Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Cancer Cell International
Published in: Cancer Cell International 1/2020

01-12-2020 | Glioma | Primary research

Circular RNA circPITX1 knockdown inhibits glycolysis to enhance radiosensitivity of glioma cells by miR-329-3p/NEK2 axis

Authors: Yongchang Guan, Zhi Cao, Jinghua Du, Tao Liu, Tingzhong Wang

Published in: Cancer Cell International | Issue 1/2020

Login to get access

Abstract

Background

Numerous circular RNAs (circRNAs) have been recognized as vital modulators of human malignancies, including glioma. Whereas, the functional role of circRNA Pituitary Homeo Box 1 (circPITX1) in the radioresistance of glioma cells remains largely uncertain.

Methods

Quantitative real-time PCR (qRT-PCR) or western blot analysis was employed to examine the expression of circPITX1, microRNA (miR)-329-3p and NIMA-related kinase 2 (NEK2). 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay was used to determine cell viability. Glycolysis was assessed by commercial kits and western blot analysis. Colony formation assay was conducted to analyze cell survival and clonogenicity capacity. The relationship among circPITX1, miR-329-3p and NEK2 was confirmed via dual-luciferase reporter assay. The in vivo function of circPITX1 was evaluated by tumor xenograft assay.

Results

Expression of circPITX1 and NEK2 was up-regulated in glioma tissues and cells, while miR-329-3p exhibited reverse trend. CircPITX1 knockdown repressed viability, glycolysis and colony formation, but promoted radiosensitivity of glioma cells, as well as inhibited tumor growth in vivo. MiR-329-3p was a target miRNA of circPITX1 and miR-329-3p deficiency reversed knockdown of circPITX1-mediated glycolysis inhibition and radioresistance reduction. MiR-329-3p exerted inhibitory effects on glycolysis and radioresistance of glioma cells by targeting NEK2. CircPITX1 facilitated NEK2 expression by sponging miR-329-3p. Glycolytic inhibitor 2-deoxy-d-glucose (2-DG) disposition weakened the promoted impact on glycolysis caused by circPITX1.

Conclusion

CircPITX1 knockdown reduced glycolysis to contribute to radiosensitivity in glioma through miR-329-3p/NEK2 axis, providing a possible mechanism of circPITX1 in the development of glioma.
Literature
1.
Ricard D, Idbaih A, Ducray F, Lahutte M, Hoang-Xuan K, Delattre JY. Primary brain tumours in adults. Lancet (London, England). 2012;379(9830):1984–96.CrossRef
2.
Zhao J, Liu P, Ma J, Li D, Yang H, Chen W, Jiang Y. Enhancement of radiosensitization by silver nanoparticles functionalized with polyethylene glycol and aptamer As1411 for glioma irradiation therapy. Int J Nanomed. 2019;14:9483–96.CrossRef
3.
Epstein T, Gatenby RA, Brown JS. The Warburg effect as an adaptation of cancer cells to rapid fluctuations in energy demand. PLoS ONE. 2017;12(9):e0185085.CrossRef
4.
Ganapathy-Kanniappan S, Geschwind JF. Tumor glycolysis as a target for cancer therapy: progress and prospects. Mol Cancer. 2013;12:152.CrossRef
5.
Dong L, He Y, Zhou S, Cao Y, Li Y, Bi Y, Liu G. HIF1alpha-dependent metabolic signals control the differentiation of follicular helper T cells. Cells. 2019;8(11):1450.CrossRef
6.
Kudryavtseva AV, Fedorova MS, Zhavoronkov A, Moskalev AA, Zasedatelev AS, Dmitriev AA, Sadritdinova AF, Karpova IY, Nyushko KM, Kalinin DV, et al. Effect of lentivirus-mediated shRNA inactivation of HK1, HK2, and HK3 genes in colorectal cancer and melanoma cells. BMC Genet. 2016;17(Suppl 3):156.CrossRef
7.
Hou XM, Yuan SQ, Zhao D, Liu XJ, Wu XA. LDH-A promotes malignant behavior via activation of epithelial-to-mesenchymal transition in lung adenocarcinoma. Biosci Rep. 2019;39(1):BSR20181476.CrossRef
8.
Shen H, Hau E, Joshi S, Dilda PJ, McDonald KL. Sensitization of glioblastoma cells to irradiation by modulating the glucose metabolism. Mol Cancer Ther. 2015;14(8):1794–804.CrossRef
9.
Huang G, Li S, Yang N, Zou Y, Zheng D, Xiao T. Recent progress in circular RNAs in human cancers. Cancer Lett. 2017;404:8–18.CrossRef
10.
Shang Q, Yang Z, Jia R, Ge S. The novel roles of circRNAs in human cancer. Mol Cancer. 2019;18(1):6.CrossRef
11.
Jin P, Huang Y, Zhu P, Zou Y, Shao T, Wang O. CircRNA circHIPK3 serves as a prognostic marker to promote glioma progression by regulating miR-654/IGF2BP3 signaling. Biochem Biophys Res Commun. 2018;503(3):1570–4.CrossRef
12.
Shi F, Shi Z, Zhao Y, Tian J. CircRNA hsa-circ-0014359 promotes glioma progression by regulating miR-153/PI3K signaling. Biochem Biophys Res Commun. 2019;510(4):614–20.CrossRef
13.
Peng H, Qin C. circCPA4 acts as a prognostic factor and regulates the proliferation and metastasis of glioma. J Cell Mol Med. 2019;23(10):6658–65.CrossRef
14.
Wang R, Zhang S, Chen X, Li N, Li J, Jia R, Pan Y, Liang H. EIF4A3-induced circular RNA MMP9 (circMMP9) acts as a sponge of miR-124 and promotes glioblastoma multiforme cell tumorigenesis. Mol Cancer. 2018;17(1):166.CrossRef
15.
Chen M, Liu X, Xie P, Wang P, Liu M, Zhan Y, Wang H, Feng Y, Li Y. Circular RNA circ_0074026 indicates unfavorable prognosis for patients with glioma and facilitates oncogenesis of tumor cells by targeting miR-1304 to modulate ERBB4 expression. J Cell Physiol. 2019;235(5):4688–97.CrossRef
16.
Wang S, Yin Y, Liu S. Roles of microRNAs during glioma tumorigenesis and progression. Histol Histopathol. 2019;34(3):213–22.PubMed
17.
Zhang Y, Chen J. Prognostic significance of MicroRNAs in glioma: a systematic review and meta-analysis. Biomed Res Int. 2019;2019:4015969.PubMedPubMedCentral
18.
Chang YH, Yin F, Fan GF, Zhao M. Down-regulation of miR-329-3p is associated with worse prognosis in patients with cervical cancer. Eur Rev Med Pharmacol Sci. 2017;21(18):4045–9.PubMed
19.
Qiu S, Lin S, Hu D, Feng Y, Tan Y, Peng Y. Interactions of miR-323/miR-326/miR-329 and miR-130a/miR-155/miR-210 as prognostic indicators for clinical outcome of glioblastoma patients. J Transl Med. 2013;11:10.CrossRef
20.
Hayward DG, Fry AM. Nek2 kinase in chromosome instability and cancer. Cancer Lett. 2006;237(2):155–66.CrossRef
21.
Zeng YR, Han ZD, Wang C, Cai C, Huang YQ, Luo HW, Liu ZZ, Zhuo YJ, Dai QS, Zhao HB, et al. Overexpression of NIMA-related kinase 2 is associated with progression and poor prognosis of prostate cancer. BMC Urol. 2015;15:90.CrossRef
22.
Liu H, Liu B, Hou X, Pang B, Guo P, Jiang W, Ding Q, Zhang R, Xin T, Guo H, et al. Overexpression of NIMA-related kinase 2 is associated with poor prognoses in malignant glioma. J Neurooncol. 2017;132(3):409–17.CrossRef
23.
Koch A, Ebert EV, Seitz T, Dietrich P, Berneburg M, Bosserhoff A, Hellerbrand C. Characterization of glycolysis-related gene expression in malignant melanoma. Pathol Res Pract. 2019;216:152752.CrossRef
24.
Zhang Z, Li TE, Chen M, Xu D, Zhu Y, Hu BY, Lin ZF, Pan JJ, Wang X, Wu C, et al. MFN1-dependent alteration of mitochondrial dynamics drives hepatocellular carcinoma metastasis by glucose metabolic reprogramming. Br J Cancer. 2019;22(2):209–20.CrossRef
25.
Ostrom QT, Bauchet L, Davis FG, Deltour I, Fisher JL, Langer CE, Pekmezci M, Schwartzbaum JA, Turner MC, Walsh KM, et al. The epidemiology of glioma in adults: a “state of the science” review. Neuro-oncology. 2014;16(7):896–913.CrossRef
26.
Lu H, Yao B, Wen X, Jia B. FBXW7 circular RNA regulates proliferation, migration and invasion of colorectal carcinoma through NEK2, mTOR, and PTEN signaling pathways in vitro and in vivo. BMC Cancer. 2019;19(1):918.CrossRef
27.
Begum S, Yiu A, Stebbing J, Castellano L. Novel tumour suppressive protein encoded by circular RNA, circ-SHPRH, in glioblastomas. Oncogene. 2018;37(30):4055–7.CrossRef
28.
Li X, Diao H. Circular RNA circ_0001946 acts as a competing endogenous RNA to inhibit glioblastoma progression by modulating miR-671-5p and CDR1. BMC Cancer. 2019;234(8):13807–19.
29.
Lv X, Wang M, Qiang J, Guo S. Circular RNA circ-PITX1 promotes the progression of glioblastoma by acting as a competing endogenous RNA to regulate miR-379-5p/MAP3K2 axis. Eur J Pharmacol. 2019;863:172643.CrossRef
30.
Zhang Y, Li X, Zhou D, Zhi H, Wang P, Gao Y, Guo M, Yue M, Wang Y, Shen W, et al. Inferences of individual drug responses across diverse cancer types using a novel competing endogenous RNA network. Mol Oncol. 2018;12(9):1429–46.CrossRef
31.
Zhan L, Mu Z. Elevation of circ-PITX1 upregulates interleukin 17 receptor D expression via sponging miR-518a-5p and facilitates cell progression in glioma. J Cell Biochem. 2019;120(10):16495–502.CrossRef
32.
Xiao B, Tan L, He B, Liu Z, Xu R. MiRNA-329 targeting E2F1 inhibits cell proliferation in glioma cells. J Transl Med. 2013;11:172.CrossRef
33.
Kim D, Chang HR, Baek D. Rules for functional microRNA targeting. BMB Rep. 2017;50(11):554–9.CrossRef
34.
Li W, Liang J, Zhang Z, Lou H, Zhao L, Xu Y, Ou R. MicroRNA-329-3p targets MAPK1 to suppress cell proliferation, migration and invasion in cervical cancer. Oncol Rep. 2017;37(5):2743–50.CrossRef
35.
Ye Y, Zhi F, Peng Y, Yang CC. MiR-128 promotes the apoptosis of glioma cells via binding to NEK2. Eur Rev Med Pharmacol Sci. 2018;22(24):8781–8.PubMed
36.
Yao G, Yin J, Wang Q, Dong R, Lu J. Glypican-3 enhances reprogramming of glucose metabolism in liver cancer cells. Biomed Res Int. 2019;2019:2560650.PubMedPubMedCentral
Metadata
Title
Circular RNA circPITX1 knockdown inhibits glycolysis to enhance radiosensitivity of glioma cells by miR-329-3p/NEK2 axis
Authors
Yongchang Guan
Zhi Cao
Jinghua Du
Tao Liu
Tingzhong Wang
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-01169-z

Other articles of this Issue 1/2020

Cancer Cell International 1/2020 Go to the issue

Primary research

DSG2 expression is correlated with poor prognosis and promotes early-stage cervical cancer

Primary research

YY1-induced lncRNA ZFPM2-AS1 facilitates cell proliferation and invasion in small cell lung cancer via upregulating of TRAF4

Primary research

Circ_0000285 regulates proliferation, migration, invasion and apoptosis of osteosarcoma by miR-409-3p/IGFBP3 axis

Primary research

Podoplanin is indispensable for cell motility and platelet-induced epithelial-to-mesenchymal transition-related gene expression in esophagus squamous carcinoma TE11A cells

Primary research

Identification of key biomarkers associated with cell adhesion in multiple myeloma by integrated bioinformatics analysis

Primary research

RETRACTED ARTICLE: Aging-related tumor associated fibroblasts changes could worsen the prognosis of GBM patients
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits