Mobarra Naser, Shafiee Abbas, Rad Seyed Mohammad Ali Hosseini, Tasharrofi Nooshin, Soufi-Zomorod Mina, Hafizi Maryam, Movahed Marjan, Kouhkan Fatemeh, Soleimani Masoud
Department of Biochemistry, Metabolic Disorders Research Center, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
In Vitro Cell Dev Biol Anim. 2015 Jun;51(6):604-11. doi: 10.1007/s11626-015-9872-4. Epub 2015 Feb 12.
MicroRNAs (miRNA) are a large family of small single-stranded RNA molecules found in all multicellular organisms. Early studies have been shown that miRNA are involved in cancer development and progression, and this role can be done by working as an oncogenes and tumor suppressor genes, so manipulation of this molecules can be a promising approach in cancer therapy, and experimental results represented that the modification in breast cancer phenotype is possible by miRNA expression alteration. miR-16, which is located in 13q14 chromosome, plays critical roles as a tumor suppressor by targeting several oncogenes which regulate cell cycle and apoptosis. Hence, in the present study, we investigated whether miR-16 could decline growth and survival of MCF-7 cell line as model of human breast cancer. MCF-7 cell line was infected with lentiviruses containing miR-16 precursor sequence. The effects of ectopic expression of miR-16 on breast cancer phenotype were examined by cell cycle analysis and apoptosis assays. miR-16 cytotoxicity effect was measured by the MTT assay. We showed that the miR-16 overexpression reduces Cyclin D1 and BCL2 at messenger RNA (mRNA) and protein levels in MCF-7 cell line. In addition, this is found that enforced expression of miR-16 decreases cell growth and proliferation and induces apoptosis in MCF-7 cells. In conclusion, our results revealed that upregulation of miR-16 would be a potential approach for breast cancer therapy.
微小RNA（miRNA）是在所有多细胞生物中发现的一大类小单链RNA分子。早期研究表明，miRNA参与癌症的发生和发展，其作用可通过作为癌基因和肿瘤抑制基因来实现，因此对这类分子的操控可能是癌症治疗中一种有前景的方法，实验结果表明通过改变miRNA表达有可能改变乳腺癌表型。位于13q14染色体上的miR-16，通过靶向调控细胞周期和凋亡的多个癌基因发挥关键的肿瘤抑制作用。因此，在本研究中，我们调查了miR-16是否能降低作为人乳腺癌模型的MCF-7细胞系的生长和存活率。MCF-7细胞系用含有miR-16前体序列的慢病毒进行感染。通过细胞周期分析和凋亡检测来检查miR-16异位表达对乳腺癌表型的影响。用MTT法测定miR-16的细胞毒性作用。我们发现，miR-16过表达在MCF-7细胞系的信使核糖核酸（mRNA）和蛋白质水平上降低细胞周期蛋白D1和BCL2。此外，还发现miR-16的强制表达会降低MCF-7细胞的生长和增殖并诱导其凋亡。总之，我们的结果表明，上调miR-16可能是乳腺癌治疗的一种潜在方法。
