MicroRNA‑432 inhibits the aggressiveness of glioblastoma multiforme by directly targeting IGF‑1R Retraction in /10.3892/ijmm.2022.5187

Chen,Xudong; Zhang,Xufei; Sun,Shunjin; Zhu,Meixiao

doi:10.3892/ijmm.2019.4429

MicroRNA‑432 inhibits the aggressiveness of glioblastoma multiforme by directly targeting IGF‑1R

Retraction in: /10.3892/ijmm.2022.5187

Authors:
- Xudong Chen
- Xufei Zhang
- Shunjin Sun
- Meixiao Zhu
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Affiliations: Department of Neurosurgery, Sixth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang 323000, P.R. China, Laboratory Animal Center, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China, Department of TCM Pharmacy, Sixth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang 323000, P.R. China
Published online on: December 16, 2019 https://doi.org/10.3892/ijmm.2019.4429
Pages: 597-606

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Abstract

MicroRNA‑432 (miR‑432) has been studied in multiple tumors, but the expression status, biological functions and the mechanism of action of miR‑432 in glioblastoma multiforme (GBM) are yet to be elucidated. In the present study, miR‑432 expression in GBM was determined and its clinical significance was evaluated among patients with GBM. The effects on the malignancy of GBM in vitro and in vivo were examined in detail and the interactions between miR‑432 and insulin‑like growth factor 1 receptor (IGF‑1R) mRNA were then explored. miR‑432 expression in GBM tissue samples and cell lines was measured by reverse transcription‑quantitative (RT‑q)PCR. GBM cell proliferation, apoptosis, migration and invasion in vitro and tumor growth in vivo were evaluated by a Cell Counting Kit‑8 assay, flow‑cytometric analysis, Transwell migration and invasion assays, and a tumor xenograft experiment, respectively. Bioinformatic analysis followed by a luciferase reporter assay, RT‑qPCR and western blotting was applied to demonstrate that IGF‑1R is a direct target gene of miR‑432 in GBM cells. It was found that miR‑432 is downregulated in GBM tumors and cell lines. miR‑432 under expression obviously correlated with the Karnofsky Performance Status score and shorter overall survival among patients with GBM. Exogenous miR‑432 expression significantly reduced proliferation and induced apoptosis of GBM cells. In addition, miR‑432 overexpression impaired the migratory and invasive abilities of GBM cells in vitro and decreased their tumor growth in vivo. Furthermore, IGF‑1R was validated as a direct target gene of miR‑432 in GBM cells. IGF‑1R knockdown imitated the tumor‑suppressive actions of miR‑432 overexpression in GBM cells. Rescue experiments proved IGF‑1R downregulation to be essential for the effects of miR‑432 on GBM cells. The results of the present study revealed a tumor‑suppressive role of the miR‑432‑IGF‑1R axis in GBM cells and this axis may have implications for GBM therapy.

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1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
2	Thorne AH, Zanca C and Furnari F: Epidermal growth factor receptor targeting and challenges in glioblastoma. Neuro Oncol. 18:914–918. 2016. View Article : Google Scholar : PubMed/NCBI
3	Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, et al: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 352:987–996. 2005. View Article : Google Scholar : PubMed/NCBI
4	Van Meir EG, Hadjipanayis CG, Norden AD, Shu HK, Wen PY and Olson JJ: Exciting new advances in neuro-oncology: The avenue to a cure for malignant glioma. CA Cancer J Clin. 60:166–193. 2010. View Article : Google Scholar : PubMed/NCBI
5	Furnari FB, Fenton T, Bachoo RM, Mukasa A, Stommel JM, Stegh A, Hahn WC, Ligon KL, Louis DN, Brennan C, et al: Malignant astrocytic glioma: Genetics, biology, and paths to treatment. Genes Dev. 21:2683–2710. 2007. View Article : Google Scholar : PubMed/NCBI
6	Zhuang W, Qin Z and Liang Z: The role of autophagy in sensitizing malignant glioma cells to radiation therapy. Acta Biochim Biophys Sin (Shanghai). 41:341–351. 2009. View Article : Google Scholar
7	Wang Y and Jiang T: Understanding high grade glioma: Molecular mechanism, therapy and comprehensive management. Cancer Lett. 331:139–146. 2013. View Article : Google Scholar : PubMed/NCBI
8	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
9	Esquela-Kerscher A and Slack FJ: Oncomirs-microRNAs with a role in cancer. Nat Rev Cancer. 6:259–269. 2006. View Article : Google Scholar : PubMed/NCBI
10	Shi L, Yuan Y and Li HY: MicroRNA-139-3p suppresses growth and metastasis of glioblastoma via inhibition of NIN1/RPNI2 binding protein 1 homolog. Eur Rev Med Pharmacol Sci. 23:4264–4274. 2019.PubMed/NCBI
11	Zuo J, Yu H, Xie P, Liu W, Wang K and Ni H: miR-454-3p exerts tumor-suppressive functions by down-regulation of NFATc2 in glioblastoma. Gene. 710:233–239. 2019. View Article : Google Scholar : PubMed/NCBI
12	Yang F, Zhang C, Xu C, Fu F, Han D and Li H: MicroRNA-559 plays an inhibitory role in the malignant progression of glio-blastoma cells by directly targeting metadherin. Onco Targets Ther. 12:4415–4426. 2019. View Article : Google Scholar :
13	Zhou X, Wu W, Zeng A, Nie E, Jin X, Yu T, Zhi T, Jiang K, Wang Y, Zhang J and You Y: MicroRNA-141-3p promotes glioma cell growth and temozolomide resistance by directly targeting p53. Oncotarget. 8:71080–71094. 2017.PubMed/NCBI
14	Liu Z, Su D, Qi X and Ma J: MiR-500a-5p promotes glioblastoma cell proliferation, migration and invasion by targeting chromodomain helicase DNA binding protein 5. Mol Med Rep. 18:2689–2696. 2018.PubMed/NCBI
15	Cui T, Bell EH, McElroy J, Becker AP, Gulati PM, Geurts M, Mladkova N, Gray A, Liu K, Yang L, et al: miR-4516 predicts poor prognosis and functions as a novel oncogene via targeting PTPN14 in human glioblastoma. Oncogene. 38:2923–2936. 2019. View Article : Google Scholar :
16	Huang SW, Ali ND, Zhong L and Shi J: MicroRNAs as biomarkers for human glioblastoma: Progress and potential. Acta Pharmacol Sin. 39:1405–1413. 2018. View Article : Google Scholar : PubMed/NCBI
17	Banelli B, Forlani A, Allemanni G, Morabito A, Pistillo MP and Romani M: MicroRNA in glioblastoma: An overview. Int J Genomics. 2017:76390842017. View Article : Google Scholar : PubMed/NCBI
18	Ahir BK, Ozer H, Engelhard HH and Lakka SS: MicroRNAs in glioblastoma pathogenesis and therapy: A comprehensive review. Crit Rev Oncol Hematol. 120:22–33. 2017. View Article : Google Scholar : PubMed/NCBI
19	Chen L, Kong G, Zhang C, Dong H, Yang C, Song G, Guo C, Wang L and Yu H: MicroRNA-432 functions as a tumor suppressor gene through targeting E2F3 and AXL in lung adenocarcinoma. Oncotarget. 7:20041–20053. 2016.PubMed/NCBI
20	Lv D, Zhen Z and Huang D: MicroRNA-432 is downregulated in osteosarcoma and inhibits cell proliferation and invasion by directly targeting metastasis-associated in colon cancer-1. Exp Ther Med. 17:919–926. 2019.PubMed/NCBI
21	Jiang N, Chen WJ, Zhang JW, Xu C, Zeng XC, Zhang T, Li Y and Wang GY: Downregulation of miR-432 activates Wnt/β-catenin signaling and promotes human hepatocellular carcinoma proliferation. Oncotarget. 6:7866–7879. 2015.PubMed/NCBI
22	Das E and Bhattacharyya NP: MicroRNA-432 contributes to dopamine cocktail and retinoic acid induced differentiation of human neuroblastoma cells by targeting NESTIN and RCOR1 genes. FEBS Lett. 588:1706–1714. 2014. View Article : Google Scholar : PubMed/NCBI
23	Li JB, Liu F, Zhang BP, Bai WK, Cheng W, Zhang YH and Yu LJ: LncRNA625 modulates prostate cancer cells proliferation and apoptosis through regulating the Wnt/β-catenin pathway by targeting miR-432. Eur Rev Med Pharmacol Sci. 21:2586–2595. 2017.PubMed/NCBI
24	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar
25	Baradaran Rahimi V, Askari VR, Tajani AS, Hosseini A and Rakhshandeh H: Evaluation of the sleep-prolonging effect of lagenaria vulgaris and cucurbita pepo extracts on pentobar-bital-induced sleep and possible mechanisms of action. Medicina (Kaunas). 54:pii: E55. 2018.
26	Maris C, D'Haene N, Trépant AL, Le Mercier M, Sauvage S, Allard J, Rorive S, Demetter P, Decaestecker C and Salmon I: IGF-IR: A new prognostic biomarker for human glioblastoma. Br J Cancer. 113:729–737. 2015. View Article : Google Scholar : PubMed/NCBI
27	Shi ZM, Wang XF, Qian X, Tao T, Wang L, Chen QD, Wang XR, Cao L, Wang YY, Zhang JX, et al: MiRNA-181b suppresses IGF-1R and functions as a tumor suppressor gene in gliomas. RNA. 19:552–560. 2013. View Article : Google Scholar : PubMed/NCBI
28	Zhang Y, Chen X, Lian H, Liu J, Zhou B, Han S, Peng B, Yin J, Liu W and He X: MicroRNA-503 acts as a tumor suppressor in glioblastoma for multiple antitumor effects by targeting IGF-1R. Oncology reports. 31:1445–1452. 2014. View Article : Google Scholar : PubMed/NCBI
29	Guo T, Feng Y, Liu Q, Yang X, Jiang T, Chen Y and Zhang Q: MicroRNA-320a suppresses in GBM patients and modulates glioma cell functions by targeting IGF-1R. Tumour Biol. 35:11269–11275. 2014. View Article : Google Scholar : PubMed/NCBI
30	Wang B, Sun F, Dong N, Sun Z, Diao Y, Zheng C, Sun J, Yang Y and Jiang D: MicroRNA-7 directly targets insulin-like growth factor 1 receptor to inhibit cellular growth and glucose metabolism in gliomas. Diagn Pathol. 9:2112014. View Article : Google Scholar : PubMed/NCBI
31	Lian HW, Zhou Y, Jian ZH and Liu RZ: MiR-323-5p acts as a tumor suppressor by targeting the insulin-like growth factor 1 receptor in human glioma cells. Asian Pac J Cancer Prev. 15:10181–10185. 2014. View Article : Google Scholar
32	Lin YC, Hou SC, Hung CM, Lin JN, Chen WC, Ho CT, Kuo SC and Way TD: Inhibition of the insulin-like growth factor 1 receptor by CHM-1 blocks proliferation of glioblastoma multiforme cells. Chem Biol Interact. 231:119–126. 2015. View Article : Google Scholar : PubMed/NCBI
33	Ma Y, Tang N, Thompson RC, Mobley BC, Clark SW, Sarkaria JN and Wang J: InsR/IGF1R pathway mediates resistance to EGFR inhibitors in glioblastoma. Clin Cancer Res. 22:1767–1776. 2016. View Article : Google Scholar :
34	Yu J, Wu SW and Wu WP: A tumor-suppressive microRNA, miRNA-485-5p, inhibits glioma cell proliferation and invasion by down-regulating TPD52L2. Am J Transl Res. 9:3336–3344. 2017.PubMed/NCBI
35	Xu X, Cai N, Zhi T, Bao Z, Wang D, Liu Y, Jiang K, Fan L, Ji J and Liu N: MicroRNA-1179 inhibits glioblastoma cell proliferation and cell cycle progression via directly targeting E2F transcription factor 5. Am J Cancer Res. 7:1680–1692. 2017.PubMed/NCBI
36	Cheng ZX, Yin WB and Wang ZY: MicroRNA-132 induces temozolomide resistance and promotes the formation of cancer stem cell phenotypes by targeting tumor suppressor candidate 3 in glioblastoma. Int J Mol Med. 40:1307–1314. 2017. View Article : Google Scholar : PubMed/NCBI
37	Zhang Y, Cruickshanks N, Pahuski M, Yuan F, Dutta A, Schiff D, Purow B and Abounader R: Noncoding RNAs in glioblastoma. Glioblastoma. De Vleeschouwer S: Codon Publications; Brisbane, AU: 2017, View Article : Google Scholar