MicroRNA‑186 targets IGF‑1R and exerts tumor‑suppressing functions in glioma Retraction in /10.3892/mmr.2022.12778

Jiang,Jian; Wang,Weijie; Fang,Dazhao; Jin,Xiaodong; Ding,Lianshu; Sun,Xiaoyang

doi:10.3892/mmr.2017.7586

November-2017 Volume 16 Issue 5

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

November-2017 Volume 16 Issue 5

Full Size Image

Article

MicroRNA‑186 targets IGF‑1R and exerts tumor‑suppressing functions in glioma

Retraction in: /10.3892/mmr.2022.12778

Authors:
- Jian Jiang
- Weijie Wang
- Dazhao Fang
- Xiaodong Jin
- Lianshu Ding
- Xiaoyang Sun
View Affiliations / Copyright

Affiliations: Department of Neurosurgery, The Affiliated Huai'an First Hospital of Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China
Pages: 7821-7828
|
Published online on: September 21, 2017

https://doi.org/10.3892/mmr.2017.7586
Expand metrics +

Abstract

Glioma is the most common malignant brain tumor in adults and represents one of the most aggressive and life‑threatening types of cancer in humans. Increasing studies have revealed that microRNAs are abnormally expressed in various types of human cancer, and have oncogenic or tumor suppressive roles, which depend primarily on the type of cancer. The present study aimed to investigate the expression level and effects of microRNA‑186 (miR‑186) on glioma, and its underlying molecular mechanism. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis was performed to detect the expression of miR‑186 in glioma tissues and cell lines. Cell proliferation and invasion were assessed using MTT and cell invasion assays, respectively. Bioinformatics analysis and a luciferase reporter assay were performed to identify insulin‑like growth factor 1 receptor (IGF‑1R) as a novel target gene of miR‑186. The mRNA expression level of IGF‑1R was also measured using RT‑qPCR analysis. The association between miR‑186 and the expression of IGF‑1R was evaluated using Spearman's correlation analysis. Furthermore, the regulatory effects of miR‑186 on the mRNA and protein expression of IGF‑1R were determined using RT‑qPCR and western blot analyses. Finally, the biological effects of the underexpression IGF‑1R on glioma cells were investigated. The results showed that miR‑186 was significantly downregulated in glioma tissues and cell lines. Inducing the expression of miR‑186 suppressed glioma cell proliferation and invasion. IGF‑1R was confirmed as a direct target gene of miR‑186. In addition, the mRNA expression of IGF‑1R was upregulated and inversely correlated with that of miR‑186 in glioma tissues. The effects of IGF‑1R‑knockdown on glioma cell proliferation and invasion were similar to the effects induced by the overexpression of miR‑186. These findings demonstrated that miR‑186 acted as a tumor suppressor by targeting IGF‑1R in glioma, suggesting miR‑186 may be a potential therapeutic target for the treatment of this disease.

View Figures

View References

1	Taylor LP: Diagnosis, treatment and prognosis of glioma: Five new things. Neurology. 75 18 Suppl 1:S28–S32. 2010. View Article : Google Scholar : PubMed/NCBI
2	Karsy M, Albert L, Tobias ME, Murali R and Jhanwar-Uniyal M: All-trans retinoic acid modulates cancer stem cells of glioblastoma multiforme in an MAPK-dependent manner. Anticancer Res. 30:4915–4920. 2010.PubMed/NCBI
3	Zhu GY, Shi BZ and Li Y: FoxM1 regulates Sirt1 expression in glioma cells. Eur Rev Med Pharmacol Sci. 18:205–211. 2014.PubMed/NCBI
4	Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW and Kleihues P: The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 114:97–109. 2007. View Article : Google Scholar : PubMed/NCBI
5	Xu Z, Zeng X, Tian D, Xu H, Cai Q, Wang J and Chen Q: MicroRNA-383 inhibits anchorage-independent growth and induces cell cycle arrest of glioma cells by targeting CCND1. Biochem Biophys Res Commun. 453:833–838. 2014. View Article : Google Scholar : PubMed/NCBI
6	Omuro A and DeAngelis LM: Glioblastoma and other malignant gliomas: A clinical review. JAMA. 310:1842–1850. 2013. View Article : Google Scholar : PubMed/NCBI
7	Bartel DP: MicroRNAs: Target recognition and regulatory functions. Cell. 136:215–233. 2009. View Article : Google Scholar : PubMed/NCBI
8	Shukla GC, Singh J and Barik S: MicroRNAs: Processing, maturation, target recognition and regulatory functions. Mol Cell Pharmacol. 3:83–92. 2011.PubMed/NCBI
9	Hwang HW and Mendell JT: MicroRNAs in cell proliferation, cell death, and tumorigenesis. Br J Cancer. 96 Suppl:R40–R44. 2007.PubMed/NCBI
10	Bueno MJ and Malumbres M: MicroRNAs and the cell cycle. Biochim Biophys Acta. 1812:592–601. 2011. View Article : Google Scholar : PubMed/NCBI
11	Zhang J, Gong X, Tian K, Chen D, Sun J, Wang G and Guo M: miR-25 promotes glioma cell proliferation by targeting CDKN1C. Biomed Pharmacother. 71:7–14. 2015. View Article : Google Scholar : PubMed/NCBI
12	Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, et al: MicroRNA expression profiles classify human cancers. Nature. 435:834–838. 2005. View Article : Google Scholar : PubMed/NCBI
13	Li T, Pan H and Li R: The dual regulatory role of miR-204 in cancer. Tumour Biol. 37:11667–11677. 2016. View Article : Google Scholar : PubMed/NCBI
14	Bertoli G, Cava C and Castiglioni I: The potential of miRNAs for diagnosis, treatment and monitoring of breast cancer. Scand J Clin Lab Invest Suppl. 245:34–39. 2016. View Article : Google Scholar
15	Ye L, Wang H and Liu B: miR-211 promotes non-small cell lung cancer proliferation by targeting SRCIN1. Tumour Biol. 37:1151–1157. 2016. View Article : Google Scholar : PubMed/NCBI
16	Wang CY, Hua L, Sun J, Yao KH, Chen JT, Zhang JJ and Hu JH: MiR-211 inhibits cell proliferation and invasion of gastric cancer by down-regulating SOX4. Int J Clin Exp Pathol. 8:14013–14020. 2015.PubMed/NCBI
17	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
18	Cai J, Wu J, Zhang H, Fang L, Huang Y, Yang Y, Zhu X, Li R and Li M: miR-186 downregulation correlates with poor survival in lung adenocarcinoma, where it interferes with cell-cycle regulation. Cancer Res. 73:756–766. 2013. View Article : Google Scholar : PubMed/NCBI
19	Chen F, Zhou C, Lu Y, Yuan L, Peng F, Zheng L and Li X: Expression of hsa-miR-186 and its role in human colon carcinoma cells. Nan Fang Yi Ke Da Xue Xue Bao. 33:654–660. 2013.(In Chinese). PubMed/NCBI
20	Zhang TJ, Wang YX, Yang DQ, Yao DM, Yang L, Zhou JD, Deng ZQ, Wen XM, Guo H, Ma JC, et al: Down-regulation of miR-186 correlates with poor survival in de novo acute myeloid leukemia. Clin Lab. 62:113–120. 2016. View Article : Google Scholar : PubMed/NCBI
21	He W, Feng J, Zhang Y, Wang Y, Zang W and Zhao G: microRNA-186 inhibits cell proliferation and induces apoptosis in human esophageal squamous cell carcinoma by targeting SKP2. Lab Invest. 96:317–324. 2016. View Article : Google Scholar : PubMed/NCBI
22	Liu Z, Zhang G, Yu W, Gao N and Peng J: miR-186 inhibits cell proliferation in multiple myeloma by repressing Jagged1. Biochem Biophys Res Commun. 469:692–697. 2016. View Article : Google Scholar : PubMed/NCBI
23	Ries J, Vairaktaris E, Agaimy A, Kintopp R, Baran C, Neukam FW and Nkenke E: miR-186, miR-3651 and miR-494: Potential biomarkers for oral squamous cell carcinoma extracted from whole blood. Oncol Rep. 31:1429–1436. 2014. View Article : Google Scholar : PubMed/NCBI
24	Yao K, He L, Gan Y, Zeng Q, Dai Y and Tan J: MiR-186 suppresses the growth and metastasis of bladder cancer by targeting NSBP1. Diagn Pathol. 10:1462015. View Article : Google Scholar : PubMed/NCBI
25	Wang M, Xia X, Chu W, Xia L, Meng T, Liu L and Liu Y: Roles of miR-186 and PTTG1 in colorectal neuroendocrine tumors. Int J Clin Exp Med. 8:22149–22157. 2015.PubMed/NCBI
26	Liu L, Wang Y, Bai R, Yang K and Tian Z: MiR-186 inhibited aerobic glycolysis in gastric cancer via HIF-1α regulation. Oncogenesis. 5:e2242016. View Article : Google Scholar : PubMed/NCBI
27	Ruan T, He X, Yu J and Hang Z: MicroRNA-186 targets Yes-associated protein 1 to inhibit Hippo signaling and tumorigenesis in hepatocellular carcinoma. Oncol Lett. 11:2941–2945. 2016.PubMed/NCBI
28	Cui G, Cui M, Li Y, Liang Y, Li W, Guo H and Zhao S: MiR-186 targets ROCK1 to suppress the growth and metastasis of NSCLC cells. Tumour Biol. 35:8933–8937. 2014. View Article : Google Scholar : PubMed/NCBI
29	Liu Q, Wang H, Singh A and Shou F: Expression and function of microRNA-497 in human osteosarcoma. Mol Med Rep. 14:439–445. 2016. View Article : Google Scholar : PubMed/NCBI
30	Singh RK, Gaikwad SM, Jinager A, Chaudhury S, Maheshwari A and Ray P: IGF-1R inhibition potentiates cytotoxic effects of chemotherapeutic agents in early stages of chemoresistant ovarian cancer cells. Cancer Lett. 354:254–262. 2014. View Article : Google Scholar : PubMed/NCBI
31	Chen HX and Sharon E: IGF-1R as an anti-cancer target-trials and tribulations. Chin J Cancer. 32:242–252. 2013. View Article : Google Scholar : PubMed/NCBI
32	Singh I, Amin H, Rah B and Goswami A: Targeting EGFR and IGF 1R: A promising combination therapy for metastatic cancer. Front Biosci (Schol Ed). 5:231–246. 2013. View Article : Google Scholar : PubMed/NCBI
33	Ma Y, Cheng Q, Ren Z, Xu L, Zhao Y, Sun J, Hu S and Xiao W: Induction of IGF-1R expression by EGR-1 facilitates the growth of prostate cancer cells. Cancer Lett. 317:150–156. 2012. View Article : Google Scholar : PubMed/NCBI
34	Harrington EA, Bennett MR, Fanidi A and Evan GI: c-Myc-induced apoptosis in fibroblasts is inhibited by specific cytokines. EMBO J. 13:3286–3295. 1994.PubMed/NCBI
35	Resnicoff M, Abraham D, Yutanawiboonchai W, Rotman HL, Kajstura J, Rubin R, Zoltick P and Baserga R: The insulin-like growth factor I receptor protects tumor cells from apoptosis in vivo. Cancer Res. 55:2463–2469. 1995.PubMed/NCBI
36	Ambrose D, Resnicoff M, Coppola D, Sell C, Miura M, Jameson S, Baserga R and Rubin R: Growth regulation of human glioblastoma T98G cells by insulin-like growth factor-1 and its receptor. J Cell Physiol. 159:92–100. 1994. View Article : Google Scholar : PubMed/NCBI
37	Naidu KA, Tang JL, Naidu KA, Prockop LD, Nicosia SV and Coppola D: Antiproliferative and apoptotic effect of ascorbyl stearate in human glioblastoma multiforme cells: Modulation of insulin-like growth factor-I receptor (IGF-IR) expression. J Neurooncol. 54:15–22. 2001. View Article : Google Scholar : PubMed/NCBI
38	He Z, Cen D, Luo X, Li D, Li P, Liang L and Meng Z: Downregulation of miR-383 promotes glioma cell invasion by targeting insulin-like growth factor 1 receptor. Med Oncol. 30:5572013. View Article : Google Scholar : PubMed/NCBI
39	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 : PubMed/NCBI
40	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