[MicroRNA-218 Promotes Osteosarcoma Cell Apoptosis by Down-regulating Oncogene B Lymphoma Mouse Moloney Leukemia Virus Insertion Region 1]

Overview

Journal Nan Fang Yi Ke Da Xue Xue Bao

Specialty General Medicine

Date 2018 Jun 13

PMID 29891444

Citations 2

Authors

Gui-Hua Lai

Ai-Lan Huang

Zhi Zhao

Xing-Hao Lu

Wen-Xuan Zu

Affiliations

Soon will be listed here.

Abstract

Objective: To investigate the tumor-suppressing effect of microRNA-218 (miR-218) in osteosarcoma (OS) and explore its molecular mechanism.

Methods: We examined the expression levels of miR-218 in 68 pairs of OS and adjacent tissue samples using qRT-PCR. Cultured human OS cell line Saos-2 was transfected with miR-218 mimics or anti-miR-218 mimics, and the cell apoptosis was assessed using CCK-8 assay, annexin V-FITC staining and Western blotting. We also analyzed the potential functional targets of miR-218 in Saos-2 cells using luciferase assay, qRT-PCR and Western blotting.

Results: The expression level of miR-218 was lowered by at least 8 folds in OS tissues as compared with the adjacent tissues. In cultured Saos-2 cells, transfection with miR-218 mimics for 24, 36, and 48 h resulted in a significant reduction in the cell viability, while transfection with anti-miR-218 mimics significantly increased the cell viability. The cells transfected with miR-218 mimics showed an obviously enhanced expression of cleaved poly(ADP-ribose) polymerase (C-PARP) as compared with the cells transfected with anti-miR-218 mimics and the control cells. Flow cytometry demonstrated obviously increased apoptosis of the cells following miR-218 mimics transfection. We identified the oncogene B lymphoma mouse Moloney leukemia virus insertion region 1 (BMI-1) as a specific target of miR-218 in Saos-2 cells. BMI-1 expressions at both the mRNA and protein levels were significantly reduced in Saos-2 cells overexpressing miR-218 but increased in the cells with miR-218 knockdown as compared to the control cells. Luciferase reporter assay indicated that miR-218 directly inhibited the expression of BMI-1 via binding to its 3'-UTR in OS cells.

Conclusion: miR-218 can promote OS cell apoptosis and plays the role as a tumor suppressor by down-regulating BMI-1.

Citing Articles

The Crucial Roles of Bmi-1 in Cancer: Implications in Pathogenesis, Metastasis, Drug Resistance, and Targeted Therapies.

Xu J, Li L, Shi P, Cui H, Yang L Int J Mol Sci. 2022; 23(15).

PMID: 35897796 PMC: 9367737. DOI: 10.3390/ijms23158231.

Molecular Biology of Osteosarcoma.

Czarnecka A, Synoradzki K, Firlej W, Bartnik E, Sobczuk P, Fiedorowicz M Cancers (Basel). 2020; 12(8).

PMID: 32751922 PMC: 7463657. DOI: 10.3390/cancers12082130.

References

Isakoff M, Bielack S, Meltzer P, Gorlick R . Osteosarcoma: Current Treatment and a Collaborative Pathway to Success. J Clin Oncol. 2015; 33(27):3029-35. PMC: 4979196. DOI: 10.1200/JCO.2014.59.4895. View

Lu Y, Zhang L, Waye M, Fu W, Zhang J . MiR-218 mediates tumorigenesis and metastasis: Perspectives and implications. Exp Cell Res. 2015; 334(1):173-82. DOI: 10.1016/j.yexcr.2015.03.027. View

Zhu L, Yang S, He S, Qiang F, Cai J, Liu R . Downregulation of ubiquitin-specific protease 14 (USP14) inhibits breast cancer cell proliferation and metastasis, but promotes apoptosis. J Mol Histol. 2015; 47(1):69-80. DOI: 10.1007/s10735-015-9650-3. View

Anderson M . Update on Survival in Osteosarcoma. Orthop Clin North Am. 2015; 47(1):283-92. DOI: 10.1016/j.ocl.2015.08.022. View

Cheng Y, Yang X, Deng X, Zhang X, Li P, Tao J . MicroRNA-218 inhibits bladder cancer cell proliferation, migration, and invasion by targeting BMI-1. Tumour Biol. 2015; 36(10):8015-23. DOI: 10.1007/s13277-015-3532-x. View

Su Z, Yang Z, Xu Y, Chen Y, Yu Q . MicroRNAs in apoptosis, autophagy and necroptosis. Oncotarget. 2015; 6(11):8474-90. PMC: 4496162. DOI: 10.18632/oncotarget.3523. View

Tie J, Pan Y, Zhao L, Wu K, Liu J, Sun S . MiR-218 inhibits invasion and metastasis of gastric cancer by targeting the Robo1 receptor. PLoS Genet. 2010; 6(3):e1000879. PMC: 2837402. DOI: 10.1371/journal.pgen.1000879. View

Xia H, Yan Y, Hu M, Wang Y, Wang Y, Dai Y . MiR-218 sensitizes glioma cells to apoptosis and inhibits tumorigenicity by regulating ECOP-mediated suppression of NF-κB activity. Neuro Oncol. 2012; 15(4):413-22. PMC: 3607258. DOI: 10.1093/neuonc/nos296. View

Uesugi A, Kozaki K, Tsuruta T, Furuta M, Morita K, Imoto I . The tumor suppressive microRNA miR-218 targets the mTOR component Rictor and inhibits AKT phosphorylation in oral cancer. Cancer Res. 2011; 71(17):5765-78. DOI: 10.1158/0008-5472.CAN-11-0368. View

10.

Yu H, Gao G, Jiang L, Guo L, Lin M, Jiao X . Decreased expression of miR-218 is associated with poor prognosis in patients with colorectal cancer. Int J Clin Exp Pathol. 2013; 6(12):2904-11. PMC: 3843271. View

11.

Wu D, Cheng Y, Wang J, Chen C, Lee H . Paxillin predicts survival and relapse in non-small cell lung cancer by microRNA-218 targeting. Cancer Res. 2010; 70(24):10392-401. DOI: 10.1158/0008-5472.CAN-10-2341. View

12.

Volinia S, Galasso M, Sana M, Wise T, Palatini J, Huebner K . Breast cancer signatures for invasiveness and prognosis defined by deep sequencing of microRNA. Proc Natl Acad Sci U S A. 2012; 109(8):3024-9. PMC: 3286983. DOI: 10.1073/pnas.1200010109. View

13.

Wang X, Lai P, Zhang Z, Huang M, Wang L, Yin M . Targeted inhibition of mTORC2 prevents osteosarcoma cell migration and promotes apoptosis. Oncol Rep. 2014; 32(1):382-8. DOI: 10.3892/or.2014.3182. View

14.

Zhang T, Zou P, Wang T, Xiang J, Cheng J, Chen D . Down-regulation of miR-320 associated with cancer progression and cell apoptosis via targeting Mcl-1 in cervical cancer. Tumour Biol. 2016; 37(7):8931-40. DOI: 10.1007/s13277-015-4771-6. View

15.

Dong R, Qiu H, Du G, Wang Y, Yu J, Mao C . Restoration of microRNA‑218 increases cellular chemosensitivity to cervical cancer by inhibiting cell‑cycle progression. Mol Med Rep. 2014; 10(6):3289-95. DOI: 10.3892/mmr.2014.2622. View

16.

Yang M, Liu R, Sheng J, Liao J, Wang Y, Pan E . Differential expression profiles of microRNAs as potential biomarkers for the early diagnosis of esophageal squamous cell carcinoma. Oncol Rep. 2012; 29(1):169-76. DOI: 10.3892/or.2012.2105. View

17.

Nishikawa R, Goto Y, Sakamoto S, Chiyomaru T, Enokida H, Kojima S . Tumor-suppressive microRNA-218 inhibits cancer cell migration and invasion via targeting of LASP1 in prostate cancer. Cancer Sci. 2014; 105(7):802-11. PMC: 4317931. DOI: 10.1111/cas.12441. View

18.

Alajez N, Lenarduzzi M, Ito E, Hui A, Shi W, Bruce J . MiR-218 suppresses nasopharyngeal cancer progression through downregulation of survivin and the SLIT2-ROBO1 pathway. Cancer Res. 2011; 71(6):2381-91. DOI: 10.1158/0008-5472.CAN-10-2754. View

19.

Tu Y, Gao X, Li G, Fu H, Cui D, Liu H . MicroRNA-218 inhibits glioma invasion, migration, proliferation, and cancer stem-like cell self-renewal by targeting the polycomb group gene Bmi1. Cancer Res. 2013; 73(19):6046-55. DOI: 10.1158/0008-5472.CAN-13-0358. View

20.

White N, Bao T, Grigull J, Youssef Y, Girgis A, Diamandis M . miRNA profiling for clear cell renal cell carcinoma: biomarker discovery and identification of potential controls and consequences of miRNA dysregulation. J Urol. 2011; 186(3):1077-83. DOI: 10.1016/j.juro.2011.04.110. View