Correlation between Expression of hsa-miR-490-5p and NFAT5 in Peripheral Blood Mononuclear Cell Obtained from Breast Cancer Patients

Document Type : Research Article

Authors

1 Department of Biology, Qom Branch, Islamic Azad University, Qom, Iran

2 Department of Photo Healing and Regeneration, Medical Laser Research Center, Yara Institute, ACECR, Tehran, Iran

Abstract

Breast cancer is a complex genetic disease that has an average annual incidence of two million people and the second leading cause of death among women all over the world. Micro-RNAs are consistently reported to regulate gene expression in all cancers. The present study, the correlation between the expression of hsa-miR-490-5p and nuclear factor of activated T-cells 5 (NFAT5) in breast cancer were investigated. NFAT5 nuclear accumulation occurs regardless of Wnt/β-catenin activated signaling in a substantial portion of breast cancer. The analysis of prediction target and dual-luciferase reporter assays supported that hsa-miR-490-5p directly targeted NFAT5 and suppressed the expression of NFAT5. In a cross-sectional comparative study, peripheral blood samples were collected from 30 subjects with breast cancer and 30 healthy individuals as a control group. Total mRNA was extracted from peripheral blood mononuclear cells (PBMCs) and cDNA was synthesized to study the NFAT5 and hsa-miR-490-5p gene expression variations by real-time PCR. A significant decrease was observed in gene expression and sera concentration of NFAT5, hsa-miR-490-5p in PBMCs of breast cancer patients. The obtained results indicated that hsa-miR-490-5p acts as oncomir in serum by targeting NFAT5 direct (p<0.05). 

Keywords


Babaei E, Hosseinpour Feizi M A. 2018. Study of the expression of miR-4270 in plasma of patients with breast invasive ductal carcinoma. J Genet Resour 4: 85-89.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. 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.
Chen H, Yu Y, Rong S, Wang H. 2014. Evaluation of diagnostic accuracy of DNA methylation biomarkers for bladder cancer: a systematic review and meta-analysis. Biomarkers 19: 189-197.
Chen K, Zeng J, Tang K, Xiao H, Hu J, Huang C, Yao W, Yu G, Xiao W, Guan W. 2016. miR‐490‐5p suppresses tumourgrowthin renal cell carcinoma through targeting PIK3CA. Biol Cell 108: 41-50.
Chen M, O'Connor K L. 2005. Integrin α6β4 promotes expression of autotaxin/ENPP2 autocrine motility factor in breast carcinoma cells. Oncogene 24: 5125.
Dejmek J, Säfholm A, Nielsen C K, Andersson T, Leandersson K. 2006. Wnt-5a/Ca2+-induced NFAT activity is counteracted by Wnt-5a/Yes-Cdc42-casein kinase 1α signaling in human mammary epithelial cells. Mol Cell Bio 26: 6024-6036.
Foldynová-Trantírková S, Sekyrová P, Tmejová K, Brumovská E, Bernatík O, Blankenfeldt W, Krejčí P, Kozubík A, Doležal T, Trantírek L. 2010. Breast cancer-specific mutations in CK1ε inhibit Wnt/β-catenin and activate the Wnt/Rac1/JNK and NFAT pathways to decrease cell adhesion and promote cell migration. Breast Cancer Res 12: R30.
Hosseinzadeh Colagar A, Moradi Firouzjah H, Halalkhor S. 2015. Vitamin D receptor poly (A)-microsatellite polymorphism and serum levels of 25-hydroxyvitamin D: association with susceptibility to breast cancer. J Breast Cancer 18(2): 119-125.
JauliacS, López-Rodriguez C, Shaw LM, Brown LF, Rao A, Toker A. 2002. The role of NFAT transcription factors in integrin-mediated carcinoma invasion. Nat Cell Biol 4: 540.
López-Rodríguez C, Antos CL, Shelton JM, Richardson JA, Lin F, Novobrantseva TI, Bronson RT, Igarashi P, Rao A, Olson EN. 2004. Loss of NFAT5 results in renal atrophy and lack of tonicity-responsive gene expression. Proc Natl Acad Sci USA 101: 2392-2397.
Luo C, Shaw K, Raghavan A, Aramburu J, Garcia-Cozar F, Perrino BA, Hogan PG, Rao A. 1996. Interaction of calcineurin with a domain of the transcription factor NFAT1 that controls nuclear import. Proc Natl Acad Sci USA 93: 8907-8912.
Mu Y, Li N, Cui Y-L. 2018. The lncRNA CCAT1 upregulates TGFβR1 via sponging miR-490-3p to promote TGFβ1-induced EMT of ovarian cancer cells. Cancer Cell Int 18: 145.
Seifert A, Rau S, Küllertz G, Fischer B, Santos AN. 2009. TCDD induces cell migration via NFATc1/ATX-signaling in MCF-7 cells. Toxicol Let 184: 26-32.
Shimomura A, Shiino S, Kawauchi J, Takizawa S, Sakamoto H, Matsuzaki J, Ono M, Takeshita F, Niida S, and Shimizu C. 2016. Novelcombinationof serum microRNA for detecting breast cancer in the early stage. Cancer Sci 107: 326-334.
Siamakpour-Reihani S, Caster J, Nepal DB, Courtwright A, Hilliard E, Usary J, Ketelsen D, Darr D, Shen X J, Patterson C. 2011. The role of calcineurin/NFAT in SFRP2 induced angiogenesis—a rationale for breast cancer treatment with the calcineurin inhibitor tacrolimus. PLoS One 6: e20412.
Sun K.-X, Chen Y, Chen S, Liu B-L, Feng M-X, Zong Z-H, Zhao Y. 2016. The correlation between microRNA490-3p and TGFα in endometrial carcinoma tumorigenesis and progression. Oncotarget 7: 9236.
Tafrihi M, Hasheminasab E. 2019. MiRNAs: biology, biogenesis, their web-based tools, and databases. MicroRNA 8(1): 4-27.
Tian J, Xu Y.-Y, Li L, Hao Q. 2017. MiR-490-3p sensitizes ovarian cancer cells to cisplatin by directly targeting ABCC2. Am J Transl Res 9: 1127.
Wang D Y, GendooD.M, Ben-David Y, Woodgett J.R, Zacksenhaus E. 2019. A subgroup of microRNAs defines PTEN-deficient, triple-negative breast cancer patients with poorest prognosis and alterations in RB1, MYC, and Wnt signaling. Breast Cancer Res 21: 18.
Xu X, Chen R, Li Z, Huang N, Wu X, Li S, Li Y, Wu S. 2015. MicroRNA-490-3p inhibits colorectal cancer metastasis by targeting TGFβR1. BMC Cancer 15: 1023.
Yiu G K, Toker A. 2006. NFAT induces breast cancer cell invasion by promoting the induction of cyclooxygenase-2. J Biol Chem 281: 12210-12217.
Yoeli-Lerner M, Yiu G K, Rabinovitz I, Erhardt P, Jauliac S, Toker A. 2005. Akt blocks breast cancer cell motility and invasion through the transcription factor NFAT. Mol Cell 20: 539-550.
Yoeli-Lerner M, Chin Y R, Hansen C K, Toker A. 2009. Akt/protein kinase B and glycogen synthase kinase-3β signaling pathway regulatescellmigration through the NFAT1 transcription factor. Mol Cancer Res 7: 425-432.
Zhao L, Zheng XY. 2016. MicroRNA-490 inhibits tumorigenesis and progression in breast cancer. OncoTargets Ther 9: 4505.