MiR-34a-5p Promotes the Multi-drug Resistance of Osteosarcoma by Targeting the CD117 Gene

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Apr 9

PMID 27056900

Citations 30

Authors

Youguang Pu

Fangfang Zhao

Haiyan Wang

Wenjing Cai

Jin Gao

Yinpeng Li

Shanbao Cai

Affiliations

Soon will be listed here.

Abstract

An association has been reported between miR-34a-5p and several types of cancer. Specifically, in this study, using systematic observations of multi-drug sensitive (G-292 and MG63.2) and resistant (SJSA-1 and MNNG/HOS) osteosarcoma (OS) cell lines, we showed that miR-34a-5p promotes the multi-drug resistance of OS through the receptor tyrosine kinase CD117, a direct target of miR-34a-5p. Consistently, the siRNA-mediated repression of CD117 in G-292 and MG63.2 cells led to a similar phenotype that exhibited all of the miR-34a-5p mimic-triggered changes. In addition, the activity of the MEF2 signaling pathway was drastically altered by the forced changes in the miR-34a-5p or CD117 level in OS cells. Furthermore, si-CD117 suppressed the enhanced colony and sphere formation, which is in agreement with the characteristics of a cancer stem marker. Taken together, our data established CD117 as a direct target of miR-34-5p and demonstrated that this regulation interferes with several CD117-mediated effects on OS cells. In addition to providing new mechanistic insights, our results will provide an approach for diagnosing and chemotherapeutically treating OS.

Citing Articles

A New Functional Gene, Zinc Finger Protein 485 (ZNF485), is Involved in Bladder Cancer Proliferation.

Tan Y, Zhao F, Liu S, Huang T, Zang C, Sha D Bladder Cancer. 2024; 8(2):165-177.

PMID: 38993359 PMC: 11181812. DOI: 10.3233/BLC-211623.

Restoring microRNA-34a overcomes acquired drug resistance and disease progression in human breast cancer cell lines via suppressing the ABCC1 gene.

Yahya S, Nabih H, Elsayed G, Mohamed S, Elfiky A, Salem S Breast Cancer Res Treat. 2023; 204(1):133-149.

PMID: 38057687 PMC: 10806220. DOI: 10.1007/s10549-023-07170-0.

Non-coding RNAs in drug and radiation resistance of bone and soft-tissue sarcoma: a systematic review.

Chen H, Zhang T, Zhang F, Zhang T Elife. 2022; 11.

PMID: 36326232 PMC: 9691005. DOI: 10.7554/eLife.79655.

Chemoresistance-Related Stem Cell Signaling in Osteosarcoma and Its Plausible Contribution to Poor Therapeutic Response: A Discussion That Still Matters.

Martins-Neves S, Sampaio-Ribeiro G, Gomes C Int J Mol Sci. 2022; 23(19).

PMID: 36232719 PMC: 9569807. DOI: 10.3390/ijms231911416.

A miR-34a-guided, tRNA-derived, piR_019752-like fragment (tRiMetF31) suppresses migration and angiogenesis of breast cancer cells via targeting PFKFB3.

Wang B, Li D, Ilnytskyy Y, Kovalchuk I, Kovalchuk O Cell Death Discov. 2022; 8(1):355.

PMID: 35961977 PMC: 9374763. DOI: 10.1038/s41420-022-01054-w.

References

Gallardo E, Navarro A, Vinolas N, Marrades R, Diaz T, Gel B . miR-34a as a prognostic marker of relapse in surgically resected non-small-cell lung cancer. Carcinogenesis. 2009; 30(11):1903-9. DOI: 10.1093/carcin/bgp219. View

Ni S, Huang D, Chen X, Huang J, Kong Y, Xu Y . c-kit gene mutation and CD117 expression in human anorectal melanomas. Hum Pathol. 2011; 43(6):801-7. DOI: 10.1016/j.humpath.2011.08.005. View

Schetter A, Leung S, Sohn J, Zanetti K, Bowman E, Yanaihara N . MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA. 2008; 299(4):425-36. PMC: 2614237. DOI: 10.1001/jama.299.4.425. View

Deng H, Lv L, Li Y, Zhang C, Meng F, Pu Y . miR-193a-3p regulates the multi-drug resistance of bladder cancer by targeting the LOXL4 gene and the oxidative stress pathway. Mol Cancer. 2014; 13:234. PMC: 4200202. DOI: 10.1186/1476-4598-13-234. View

Kalathur R, Pinto J, Hernandez-Prieto M, Machado R, Almeida D, Chaurasia G . UniHI 7: an enhanced database for retrieval and interactive analysis of human molecular interaction networks. Nucleic Acids Res. 2013; 42(Database issue):D408-14. PMC: 3965034. DOI: 10.1093/nar/gkt1100. View

Botter S, Neri D, Fuchs B . Recent advances in osteosarcoma. Curr Opin Pharmacol. 2014; 16:15-23. DOI: 10.1016/j.coph.2014.02.002. View

Zhao H, Ma B, Wang Y, Han T, Zheng L, Sun C . miR-34a inhibits the metastasis of osteosarcoma cells by repressing the expression of CD44. Oncol Rep. 2013; 29(3):1027-36. DOI: 10.3892/or.2013.2234. View

Yamakuchi M, Lowenstein C . MiR-34, SIRT1 and p53: the feedback loop. Cell Cycle. 2009; 8(5):712-5. DOI: 10.4161/cc.8.5.7753. View

Montone K, van Belle P, Elenitsas R, Elder D . Proto-oncogene c-kit expression in malignant melanoma: protein loss with tumor progression. Mod Pathol. 1997; 10(9):939-44. View

10.

Pon J, Marra M . MEF2 transcription factors: developmental regulators and emerging cancer genes. Oncotarget. 2015; 7(3):2297-312. PMC: 4823036. DOI: 10.18632/oncotarget.6223. View

11.

Yang J, Zhang W . New molecular insights into osteosarcoma targeted therapy. Curr Opin Oncol. 2013; 25(4):398-406. DOI: 10.1097/CCO.0b013e3283622c1b. View

12.

Volinia S, Calin G, Liu C, Ambs S, Cimmino A, Petrocca F . A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A. 2006; 103(7):2257-61. PMC: 1413718. DOI: 10.1073/pnas.0510565103. View

13.

Anderson D, Lyman S, Baird A, Wignall J, Eisenman J, Rauch C . Molecular cloning of mast cell growth factor, a hematopoietin that is active in both membrane bound and soluble forms. Cell. 1990; 63(1):235-43. DOI: 10.1016/0092-8674(90)90304-w. View

14.

Lu J, Getz G, Miska E, Alvarez-Saavedra E, Lamb J, Peck D . MicroRNA expression profiles classify human cancers. Nature. 2005; 435(7043):834-8. DOI: 10.1038/nature03702. View

15.

Sattler M, Salgia R . Targeting c-Kit mutations: basic science to novel therapies. Leuk Res. 2004; 28 Suppl 1:S11-20. DOI: 10.1016/j.leukres.2003.10.004. View

16.

Song B, Wang Y, Xi Y, Kudo K, Bruheim S, Botchkina G . Mechanism of chemoresistance mediated by miR-140 in human osteosarcoma and colon cancer cells. Oncogene. 2009; 28(46):4065-74. PMC: 2783211. DOI: 10.1038/onc.2009.274. View

17.

He H, Ni J, Huang J . Molecular mechanisms of chemoresistance in osteosarcoma (Review). Oncol Lett. 2014; 7(5):1352-1362. PMC: 3997672. DOI: 10.3892/ol.2014.1935. View

18.

Li N, Fu H, Tie Y, Hu Z, Kong W, Wu Y . miR-34a inhibits migration and invasion by down-regulation of c-Met expression in human hepatocellular carcinoma cells. Cancer Lett. 2008; 275(1):44-53. DOI: 10.1016/j.canlet.2008.09.035. View

19.

Adhikari A, Agarwal N, Wood B, Porretta C, Ruiz B, Pochampally R . CD117 and Stro-1 identify osteosarcoma tumor-initiating cells associated with metastasis and drug resistance. Cancer Res. 2010; 70(11):4602-12. PMC: 3139225. DOI: 10.1158/0008-5472.CAN-09-3463. View

20.

Tarazona S, Garcia-Alcalde F, Dopazo J, Ferrer A, Conesa A . Differential expression in RNA-seq: a matter of depth. Genome Res. 2011; 21(12):2213-23. PMC: 3227109. DOI: 10.1101/gr.124321.111. View