Abstract
Background
The heterogeneity of breast tumors presents a challenge in disease management, necessitating an understanding of the molecular mechanisms driving breast tumorigenesis. Aberrant expression of microRNAs is known to promote tumor growth and progression. Our previous RNA-sequencing dataset revealed the upregulation of miR-362-5p and miR-454-3p in breast tumors. We investigated potential role of miR-362-5p and miR-454-3p in breast cancer using MDAMB231 and MCF7 cell lines.
Methods and results
The expression of miR-362-5p and miR-454-3p were altered in MCF7 and MDAMB231 using mimics and inhibitors. The effect on cell viability, cell cycle progression and migration was assessed using Alamar blue assay, flow cytometry and wound healing assay. Further, the expression of potential target genes were measured using real-time PCR. Our results indicated that an increased expression of miR-362-5p promoted cell growth and survival in MCF7, but decreased cell migration. In contrast, miR-362-5p overexpression reduced cancer cell growth, survival and migration in MDAMB231. Overexpression of miR-454-3p was oncogenic in both cell lines but suppressed migration in the aggressive cell line MDAMB231.
Conclusion
Two microRNAs, miR-362-5p and miR-454-3p, were evaluated for functional activity in breast cancer cell lines and they showed increased proliferative signals and tumorigenic properties.
This is a preview of subscription content, log in via an institution to check access.
Data availability
Data will be made available on request.
References
Bray F, Ferlay J, Soerjomataram I et al (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424. https://doi.org/10.3322/caac.21492
Ellsworth RE, Blackburn HL, Shriver CD et al (2017) Molecular heterogeneity in breast cancer: state of the science and implications for patient care. Semin Cell Dev Biol 64:65–72. https://doi.org/10.1016/j.semcdb.2016.08.025
Peng Y, Croce CM (2016) The role of MicroRNAs in human cancer. Signal Transduct Target Ther 1:15004. https://doi.org/10.1038/sigtrans.2015.4
Rao AKDM, Arvinden VR, Ramasamy D et al (2021) Identification of novel dysregulated circular RNAs in early-stage breast cancer. J Cell Mol Med 25:3912–3921. https://doi.org/10.1111/jcmm.16324
Ni F, Zhao H, Cui H et al (2014) MicroRNA-362-5p promotes tumor growth and metastasis by targeting CYLD in hepatocellular carcinoma. Cancer Lett 356:809–818. https://doi.org/10.1016/j.canlet.2014.10.041
Zhang X, He Q, Sun L et al (2019) Comparing MicroRNA profilings of purified HER-2-negative and HER-2-positive cells validates miR-362-5p/Sema3A as characteristic molecular change in triple-negative breast cancers. Dis Markers 2019:6057280. https://doi.org/10.1155/2019/6057280
Ren L, Chen H, Song J et al (2019) MiR-454-3p-mediated Wnt/β-catenin signaling antagonists suppression promotes breast cancer metastasis. Theranostics 9:449–465. https://doi.org/10.7150/thno.29055
Li Q, Liu J, Meng X et al (2017) MicroRNA-454 may function as an oncogene via targeting AKT in triple negative breast cancer. J Biol Res (Thessalon) 24:10. https://doi.org/10.1186/s40709-017-0067-x
Chandrashekar DS, Bashel B, Balasubramanya SAH et al (2017) UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia 19:649–658. https://doi.org/10.1016/j.neo.2017.05.002
Suarez-Arnedo A, Torres Figueroa F, Clavijo C et al (2020) An image J plugin for the high throughput image analysis of in vitro scratch wound healing assays. PLoS ONE 15:e0232565. https://doi.org/10.1371/journal.pone.0232565
Xie S, Zhu Q, Qu W et al (2019) sRNAPrimerDB: comprehensive primer design and search web service for small non-coding RNAs. Bioinformatics 35:1566–1572. https://doi.org/10.1093/bioinformatics/bty852
Cao Z-G, Li J-J, Yao L et al (2016) High expression of microRNA-454 is associated with poor prognosis in triple-negative breast cancer. Oncotarget 7:64900–64909. https://doi.org/10.18632/oncotarget.11764
Smith SE, Mellor P, Ward AK et al (2017) Molecular characterization of breast cancer cell lines through multiple omic approaches. Breast Cancer Res 19:65. https://doi.org/10.1186/s13058-017-0855-0
Zhu Y, Sullivan LL, Nair SS et al (2006) Coregulation of estrogen receptor by ERBB4/HER4 establishes a growth-promoting autocrine signal in breast tumor cells. Cancer Res 66:7991–7998. https://doi.org/10.1158/0008-5472.CAN-05-4397
Li X, Hou L, Yin L, Zhao S (2020) LncRNA XIST interacts with miR-454 to inhibit cells proliferation, epithelial mesenchymal transition and induces apoptosis in triple-negative breast cancer. J Biosci 45:45
Acknowledgements
The authors thank Dr. Priya Ramanathan and Dr. Hemavathi Dhandapani for supporting with the FACS experiments.
Funding
This study was supported by Department of Biotechnology, Government of India [Grant No.: BT/PR8152/AGR/36/739/2013] and Cancer Institute (WIA), India.
Author information
Authors and Affiliations
Contributions
Experiments, data analysis and interpretation, and manuscript preparation: AR; Experiments, data analysis, and manuscript preparation: AKDMR; Data analysis and Manuscript preparation: KP and HG, Manuscript preparation: SV; Study Conceptualization: TR; Fund acquisition, Study conceptualization, Experiment design and planning, Result interpretation: SM.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Aarthy, R., Rao, A.K.D.M., Patel, K. et al. Alteration of miR-362-5p and miR-454-3p expression elicits diverse responses in breast cancer cell lines. Mol Biol Rep 49, 821–826 (2022). https://doi.org/10.1007/s11033-021-06873-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11033-021-06873-1