Nanoliposomal Delivery of MicroRNA-203 Suppresses Migration of Triple-Negative Breast Cancer Through Distinct Target Suppression

Overview

Journal Noncoding RNA

Date 2021 Aug 27

PMID 34449670

Citations 2

Authors

Shuxuan Song

Kelsey S Johnson

Henry Lujan

Sahar H Pradhan

Christie M Sayes

Joseph H Taube

Affiliations

Soon will be listed here.

Abstract

Triple-negative breast cancers affect thousands of women in the United States and disproportionately drive mortality from breast cancer. MicroRNAs are small, non-coding RNAs that negatively regulate gene expression post-transcriptionally by inhibiting target mRNA translation or by promoting mRNA degradation. We have identified that miRNA-203, silenced by epithelial-mesenchymal transition (EMT), is a tumor suppressor and can promote differentiation of breast cancer stem cells. In this study, we tested the ability of liposomal delivery of miR-203 to reverse aspects of breast cancer pathogenesis using breast cancer and EMT cell lines. We show that translationally relevant methods for increasing miR-203 abundance within a target tissue affects cellular properties associated with cancer progression. While stable miR-203 expression suppresses LASP1 and survivin, nanoliposomal delivery suppresses BMI1, indicating that suppression of distinct mRNA target profiles can lead to loss of cancer cell migration.

Citing Articles

MEF2C and miR-194-5p: New Players in Triple Negative Breast Cancer Tumorigenesis.

Caetano S, Garcia A, Figueira I, Brito M Int J Mol Sci. 2023; 24(18).

PMID: 37762600 PMC: 10531597. DOI: 10.3390/ijms241814297.

Expression and Regulatory Mechanisms of MicroRNA in Cholesteatoma: A Systematic Review.

Dzaman K, Czerwaty K, Reichert T, Szczepanski M, Ludwig N Int J Mol Sci. 2023; 24(15).

PMID: 37569652 PMC: 10418341. DOI: 10.3390/ijms241512277.

References

Chim C, Wong K, Leung C, Chung L, Hui P, Chan S . Epigenetic inactivation of the hsa-miR-203 in haematological malignancies. J Cell Mol Med. 2011; 15(12):2760-7. PMC: 4373446. DOI: 10.1111/j.1582-4934.2011.01274.x. View

Zaravinos A . The Regulatory Role of MicroRNAs in EMT and Cancer. J Oncol. 2015; 2015:865816. PMC: 4389820. DOI: 10.1155/2015/865816. View

Wang N, Liang H, Zhou Y, Wang C, Zhang S, Pan Y . miR-203 suppresses the proliferation and migration and promotes the apoptosis of lung cancer cells by targeting SRC. PLoS One. 2014; 9(8):e105570. PMC: 4139332. DOI: 10.1371/journal.pone.0105570. View

Wang H, Jiang Y, Peng H, Chen Y, Zhu P, Huang Y . Recent progress in microRNA delivery for cancer therapy by non-viral synthetic vectors. Adv Drug Deliv Rev. 2014; 81:142-60. DOI: 10.1016/j.addr.2014.10.031. View

Yang D, Liu G, Wang K . miR-203 Acts as a Tumor Suppressor Gene in Osteosarcoma by Regulating RAB22A. PLoS One. 2015; 10(9):e0132225. PMC: 4575138. DOI: 10.1371/journal.pone.0132225. View

Burk U, Schubert J, Wellner U, Schmalhofer O, Vincan E, Spaderna S . A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Rep. 2008; 9(6):582-9. PMC: 2396950. DOI: 10.1038/embor.2008.74. View

Huang Y, Kuo C, Chen J, Goodfellow P, Huang T, Rader J . Hypermethylation of miR-203 in endometrial carcinomas. Gynecol Oncol. 2014; 133(2):340-5. PMC: 4015135. DOI: 10.1016/j.ygyno.2014.02.009. View

Bartel D . MicroRNAs: target recognition and regulatory functions. Cell. 2009; 136(2):215-33. PMC: 3794896. DOI: 10.1016/j.cell.2009.01.002. View

Ge X, Li G, Jiang L, Jia L, Zhang Z, Li X . Long noncoding RNA CAR10 promotes lung adenocarcinoma metastasis via miR-203/30/SNAI axis. Oncogene. 2019; 38(16):3061-3076. PMC: 6484688. DOI: 10.1038/s41388-018-0645-x. View

10.

Werden S, Sphyris N, Sarkar T, Paranjape A, LaBaff A, Taube J . Phosphorylation of serine 367 of FOXC2 by p38 regulates ZEB1 and breast cancer metastasis, without impacting primary tumor growth. Oncogene. 2016; 35(46):5977-5988. PMC: 5114155. DOI: 10.1038/onc.2016.203. View

11.

Di Leva G, Garofalo M, Croce C . MicroRNAs in cancer. Annu Rev Pathol. 2013; 9:287-314. PMC: 4009396. DOI: 10.1146/annurev-pathol-012513-104715. View

12.

Grimm D, Streetz K, Jopling C, Storm T, Pandey K, Davis C . Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature. 2006; 441(7092):537-41. DOI: 10.1038/nature04791. View

13.

Saini S, Majid S, Yamamura S, Tabatabai L, Suh S, Shahryari V . Regulatory Role of mir-203 in Prostate Cancer Progression and Metastasis. Clin Cancer Res. 2010; 17(16):5287-98. DOI: 10.1158/1078-0432.CCR-10-2619. View

14.

Garzon R, Marcucci G, Croce C . Targeting microRNAs in cancer: rationale, strategies and challenges. Nat Rev Drug Discov. 2010; 9(10):775-89. PMC: 3904431. DOI: 10.1038/nrd3179. View

15.

Xu Y, Lee D, Feng Z, Xu Y, Bu W, Li Y . Breast tumor cell-specific knockout of inhibits cancer cell plasticity, dissemination, and lung metastasis in mice. Proc Natl Acad Sci U S A. 2017; 114(43):11494-11499. PMC: 5664488. DOI: 10.1073/pnas.1618091114. View

16.

Prabhakar U, Maeda H, Jain R, Sevick-Muraca E, Zamboni W, Farokhzad O . Challenges and key considerations of the enhanced permeability and retention effect for nanomedicine drug delivery in oncology. Cancer Res. 2013; 73(8):2412-7. PMC: 3916009. DOI: 10.1158/0008-5472.CAN-12-4561. View

17.

Chang H, Yeh M . Clinical development of liposome-based drugs: formulation, characterization, and therapeutic efficacy. Int J Nanomedicine. 2012; 7:49-60. PMC: 3260950. DOI: 10.2147/IJN.S26766. View

18.

Comijn J, Berx G, Vermassen P, Verschueren K, van Grunsven L, Bruyneel E . The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Mol Cell. 2001; 7(6):1267-78. DOI: 10.1016/s1097-2765(01)00260-x. View

19.

Stenvang J, Petri A, Lindow M, Obad S, Kauppinen S . Inhibition of microRNA function by antimiR oligonucleotides. Silence. 2012; 3(1):1. PMC: 3306207. DOI: 10.1186/1758-907X-3-1. View

20.

Pareja F, Geyer F, Marchio C, Burke K, Weigelt B, Reis-Filho J . Triple-negative breast cancer: the importance of molecular and histologic subtyping, and recognition of low-grade variants. NPJ Breast Cancer. 2017; 2:16036. PMC: 5515338. DOI: 10.1038/npjbcancer.2016.36. View