Suppression of miR‑106a‑5p expression inhibits tumorigenesis via increasing CELF‑2 expression in spinal cord glioma

Xu,Hao; Wang,Fei; Wang,Lin

doi:10.3892/ol.2021.12888

Suppression of miR‑106a‑5p expression inhibits tumorigenesis via increasing CELF‑2 expression in spinal cord glioma

Authors:
- Hao Xu
- Fei Wang
- Lin Wang
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Affiliations: Department of Neurosurgery, The First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui 230000, P.R. China
Published online on: June 30, 2021 https://doi.org/10.3892/ol.2021.12888
Article Number: 627
Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Spinal cord glioma is a tumor characterized by high recurrence and mortality rates, and its treatment remains a major challenge. It has been reported that abnormal expression of microRNAs (miRNAs/miRs) is associated with tumor progression. Therefore, the current study aimed to identify novel miRNAs associated with spinal cord glioma. Herein, the expression levels of several miRNAs were determined in human spinal cord glioma and adjacent non‑cancerous tissues by reverse transcription‑quantitative (RT‑qPCR). The results revealed that miR‑106a‑5p expression was markedly upregulated in spinal cord glioma tissues compared with in non‑cancerous tissues. Furthermore, the biological effects of miR‑106a‑5p on spinal cord glioma cells were evaluated by MTT, Transwell and flow cytometric assays. In 0231SCG cells transfected with miR‑106a‑5p inhibitor, cell proliferation, migration and invasion were attenuated, whereas apoptosis was enhanced. A search of the TargetScan database revealed that miR‑106a‑5p directly targeted CUGBP Elav‑like family member 2 (CELF‑2). Western blot and RT‑qPCR experiments further confirmed the association between miR‑106a‑5p and CELF‑2 expression in spinal cord glioma tissues. The current results demonstrated that CELF‑2 was a direct target of miR‑106a‑5p, and that the expression levels of CELF‑2 were negatively associated with those of miR‑106a‑5p. In addition, overexpression of CELF‑2 in spinal cord glioma cells reversed the tumor‑promoting effects of miR‑106a‑5p both in vitro and in vivo. Overall, the aforementioned findings indicated that miR‑106a‑5p, which was highly expressed in spinal cord glioma tissues, may affect the proliferation, migration, invasion and apoptosis of spinal cord glioma cells via targeting CELF‑2, thus indicating a potential approach to the future clinical management of spinal cord glioma.

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1	Ma CC, Xiong Z, Zhu GN, Wang C, Zong G, Wang HL, Bian EB and Zhao B: Long non-coding RNA ATB promotes glioma malignancy by negatively regulating miR-200a. J Exp Clin Cancer Res. 35:902016. View Article : Google Scholar : PubMed/NCBI
2	Ramaswamy V and Taylor MD: CAR T cells for childhood diffuse midline gliomas. Nat Med. 24:534–535. 2018. View Article : Google Scholar : PubMed/NCBI
3	Tobias A, Ahmed A, Moon KS and Lesniak MS: The art of gene therapy for glioma: A review of the challenging road to the bedside. J Neurol Neurosurg Psychiatry. 84:213–222. 2013. View Article : Google Scholar : PubMed/NCBI
4	Zheng YJ, Liang TS, Wang J, Zhao JY, Yang DK and Liu ZS: Silencing lncRNA LOC101928963 inhibits proliferation and promotes apoptosis in spinal cord glioma cells by binding to PMAIP1. Mol Ther Nucleic Acids. 18:485–495. 2019. View Article : Google Scholar : PubMed/NCBI
5	Alvi MA, Ida CM, Paolini MA, Kerezoudis P, Meyer J, Barr Fritcher EG, Goncalves S, Meyer FB, Bydon M and Raghunathan A: Spinal cord high-grade infiltrating gliomas in adults: Clinico-pathological and molecular evaluation. Mod Pathol. 32:1236–1243. 2019. View Article : Google Scholar : PubMed/NCBI
6	Ropper AE, Zeng X, Haragopal H, Anderson JE, Aljuboori Z, Han I, Abd-El-Barr M, Lee HJ, Sidman RL, Snyder EY, et al: Targeted treatment of experimental spinal cord glioma with dual gene-engineered human neural stem cells. Neurosurgery. 79:481–491. 2016. View Article : Google Scholar : PubMed/NCBI
7	An T, Fan T, Zhang XQ, Liu YF, Huang J, Liang C, Lv BH, Wang YQ, Zhao XG, Liu JX, et al: Comparison of alterations in miRNA expression in matched tissue and blood samples during spinal cord glioma progression. Sci Rep. 9:91692019. View Article : Google Scholar : PubMed/NCBI
8	Gebert LF and MacRae IJ: Regulation of microRNA function in animals. Nat Rev Mol Cell Biol. 20:21–37. 2019. View Article : Google Scholar : PubMed/NCBI
9	Wessels HH, Lebedeva S, Hirsekorn A, Wurmus R, Akalin A, Mukherjee N and Ohler U: Global identification of functional microRNA-mRNA interactions in Drosophila. Nat Commun. 10:16262019. View Article : Google Scholar : PubMed/NCBI
10	Moradimotlagh A, Arefian E, Valojerdi RR, Ghaemi S, Adegani FJ and Soleimani M: MicroRNA-129 inhibits glioma cell growth by targeting CDK4, CDK6, and MDM2. Mol Ther Nucleic Acids. 19:759–764. 2020. View Article : Google Scholar : PubMed/NCBI
11	Xu SJ, Hu HT, Li HL and Chang S: The role of miRNAs in immune cell development, immune cell activation, and tumor immunity: With a focus on macrophages and natural Killer cells. Cells. 8:11402019. View Article : Google Scholar : PubMed/NCBI
12	Tang L, Chen HY, Hao NB, Tang B, Guo H, Yong X, Dong H and Yang SM: microRNA inhibitors: Natural and artificial sequestration of microRNA. Cancer Lett. 407:139–147. 2017. View Article : Google Scholar : PubMed/NCBI
13	Abels ER, Maas SL, Nieland L, Wei Z, Cheah PS, Tai E, Kolsteeg CJ, Dusoswa SA, Ting DT, Hickman S, et al: Glioblastoma-associated microglia reprogramming is mediated by functional transfer of extracellular miR-21. Cell Rep. 28:3105–3119.e7. 2019. View Article : Google Scholar : PubMed/NCBI
14	Ouyang H, Gore J, Deitz S and Korc M: Erratum: microRNA-10b enhances pancreatic cancer cell invasion by suppressing TIP30 expression and promoting EGF and TGF-β actions. Oncogene. 36:4952. 2017. View Article : Google Scholar : PubMed/NCBI
15	Ye J, Yao Y, Song Q, Li S, Hu Z, Yu Y, Hu C, Da X, Li H, Chen Q and Wang QK: Up-regulation of miR-95-3p in hepatocellular carcinoma promotes tumorigenesis by targeting p21 expression. Sci Rep. 6:340342016. View Article : Google Scholar : PubMed/NCBI
16	Wang Z, Wang B, Shi Y, Xu C, Xiao HL, Ma LN, Xu SL, Yang L, Wang QL, Dang WQ, et al: Oncogenic miR-20a and miR-106a enhance the invasiveness of human glioma stem cells by directly targeting TIMP-2. Oncogene. 34:1407–1419. 2015. View Article : Google Scholar : PubMed/NCBI
17	Yan T, Ooi WF, Qamra A, Cheung A, Ma D, Sundaram GM, Xu C, Xing M, Poon L, Wang J, et al: HoxC5 and miR-615-3p target newly evolved genomic regions to repress hTERT and inhibit tumorigenesis. Nat Commun. 9:1002018. View Article : Google Scholar : PubMed/NCBI
18	Bayraktar R and Van Roosbroeck K: miR-155 in cancer drug resistance and as target for miRNA-based therapeutics. Cancer Metastasis Rev. 37:33–44. 2018. View Article : Google Scholar : PubMed/NCBI
19	Miyoshi H, Blömer U, Takahashi M, Gage FH and Verma IM: Development of a self-inactivating lentivirus vector. J Virol. 72:8150–8157. 1998. View Article : Google Scholar : PubMed/NCBI
20	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 : PubMed/NCBI
21	Luan W, Zhou Z, Ni X, Xia Y, Wang J, Yan Y and Xu B: Long non-coding RNA H19 promotes glucose metabolism and cell growth in malignant melanoma via miR-106a-5p/E2F3 axis. J Cancer Res Clin Oncol. 144:531–542. 2018. View Article : Google Scholar : PubMed/NCBI
22	He QY, Wang GC, Zhang H, Tong DK, Ding C, Liu K, Ji F, Zhu X and Yang S: miR-106a-5p suppresses the proliferation, migration, and invasion of osteosarcoma cells by targeting HMGA2. DNA Cell Biol. 35:506–520. 2016. View Article : Google Scholar : PubMed/NCBI
23	Pan YJ, Wei LL, Wu XJ, Huo FC, Mou J and Pei DS: miR-106a-5p inhibits the cell migration and invasion of renal cell carcinoma through targeting PAK5. Cell Death Dis. 8:e3155. 2017. View Article : Google Scholar : PubMed/NCBI
24	Li D, Wang Z, Chen Z, Lin L, Wang Y, Sailike D, Luo K, Du G, Xiang X and Jiafu GD: MicroRNA-106a-5p facilitates human glioblastoma cell proliferation and invasion by targeting adenomatosis polyposis coli protein. Biochem Biophys Res Commun. 481:245–250. 2016. View Article : Google Scholar : PubMed/NCBI
25	Hoey C, Ray J, Jeon J, Huang X, Taeb S, Ylanko J, Andrews DW, Boutros PC and Liu SK: miRNA-106a is a novel regulator of radiation resistance through targeting LITAF and ATM in prostate cancer. Mol Oncol. 12:1324–1341. 2018. View Article : Google Scholar : PubMed/NCBI
26	Pencheva N and Tavazoie SF: Control of metastatic progression by microRNA regulatory networks. Nat Cell Biol. 15:546–554. 2013. View Article : Google Scholar : PubMed/NCBI
27	Wang J, Liu L, Sun Y, Xue Y, Qu J, Pan S, Li H, Qu H, Wang J and Zhang J: miR-615-3p promotes proliferation and migration and inhibits apoptosis through its potential target CELF2 in gastric cancer. Biomed Pharmacother. 101:406–413. 2018. View Article : Google Scholar : PubMed/NCBI
28	Yeung YT, Fan S, Lu B, Yin S, Yang S, Nie W, Wang M, Zhou L, Li T, Li X, et al: CELF2 suppresses non-small cell lung carcinoma growth by inhibiting the PREX2-PTEN interaction. Carcinogenesis. 41:377–389. 2020. View Article : Google Scholar : PubMed/NCBI
29	Lin S and Gregory RI: MicroRNA biogenesis pathways in cancer. Nat Rev Cancer. 15:321–333. 2015. View Article : Google Scholar : PubMed/NCBI
30	Madsen CD, Hooper S, Tozluoglu M, Bruckbauer A, Fletcher G, Erler JT, Bates PA, Thompson B and Sahai E: STRIPAK components determine mode of cancer cell migration and metastasis. Nat Cell Biol. 17:68–80. 2015. View Article : Google Scholar : PubMed/NCBI
31	Fan B, Jiao BH, Fan FS, Lu SK, Song J, Guo CY, Yang JK and Yang L: Downregulation of miR-95-3p inhibits proliferation, and invasion promoting apoptosis of glioma cells by targeting CELF2. Int J Oncol. 47:1025–1033. 2015. View Article : Google Scholar : PubMed/NCBI
32	Piqué L, Martinez de Paz A, Piñeyro D, Martínez-Cardús A, Castro de Moura M, Llinàs-Arias P, Setien F, Gomez-Miragaya J, Gonzalez-Suarez E, Sigurdsson S, et al: Epigenetic inactivation of the splicing RNA-binding protein CELF2 in human breast cancer. Oncogene. 38:7106–7112. 2019. View Article : Google Scholar