MiR-577 Suppresses Epithelial-mesenchymal Transition and Metastasis of Breast Cancer by Targeting Rab25

Overview

Journal Thorac Cancer

Specialties Oncology
Pulmonary Medicine

Date 2018 Mar 11

PMID 29524309

Citations 29

Authors

Chonggao Yin

Qingjie Mou

Xinting Pan

Guoxin Zhang

Hongli Li

Yunbo Sun

Affiliations

Soon will be listed here.

Abstract

Background: MicroRNAs can act as both tumor suppressor genes and oncogenes and participate in cell proliferation, metastasis, and apoptosis. Low levels of miR-577 are found in several cancers, for example, thyroid carcinoma, glioblastoma, and hepatocellular carcinoma. The aim of this study was to investigate the effect of miR-577 on breast cancer (BC).

Methods: The relative level of miR-577 in 120 BC tissues and cells was detected by real-time PCR. MDA-MB-231 cells with upregulated miR-577 and MCF-7 cells with downregulated miR-577 were established. Transwell invasion assays were used to examine the invasiveness of cells. Epithelial-mesenchymal transition (EMT) markers were evaluated by immunofluorescence and Western blot. Targeted combinations of miR-577 and Rab25 were analyzed by luciferase assays. Xenograft models were used to examine the effect of miR-577 on BC metastasis.

Results: MiR-577 expression was significantly suppressed in BC tissues. Tumor size, tumor stage, and lymphatic metastasis were attributed to miR-577 expression. Moreover, miR-577 overexpression strongly inhibited the invasiveness and EMT of BC cells in vitro. MiR-577 directly regulated Rab25 in BC. Rab25 upregulation by miR-577 decreased the levels of E-cadherin and increased the levels of Vimentin. Notably, Rab25 knockdown inhibited BC invasion; however, an increase in Rab25 counteracted the invasive effect of miR-577 in BC.

Conclusion: Results indicated that miR-577 suppressed EMT by inhibiting Rab25 expression in BC. MiR-577 and Rab25 are considered potential targets of BC treatment.

Citing Articles

The potential mechanisms underlying phthalate-induced hypospadias: a systematic review of rodent model studies.

Zhang Y, Wang J, Yang H, Guan Y Front Endocrinol (Lausanne). 2024; 15:1490011.

PMID: 39698037 PMC: 11652206. DOI: 10.3389/fendo.2024.1490011.

Circ_0000376 regulates miR-577/HK2/LDHA signaling pathway to promote the growth, invasion and glycolysis of osteosarcoma.

Dai H, Yi G, Jiang D, Min Y, Li Z J Orthop Surg Res. 2024; 19(1):67.

PMID: 38218855 PMC: 10788008. DOI: 10.1186/s13018-023-04520-y.

miRSCAPE - inferring miRNA expression from scRNA-seq data.

Olgun G, Gopalan V, Hannenhalli S iScience. 2022; 25(9):104962.

PMID: 36060076 PMC: 9437856. DOI: 10.1016/j.isci.2022.104962.

Long noncoding RNA regulatory factor X3- antisense RNA 1 promotes non-small cell lung cancer via the microRNA-577/signal transducer and activator of transcription 3 axis.

Hu Y, Zhao Z, Jin G, Guo J, Nan F, Hu X Bioengineered. 2022; 13(4):10749-10764.

PMID: 35475457 PMC: 9208461. DOI: 10.1080/21655979.2022.2054910.

Integrative analysis of TCGA data identifies miRNAs as drug-specific survival biomarkers.

Lin S, Zhou J, Xiao Y, Neary B, Teng Y, Qiu P Sci Rep. 2022; 12(1):6785.

PMID: 35474090 PMC: 9042876. DOI: 10.1038/s41598-022-10662-6.

References

Sun L, Zhang B, Liu Y, Shi L, Li H, Lu S . MiR125a-5p acting as a novel Gab2 suppressor inhibits invasion of glioma. Mol Carcinog. 2015; 55(1):40-51. DOI: 10.1002/mc.22256. View

Tang C, Zhou H, Qin J, Luo Y, Zhang T . MicroRNA-520c-3p negatively regulates EMT by targeting IL-8 to suppress the invasion and migration of breast cancer. Oncol Rep. 2017; 38(5):3144-3152. DOI: 10.3892/or.2017.5968. View

Guarino M . Epithelial-mesenchymal transition and tumour invasion. Int J Biochem Cell Biol. 2007; 39(12):2153-60. DOI: 10.1016/j.biocel.2007.07.011. View

Wang L, Li B, Jiang H, Zhuang L, Liu Y . Inhibition effect of miR-577 on hepatocellular carcinoma cell growth via targeting β-catenin. Asian Pac J Trop Med. 2015; 8(11):923-929. DOI: 10.1016/j.apjtm.2015.10.001. View

Kalluri R, Weinberg R . The basics of epithelial-mesenchymal transition. J Clin Invest. 2009; 119(6):1420-8. PMC: 2689101. DOI: 10.1172/JCI39104. View

Lu Y, Qin T, Li J, Wang L, Zhang Q, Jiang Z . MicroRNA-140-5p inhibits invasion and angiogenesis through targeting VEGF-A in breast cancer. Cancer Gene Ther. 2017; 24(9):386-392. PMC: 5668497. DOI: 10.1038/cgt.2017.30. View

Dong Y, Liu Y, Jiang A, Li R, Yin M, Wang Y . MicroRNA-335 suppresses the proliferation, migration, and invasion of breast cancer cells by targeting EphA4. Mol Cell Biochem. 2017; 439(1-2):95-104. DOI: 10.1007/s11010-017-3139-1. View

Cheng K, Agarwal R, Mitra S, Lee J, Carey M, Gray J . Rab25 increases cellular ATP and glycogen stores protecting cancer cells from bioenergetic stress. EMBO Mol Med. 2012; 4(2):125-41. PMC: 3306554. DOI: 10.1002/emmm.201100193. View

Ventura A, Jacks T . MicroRNAs and cancer: short RNAs go a long way. Cell. 2009; 136(4):586-91. PMC: 3910108. DOI: 10.1016/j.cell.2009.02.005. View

10.

McGuire S . World Cancer Report 2014. Geneva, Switzerland: World Health Organization, International Agency for Research on Cancer, WHO Press, 2015. Adv Nutr. 2016; 7(2):418-9. PMC: 4785485. DOI: 10.3945/an.116.012211. View

11.

Jiang H, Ju H, Zhang L, Lu H, Jie K . microRNA-577 suppresses tumor growth and enhances chemosensitivity in colorectal cancer. J Biochem Mol Toxicol. 2017; 31(6). DOI: 10.1002/jbt.21888. View

12.

Chen C . MicroRNAs as oncogenes and tumor suppressors. N Engl J Med. 2005; 353(17):1768-71. DOI: 10.1056/NEJMp058190. View

13.

Xue Y, Xu W, Zhao W, Wang W, Zhang D, Wu P . miR-381 inhibited breast cancer cells proliferation, epithelial-to-mesenchymal transition and metastasis by targeting CXCR4. Biomed Pharmacother. 2016; 86:426-433. DOI: 10.1016/j.biopha.2016.12.051. View

14.

Zhang T, Wan J, Liu J, Deng M . MiR-200c inhibits metastasis of breast tumor via the downregulation of Foxf2. Genet Mol Res. 2017; 16(3). DOI: 10.4238/gmr16038971. View

15.

Li W, Li G, Fan Z, Liu T . Tumor-suppressive microRNA-452 inhibits migration and invasion of breast cancer cells by directly targeting RAB11A. Oncol Lett. 2017; 14(2):2559-2565. PMC: 5530176. DOI: 10.3892/ol.2017.6426. View

16.

Zhang W, Shen C, Li C, Yang G, Liu H, Chen X . miR-577 inhibits glioblastoma tumor growth via the Wnt signaling pathway. Mol Carcinog. 2015; 55(5):575-85. DOI: 10.1002/mc.22304. View

17.

Calin G, Croce C . MicroRNA-cancer connection: the beginning of a new tale. Cancer Res. 2006; 66(15):7390-4. DOI: 10.1158/0008-5472.CAN-06-0800. View

18.

Iorio M, Croce C . microRNA involvement in human cancer. Carcinogenesis. 2012; 33(6):1126-33. PMC: 3514864. DOI: 10.1093/carcin/bgs140. View

19.

Pinder S, Ellis I . The diagnosis and management of pre-invasive breast disease: ductal carcinoma in situ (DCIS) and atypical ductal hyperplasia (ADH)--current definitions and classification. Breast Cancer Res. 2003; 5(5):254-7. PMC: 314427. DOI: 10.1186/bcr623. View

20.

Mitra S, Federico L, Zhao W, Dennison J, Sarkar T, Zhang F . Rab25 acts as an oncogene in luminal B breast cancer and is causally associated with Snail driven EMT. Oncotarget. 2016; 7(26):40252-40265. PMC: 5130006. DOI: 10.18632/oncotarget.9730. View