biomarkers and therapeutics for female Reproductive system and breast cancers: circular RNAs. Front Cell Dev Biol 8:50

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang Z, Jiang Q, Dong C (2020) Metabolic reprogramming in triple-negative breast cancer. Cancer Biol Med 17(1):44–59

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang F, Wang X, Li J, Lv P, Han M, Li L et al (2021) CircNOL10 suppresses breast cancer progression by sponging mir-767-5p to regulate SOCS2/JAK/STAT signaling. J Biomed Sci 28(1):4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu Z, Wu J, Zhao Q, Fu S, Jin J (2020) Emerging roles of aerobic glycolysis in breast cancer. Clin Transl Oncol 22(5):631–646

    Article  CAS  PubMed  Google Scholar 

  • Xia M, Feng S, Chen Z, Wen G, Zu X, Zhong J (2020) Non-coding RNAs: key regulators of aerobic glycolysis in breast cancer. Life Sci 250:117579

    Article  CAS  PubMed  Google Scholar 

  • Xu D, Gu M, Liu HL (2019) MicroRNA-625-3p promotes cell migration of oral squamous cell carcinoma by regulating SCAI expression. Eur Rev Med Pharmacol Sci 23(2):641–648

    CAS  PubMed  Google Scholar 

  • Yi T, Zhou X, Sang K, Zhou J, Ge L (2019) MicroRNA-1270 modulates papillary thyroid cancer cell development by regulating SCAI. Biomed Pharmacother 109:2357–2364

    Article  CAS  PubMed  Google Scholar 

  • Yizhak K, Le Devedec SE, Rogkoti VM, Baenke F, de Boer VC, Frezza C et al (2014) A computational study of the Warburg effect identifies metabolic targets inhibiting cancer migration. Mol Syst Biol 10:744

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Tang K, Chen L, Du M, Qu Z (2020a) Exosomal CircGDI2 suppresses oral squamous cell carcinoma progression through the regulation of MiR-424-5p/SCAI Axis. Cancer Manag Res 12:7501–7514

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Zhang Z, Yi Y, Wang Y, Fu J (2020b) CircNOL10 Acts as a sponge of miR-135a/b-5p in suppressing Colorectal Cancer Progression via regulating KLF9. Onco Targets Ther 13:5165–5176

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Qian K, Liu X, Zhao X, Zhao T, Lu G (2022) Exosomal mir-625-3p derived from hypoxic lung cancer cells facilitates metastasis by targeting SCAI. Mol Biol Rep 49(10):9275–9281

    Article  CAS  PubMed  Google Scholar 

  • Zhou SY, Chen W, Yang SJ, Xu ZH, Hu JH, Zhang HD et al (2019) The emerging role of circular RNAs in breast cancer. Biosci Rep 39(6):BSR20190621

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zubor P, Kubatka P, Dankova Z, Gondova A, Kajo K, Hatok J et al (2018) miRNA in a multiomic context for diagnosis, treatment monitoring and personalized management of metastatic breast cancer. Future Oncol 14(18):1847–1867

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

None.

Funding

This study was supported by

1. The Joint construction project of Medical science and technology in Henan Province, Grant/Award Number: LHGJ20220489.

2. The Joint construction proect of Medica sciece and technology in Henan Province, Grant Award Number: LHGJ20220487.

3. Henan Medical Education Research Project, Grant Award Number:Wjlx2022072.

Author information

Author notes

  1. Xin Wang and Zongwen Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Radiation Oncology, The Second Affiliated Hospital of Zhengzhou University, No.2, Jingba Road, Jinshui District, Zhengzhou, 450014, China

    Xin Wang, Zongwen Liu, Alan Chu, Rui Song, Shijia Liu, Ting Chai & Chen Sun

Authors
  1. Xin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zongwen Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alan Chu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rui Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shijia Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ting Chai
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chen Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conception and design of experiments: Xin Wang and Zongwen Liu; Experimental part and interpretation of data: Zongwen Liu, Alan Chu and Rui Song; Data analysis and statistics: Rui Song and Shijia Liu; Project administration: Xin Wang; Writing – original draft: Xin Wang, Zongwen Liu; Writing - review and editing: Ting Chai and Chen Sun. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Chen Sun.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the Ethics Committee of the Second Affiliated Hospital of Zhengzhou University. Animal studies were granted by the Animal Experiment Administration Committee of the Second Affiliated Hospital of Zhengzhou University.

Consent to participate

Not applicable.

Competing interests

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.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

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, X., Liu, Z., Chu, A. et al. Hsa_circ_0052611 and mir-767-5p guide the warburg effect, migration, and invasion of BRCA cells through modulating SCAI. J Bioenerg Biomembr 55, 381–396 (2023). https://doi.org/10.1007/s10863-023-09985-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10863-023-09985-4

Keywords

Search

Navigation