Evaluation of in Vivo Antitumor Effects of Low-frequency Ultrasound-mediated MiRNA-133a Microbubble Delivery in Breast Cancer

Overview

Journal Cancer Med

Specialty Oncology

Date 2016 Jul 29

PMID 27465833

Citations 28

Authors

Yanlei Ji

Zhen Han

LiMei Shao

Yuehuan Zhao

Affiliations

Soon will be listed here.

Abstract

MicroRNAs (miRNAs), as a novel class of small noncoding RNAs, have been identified as important transcriptional and posttranscriptional inhibitors of gene expression. Ultrasound-targeted microbubble destruction (UTMD) is a noninvasive method for microRNA delivery. We aimed to investigate the effect of UTMD of miR-133a on breast cancer treatment. It has been reported that miRNA-133a is involved in various cancers. miR-133a was lowly expressed in breast cancer tissues and breast cancer cell lines MCF-7 and MDA-MB-231. The miR-133a expression was significantly upregulated under exogenous miRNA-133a treatment in MCF-7 and MDA-MB-231 cells analyzed by qRT-PCR. Exogenous miR-133a promoted the cell proliferation as determined by diphenyl tetrazolium bromide (MTT) assay and 5-ethynyl-2'-deoxyuridine (EdU) staining. Epidermal growth factor receptor (EGFR) expression and Akt phosphorylation were significantly suppressed after miR-133a transfection by western blot detection. We prepared the miR-133a-microbubble and injected it into breast cancer xenografts. The miR-133a-microbubble injection prolonged miR-133a circulatory time by detecting the amount of miRNA-133a in the plasma. No significant toxicity was observed on alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at liver and albumin, blood urea nitrogen, or creatine kinase levels at kidney after miR-133a-microbubble injection. The tumor size of miR-133a-microbubble-injected mice was smaller than that of the control group. Furthermore, the delivery efficiency of miR-133a with low frequency was higher than that with common frequency. miR-133a suppressed cell proliferation by suppressing the expression of EGFR and the phosphorylation of Akt. UTMD of miR-133a inhibited the tumor growth and improved the survival rate in breast cancer mice. Our study provides new evidence that UTMD of miRNA is a promising platform for breast cancer therapy.

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References

Xu Q, Sun T, Tian H, Wang C, Zhou H . Ultrasound-mediated vascular endothelial growth factor C (VEGF-C) gene microbubble transfection inhibits growth of MCF-7 breast cancer cells. Oncol Res. 2013; 20(7):297-301. DOI: 10.3727/096504013x13639794277680. View

Hata A, Kashima R . Dysregulation of microRNA biogenesis machinery in cancer. Crit Rev Biochem Mol Biol. 2015; 51(3):121-34. PMC: 5226641. DOI: 10.3109/10409238.2015.1117054. View

Cui W, Zhang S, Shan C, Zhou L, Zhou Z . microRNA-133a regulates the cell cycle and proliferation of breast cancer cells by targeting epidermal growth factor receptor through the EGFR/Akt signaling pathway. FEBS J. 2013; 280(16):3962-74. DOI: 10.1111/febs.12398. View

Herbst R . Review of epidermal growth factor receptor biology. Int J Radiat Oncol Biol Phys. 2004; 59(2 Suppl):21-6. DOI: 10.1016/j.ijrobp.2003.11.041. View

Jemal A, Bray F, Center M, Ferlay J, Ward E, Forman D . Global cancer statistics. CA Cancer J Clin. 2011; 61(2):69-90. DOI: 10.3322/caac.20107. View

Nohata N, Hanazawa T, Kikkawa N, Mutallip M, Fujimura L, Yoshino H . Caveolin-1 mediates tumor cell migration and invasion and its regulation by miR-133a in head and neck squamous cell carcinoma. Int J Oncol. 2010; 38(1):209-17. View

Wu Z, Wang C, Xiang R, Liu X, Ye S, Yang X . Loss of miR-133a expression associated with poor survival of breast cancer and restoration of miR-133a expression inhibited breast cancer cell growth and invasion. BMC Cancer. 2012; 12:51. PMC: 3297527. DOI: 10.1186/1471-2407-12-51. View

Zhang L, Liu Y, Xiang G, Lv Q, Huang G, Yang Y . Ultrasound-triggered microbubble destruction in combination with cationic lipid microbubbles enhances gene delivery. J Huazhong Univ Sci Technolog Med Sci. 2011; 31(1):39-45. DOI: 10.1007/s11596-011-0147-3. View

Wang L, Hsiao T, Hong T, Chen H, Kao S, Wang W . MicroRNA-133a suppresses multiple oncogenic membrane receptors and cell invasion in non-small cell lung carcinoma. PLoS One. 2014; 9(5):e96765. PMC: 4016005. DOI: 10.1371/journal.pone.0096765. View

10.

Uchida Y, Chiyomaru T, Enokida H, Kawakami K, Tatarano S, Kawahara K . MiR-133a induces apoptosis through direct regulation of GSTP1 in bladder cancer cell lines. Urol Oncol. 2011; 31(1):115-23. DOI: 10.1016/j.urolonc.2010.09.017. View

11.

Taniyama Y, Tachibana K, Hiraoka K, Namba T, Yamasaki K, Hashiya N . Local delivery of plasmid DNA into rat carotid artery using ultrasound. Circulation. 2002; 105(10):1233-9. DOI: 10.1161/hc1002.105228. View

12.

Cui W, Zhang Y, Hu N, Shan C, Zhang S, Zhang W . miRNA-520b and miR-520e sensitize breast cancer cells to complement attack via directly targeting 3'UTR of CD46. Cancer Biol Ther. 2010; 10(3):232-41. DOI: 10.4161/cbt.10.3.12277. View

13.

Lam J, Chow M, Zhang Y, Leung S . siRNA Versus miRNA as Therapeutics for Gene Silencing. Mol Ther Nucleic Acids. 2015; 4:e252. PMC: 4877448. DOI: 10.1038/mtna.2015.23. View

14.

Ji Y, Han Z, Shao L, Zhao Y . Evaluation of in vivo antitumor effects of low-frequency ultrasound-mediated miRNA-133a microbubble delivery in breast cancer. Cancer Med. 2016; 5(9):2534-43. PMC: 5055178. DOI: 10.1002/cam4.840. View

15.

Cao W, Rosenblat J, Roth N, Kuliszewski M, Matkar P, Rudenko D . Therapeutic Angiogenesis by Ultrasound-Mediated MicroRNA-126-3p Delivery. Arterioscler Thromb Vasc Biol. 2015; 35(11):2401-11. DOI: 10.1161/ATVBAHA.115.306506. View

16.

Leong-Poi H, Kuliszewski M, Lekas M, Sibbald M, Teichert-Kuliszewska K, Klibanov A . Therapeutic arteriogenesis by ultrasound-mediated VEGF165 plasmid gene delivery to chronically ischemic skeletal muscle. Circ Res. 2007; 101(3):295-303. DOI: 10.1161/CIRCRESAHA.107.148676. View

17.

Phillips L, Klibanov A, Wamhoff B, Hossack J . Targeted gene transfection from microbubbles into vascular smooth muscle cells using focused, ultrasound-mediated delivery. Ultrasound Med Biol. 2010; 36(9):1470-80. PMC: 2930891. DOI: 10.1016/j.ultrasmedbio.2010.06.010. View

18.

Kim V . MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol. 2005; 6(5):376-85. DOI: 10.1038/nrm1644. View

19.

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

20.

Tan X, Xia F . Long-term fatigue state in postoperative patients with breast cancer. Chin J Cancer Res. 2014; 26(1):12-6. PMC: 3937751. DOI: 10.3978/j.issn.1000-9604.2014.01.12. View