Circ_CLIP2 promotes glioma progression through targeting the miR-195-5p/HMGB3 axis.

Cell Proliferation Glioma / genetics HMGB3 Protein Humans MicroRNAs / genetics RNA, Circular beta Catenin
Apoptosis Circ_CLIP2 Glioma HMGB3 Proliferation Wnt/β-catenin signaling pathway miR-195-5p

Journal

Journal of neuro-oncology
ISSN: 1573-7373
Titre abrégé: J Neurooncol
Pays: United States
ID NLM: 8309335

Informations de publication

Date de publication:
Sep 2021
Historique:
received: 28 05 2021
accepted: 23 07 2021
pubmed: 7 8 2021
medline: 8 2 2022
entrez: 6 8 2021
Statut: ppublish

Résumé

Circular RNA (circRNA) has been demonstrated to play key roles in regulating glioma progression. Understanding the regulatory mechanism of circRNA in glioma is vital to reveal the pathogenesis of glioma and develop novel therapeutic strategies. Therefore, our study focuses on the role and underlying mechanism of Circ_CLIP2 in glioma. The expression of Circ_CLIP2, miR-195-5p and HMGB3 in glioma cells and tissues were analyzed using qRT-PCR. Cell proliferation was determined with colony formation and MTT assays. Cell cycle and apoptosis were examined by flow cytometry. Western blot was conducted for analyzing HMGB3, PCNA, Bax, Bcl-2, cleaved-caspase 3, Wnt-1 and β-catenin. Dual-luciferase reporter assay was measured to investigate the interaction among Circ_CLIP2, miR-195-5p and HMGB3. The expression of Circ_CLIP2 and HMGB3 were increased while miR-195-5p was down-regulated in glioma cells and patients. Silencing of Circ_CLIP2 inhibited cell proliferation, enhanced cell apoptosis and inhibited the Wnt/β-catenin signaling pathway. Circ_CLIP2 suppressed miR-195-5p expression by directly sponging miR-195-5p. MiR-195-5p inhibited HMGB3 expression via directly targeting HMGB3. Knockdown of miR-195-5p facilitated cell proliferation, inhibited cell apoptosis and activated Wnt/β-catenin signaling, which were reversed by silencing of HMGB3. Knockdown of Circ_CLIP2 suppresses glioma progression by targeting miR-195-5p/HMGB3 thus inhibiting Wnt/β-catenin signaling. This study may provide potential therapeutic targets against glioma.

Sections du résumé

BACKGROUND BACKGROUND
Circular RNA (circRNA) has been demonstrated to play key roles in regulating glioma progression. Understanding the regulatory mechanism of circRNA in glioma is vital to reveal the pathogenesis of glioma and develop novel therapeutic strategies. Therefore, our study focuses on the role and underlying mechanism of Circ_CLIP2 in glioma.
METHODS METHODS
The expression of Circ_CLIP2, miR-195-5p and HMGB3 in glioma cells and tissues were analyzed using qRT-PCR. Cell proliferation was determined with colony formation and MTT assays. Cell cycle and apoptosis were examined by flow cytometry. Western blot was conducted for analyzing HMGB3, PCNA, Bax, Bcl-2, cleaved-caspase 3, Wnt-1 and β-catenin. Dual-luciferase reporter assay was measured to investigate the interaction among Circ_CLIP2, miR-195-5p and HMGB3.
RESULTS RESULTS
The expression of Circ_CLIP2 and HMGB3 were increased while miR-195-5p was down-regulated in glioma cells and patients. Silencing of Circ_CLIP2 inhibited cell proliferation, enhanced cell apoptosis and inhibited the Wnt/β-catenin signaling pathway. Circ_CLIP2 suppressed miR-195-5p expression by directly sponging miR-195-5p. MiR-195-5p inhibited HMGB3 expression via directly targeting HMGB3. Knockdown of miR-195-5p facilitated cell proliferation, inhibited cell apoptosis and activated Wnt/β-catenin signaling, which were reversed by silencing of HMGB3.
CONCLUSION CONCLUSIONS
Knockdown of Circ_CLIP2 suppresses glioma progression by targeting miR-195-5p/HMGB3 thus inhibiting Wnt/β-catenin signaling. This study may provide potential therapeutic targets against glioma.

Identifiants

DOI: 10.1007/s11060-021-03814-7 PMID: 34357490
pubmed: 34357490
doi: 10.1007/s11060-021-03814-7
pii: 10.1007/s11060-021-03814-7
doi:

Substances chimiques

HMGB3 Protein 0
MIRN195 microRNA, human 0
MicroRNAs 0
RNA, Circular 0
beta Catenin 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

131-144

Subventions

Organisme : Jiangxi provincial department of education natural science foundation youth project
ID : GJJ180153
Organisme : Science and technology plan of Jiangxi provincial health commission
ID : 20201063
Organisme : National Natural Science Foundation of China
ID : 81760445

Informations de copyright

© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Références

Reni M, Mazza E, Zanon S, Gatta G, Vecht CJ (2017) Central nervous system gliomas. Crit Rev Oncol Hematol 113:213–234. https://doi.org/10.1016/j.critrevonc.2017.03.021
doi: 10.1016/j.critrevonc.2017.03.021 pubmed: 28427510
Ostrom QT, Bauchet L, Davis FG, Deltour I, Fisher JL, Langer CE, Pekmezci M, Schwartzbaum JA, Turner MC, Walsh KM, Wrensch MR, Barnholtz-Sloan JS (2014) The epidemiology of glioma in adults: a “state of the science” review. Neuro Oncol 16:896–913. https://doi.org/10.1093/neuonc/nou087
doi: 10.1093/neuonc/nou087 pubmed: 24842956 pmcid: 4057143
Chen R, Smith-Cohn M, Cohen AL, Colman H (2017) Glioma Subclassifications and their clinical significance. Neurotherapeutics 14:284–297. https://doi.org/10.1007/s13311-017-0519-x
doi: 10.1007/s13311-017-0519-x pubmed: 28281173 pmcid: 5398991
Chowdhary MM, Ene CI, Silbergeld DL (2015) Treatment of gliomas: how did we get here? Surg Neurol Int 6:S85-88. https://doi.org/10.4103/2152-7806.151348
doi: 10.4103/2152-7806.151348 pubmed: 25722937 pmcid: 4338482
Li F, Liu Z, Sun H, Li C, Wang W, Ye L, Yan C, Tian J, Wang H (2020) PCC0208017, a novel small-molecule inhibitor of MARK3/MARK4, suppresses glioma progression in vitro and in vivo. Acta pharmaceutica Sinica B 10:289–300. https://doi.org/10.1016/j.apsb.2019.09.004
doi: 10.1016/j.apsb.2019.09.004 pubmed: 32082974
He ZQ, Duan H, Ke C, Zhang XH, Guo CC, Al-Nahari F, Zhang J, Chen ZH, Chen YS, Liu ZG, Wang J, Chen ZP, Jiang XB, Mou YG (2017) Evaluation of cumulative prognostic score based on pretreatment plasma fibrinogen and serum albumin levels in patients with newly diagnosed high-grade gliomas. Oncotarget 8:49605–49614. https://doi.org/10.18632/oncotarget.17849
doi: 10.18632/oncotarget.17849 pubmed: 28548947 pmcid: 5564791
Steinbach JP, Weller M (2004) Apoptosis in gliomas: molecular mechanisms and therapeutic implications. J Neurooncol 70:245–254. https://doi.org/10.1007/s11060-004-2753-4
doi: 10.1007/s11060-004-2753-4 pubmed: 15674481
Sun J, Li B, Shu C, Ma Q, Wang J (2020) Functions and clinical significance of circular RNAs in glioma. Mol Cancer 19:34. https://doi.org/10.1186/s12943-019-1121-0
doi: 10.1186/s12943-019-1121-0 pubmed: 32061256 pmcid: 7023692
Rynkeviciene R, Simiene J, Strainiene E, Stankevicius V, Usinskiene J, Miseikyte Kaubriene E, Meskinyte I, Cicenas J, Suziedelis K (2018) Non-Coding RNAs in Glioma. Cancers. https://doi.org/10.3390/cancers11010017
doi: 10.3390/cancers11010017 pubmed: 30583549 pmcid: 6356972
Mizoguchi M, Guan Y, Yoshimoto K, Hata N, Amano T, Nakamizo A, Sasaki T (2012) MicroRNAs in human malignant gliomas. J Oncol. https://doi.org/10.1155/2012/732874
doi: 10.1155/2012/732874 pubmed: 22848219 pmcid: 3400374
Zhang X, Yang H, Zhao L, Li G, Duan Y (2019) Circular RNA PRKCI promotes glioma cell progression by inhibiting microRNA-545. Cell Death Dis 10:616. https://doi.org/10.1038/s41419-019-1863-z
doi: 10.1038/s41419-019-1863-z pubmed: 31409777 pmcid: 6692337
Song X, Zhang N, Han P, Moon BS, Lai RK, Wang K, Lu W (2016) Circular RNA profile in gliomas revealed by identification tool UROBORUS. Nucleic Acids Res 44:e87. https://doi.org/10.1093/nar/gkw075
doi: 10.1093/nar/gkw075 pubmed: 26873924 pmcid: 4872085
Wang X, Li XD, Fu Z, Zhou Y, Huang X, Jiang X (2020) Long noncoding RNA LINC00473/miR1955p promotes glioma progression via YAP1TEAD1Hippo signaling. Int J Oncol 56:508–521. https://doi.org/10.3892/ijo.2019.4946
doi: 10.3892/ijo.2019.4946 pubmed: 31894297
Jia Y, Tian Y, An S, Yang D (2020) Effects of microRNA-195 on the prognosis of glioma patients and the proliferation and apoptosis of human glioma cells. Pathology Oncology Research: POR 26:753–763. https://doi.org/10.1007/s12253-019-00622-3
doi: 10.1007/s12253-019-00622-3 pubmed: 30806889
Wang Y, Mo Y, Gong Z, Yang X, Yang M, Zhang S, Xiong F, Xiang B, Zhou M, Liao Q, Zhang W, Li X, Li X, Li Y, Li G, Zeng Z, Xiong W (2017) Circular RNAs in human cancer. Mol Cancer 16:25. https://doi.org/10.1186/s12943-017-0598-7
doi: 10.1186/s12943-017-0598-7 pubmed: 28143578 pmcid: 5282898
Nemeth MJ, Curtis DJ, Kirby MR, Garrett-Beal LJ, Seidel NE, Cline AP, Bodine DM (2003) Hmgb3: an HMG-box family member expressed in primitive hematopoietic cells that inhibits myeloid and B-cell differentiation. Blood 102:1298–1306. https://doi.org/10.1182/blood-2002-11-3541
doi: 10.1182/blood-2002-11-3541 pubmed: 12714519
Liu J, Wang L, Li X (2018) HMGB3 promotes the proliferation and metastasis of glioblastoma and is negatively regulated by miR-200b-3p and miR-200c-3p. Cell Biochem Funct 36:357–365. https://doi.org/10.1002/cbf.3355
doi: 10.1002/cbf.3355 pubmed: 30232806
Li Y, Ma Y, Zhang T, Feng C, Liu Y (2020) High-mobility group box 3 (HMGB3) silencing inhibits non-small cell lung cancer development through regulating Wnt/beta-catenin pathway. Biol Chem. https://doi.org/10.1515/hsz-2020-0144
doi: 10.1515/hsz-2020-0144 pubmed: 33544474
Mu F, Huang J, Xing T, Jing Y, Cui T, Guo Y, Yan X, Li H, Wang N (2019) The Wnt/beta-catenin/LEF1 pathway promotes cell proliferation at least in part through direct upregulation of miR-17-92 cluster. Front Genet 10:525. https://doi.org/10.3389/fgene.2019.00525
doi: 10.3389/fgene.2019.00525 pubmed: 31191623 pmcid: 6549003
Clevers H (2006) Wnt/beta-catenin signaling in development and disease. Cell 127:469–480. https://doi.org/10.1016/j.cell.2006.10.018
doi: 10.1016/j.cell.2006.10.018 pubmed: 17081971
Panda AC (2018) Circular RNAs Act as miRNA sponges. Adv Exp Med Biol 1087:67–79. https://doi.org/10.1007/978-981-13-1426-1_6
doi: 10.1007/978-981-13-1426-1_6 pubmed: 30259358
Chen TY, Liu Y, Chen L, Luo J, Zhang C, Shen XF (2020) Identification of the potential biomarkers in patients with glioma: a weighted gene co-expression network analysis. Carcinogenesis 41:743–750. https://doi.org/10.1093/carcin/bgz194
doi: 10.1093/carcin/bgz194 pubmed: 31761927
Liu J, Zhao K, Huang N, Zhang N (2019) Circular RNAs and human glioma. Cancer Biol Med 16:11–23. https://doi.org/10.20892/j.issn.2095-3941.2018.0425
doi: 10.20892/j.issn.2095-3941.2018.0425 pubmed: 31119043 pmcid: 6528446
Wang R, Zhang S, Chen X, Li N, Li J, Jia R, Pan Y, Liang H (2018) CircNT5E Acts as a sponge of miR-422a to promote glioblastoma tumorigenesis. Cancer Res 78:4812–4825. https://doi.org/10.1158/0008-5472.CAN-18-0532
doi: 10.1158/0008-5472.CAN-18-0532 pubmed: 29967262
Li M, Li J, Liu L, Li W, Yang Y, Yuan J (2013) MicroRNA in human glioma cancers (Basel) 5:1306–1331. https://doi.org/10.3390/cancers5041306
doi: 10.3390/cancers5041306
Wang BC, Ma J (2015) Role of NicroRNAs in malignant glioma. Chin Med J (Engl) 128:1238–1244. https://doi.org/10.4103/0366-6999.156141
doi: 10.4103/0366-6999.156141
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 38:398. https://doi.org/10.1186/s13046-019-1376-8
doi: 10.1186/s13046-019-1376-8 pubmed: 31511040 pmcid: 6737709
Yilaz Susluer S, Biray Avci C, Dodurga Y, Ozlem Dogan Sigva Z, Oktar N, Gunduz C (2015) Downregulation of miR-195 via cyclosporin A in human glioblastoma cells. J BUON 20:1337–1340
pubmed: 26537083
Hui W, Yuntao L, Lun L, WenSheng L, ChaoFeng L, HaiYong H, Yueyang B (2013) MicroRNA-195 inhibits the proliferation of human glioma cells by directly targeting cyclin D1 and cyclin E1. PloS ONE 8:e54932. https://doi.org/10.1371/journal.pone.0054932
doi: 10.1371/journal.pone.0054932 pubmed: 23383003 pmcid: 3557299
Kulcheski FR, Christoff AP, Margis R (2016) Circular RNAs are miRNA sponges and can be used as a new class of biomarker. J Biotechnol 238:42–51. https://doi.org/10.1016/j.jbiotec.2016.09.011
doi: 10.1016/j.jbiotec.2016.09.011 pubmed: 27671698
Song N, Wang B, Feng G, Duan L, Yuan S, Jia W, Liu Y (2019) Knockdown of high mobility group box 3 impairs cell viability and colony formation but increases apoptosis in A549 human non-small cell lung cancer cells. Oncol Lett 17:2937–2945. https://doi.org/10.3892/ol.2019.9927
doi: 10.3892/ol.2019.9927 pubmed: 30854071 pmcid: 6365971
Gu J, Xu T, Huang QH, Zhang CM, Chen HY (2019) HMGB3 silence inhibits breast cancer cell proliferation and tumor growth by interacting with hypoxia-inducible factor 1alpha. Cancer Manag Res 11:5075–5089. https://doi.org/10.2147/CMAR.S204357
doi: 10.2147/CMAR.S204357 pubmed: 31213919 pmcid: 6549700
Kang R, Chen R, Zhang Q, Hou W, Wu S, Cao L, Huang J, Yu Y, Fan XG, Yan Z, Sun X, Wang H, Wang Q, Tsung A, Billiar TR, Zeh HJ 3rd, Lotze MT, Tang D (2014) HMGB1 in health and disease. Mol Aspects Med 40:1–116. https://doi.org/10.1016/j.mam.2014.05.001
doi: 10.1016/j.mam.2014.05.001 pubmed: 25010388
Wang P, Zhang L, Yin S, Xu Y, Tai S, Zhang LI, Liang C (2021) hsa_circ_0062019 promotes the proliferation, migration, and invasion of prostate cancer cells via the miR-195-5p/HMGA2 axis. Acta Biochim Biophys Sin 53:815–822. https://doi.org/10.1093/abbs/gmab058
doi: 10.1093/abbs/gmab058 pubmed: 33978716
Pang B, Fan H, Zhang IY, Liu B, Feng B, Meng L, Zhang R, Sadeghi S, Guo H, Pang Q (2012) HMGA1 expression in human gliomas and its correlation with tumor proliferation, invasion and angiogenesis. J Neurooncol 106:543–549. https://doi.org/10.1007/s11060-011-0710-6
doi: 10.1007/s11060-011-0710-6 pubmed: 21984063
Zeng Y, Que T, Lin J, Zhan Z, Xu A, Wu Z, Xie C, Luo J, Ding S, Long H, Zhang X, Song Y (2021) Oncogenic ZEB2/miR-637/HMGA1 signaling axis targeting vimentin promotes the malignant phenotype of glioma. Mol Ther Nucl acids 23:769–782. https://doi.org/10.1016/j.omtn.2020.12.029
doi: 10.1016/j.omtn.2020.12.029
Wang J, Xu X, Mo S, Tian Y, Wu J, Zhang J, Zhao J (2016) Involvement of microRNA-1297, a new regulator of HMGA1, in the regulation of glioma cell growth in vivo and in vitro. Am J Transl Res 8:2149–2158
pubmed: 27347322 pmcid: 4891427
Puca F, Tosti N, Federico A, Kuzay Y, Pepe A, Morlando S, Savarese T, D’Alessio F, Colamaio M, Sarnataro D, Ziberi S, De Martino M, Fusco A, Battista S (2019) HMGA1 negatively regulates NUMB expression at transcriptional and post transcriptional level in glioblastoma stem cells. Cell Cycle 18:1446–1457. https://doi.org/10.1080/15384101.2019.1618541
doi: 10.1080/15384101.2019.1618541 pubmed: 31116627 pmcid: 6592240
Bilir B, Kucuk O, Moreno CS (2013) Wnt signaling blockage inhibits cell proliferation and migration, and induces apoptosis in triple-negative breast cancer cells. J Transl Med 11:280. https://doi.org/10.1186/1479-5876-11-280
doi: 10.1186/1479-5876-11-280 pubmed: 24188694 pmcid: 4228255
Lu C, Jia S, Zhao S, Shao X (2019) MiR-342 regulates cell proliferation and apoptosis in hepatocellular carcinoma through Wnt/beta-catenin signaling pathway. Cancer Biomark 25:115–126. https://doi.org/10.3233/CBM-192399
doi: 10.3233/CBM-192399 pubmed: 31006667
Garg M, Maurya N (2019) WNT/beta-catenin signaling in urothelial carcinoma of bladder. World J Nephrol 8:83–94. https://doi.org/10.5527/wjn.v8.i5.83
doi: 10.5527/wjn.v8.i5.83 pubmed: 31624709 pmcid: 6794554

Auteurs

Bing Xiao (B)

Department of Neurosurgery, Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, Jiangxi Province, People's Republic of China.

Shi-Gang Lv (SG)

Department of Neurosurgery, Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, Jiangxi Province, People's Republic of China.

Miao-Jing Wu (MJ)

Department of Neurosurgery, Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, Jiangxi Province, People's Republic of China.

Xiao-Li Shen (XL)

Department of Neurosurgery, Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, Jiangxi Province, People's Republic of China.

Wei Tu (W)

Department of Neurosurgery, Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, Jiangxi Province, People's Republic of China.

Min-Hua Ye (MH)

Department of Neurosurgery, Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, Jiangxi Province, People's Republic of China. yywwmhe23@163.com.

Xin-Gen Zhu (XG)

Department of Neurosurgery, Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, Jiangxi Province, People's Republic of China. zzhhxxg128@163.com.
ORCID: 0000-0002-9939-7604

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › Circ_CLIP2 promotes glioma progression through...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs du tissu nerveux › Tumeurs neuroectodermiques › Tumeurs neuroépitheliales › Gliome › Circ_CLIP2 promotes glioma progression through...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Nucléoprotéines › Protéines chromosomiques nonhistones › Protéines HMG › Protéines HMGB › Protéine HMGB3 › Circ_CLIP2 promotes glioma progression through...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Circ_CLIP2 promotes glioma progression through...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN non traduit › Petit ARN non traduit › microARN › Circ_CLIP2 promotes glioma progression through...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN circulaire › Circ_CLIP2 promotes glioma progression through...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › bêta-Caténine › Circ_CLIP2 promotes glioma progression through...