Department of Clinical Biochemistry, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Department of Molecular Biology and Genetics, Gene Expression and Gene Medicine, Aarhus University, Aarhus, Denmark; Interdisciplinary Nanoscience Center, Aarhus University, Aarhus, Denmark.
Mol Cell Probes. 2020 Oct;53:101649. doi: 10.1016/j.mcp.2020.101649. Epub 2020 Aug 8.
Breast cancer is a type of cancer with a high incidence and mortality rate worldwide. Change in epigenetic mechanisms enhances cancer cell progression. Histon deacetylase 2 (HDAC2) was found to act as a potential oncogene in different malignancies. For better understanding the mechanisms related to breast cancer development, we investigated the role of HDAC2 in breast cancer and the inhibitory effect of miR-646 on this oncogene.
A total of thirty cancerous tissues and 30 adjacent non-cancerous specimens and also three breast cancer cell lines were enrolled in the study. Quantitative reverse transcriptase PCR (qRT-PCR) was employed to detect the HDAC2 and miR-646 expression level in the studied samples. The biological roles of HDAC2 and miR-646 were investigated through manipulating the expression level of HDAC2 or miR-646 in breast cancer cells. Finally, we evaluated whether the HDAC2 is a direct target for miR-646.
In this study, we found HDAC2 is significantly upregulated in cancerous specimens and cell lines compared to non-cancerous tissues and normal cell line. On the other hand, miR-646 expression was decreased in clinical specimens and breast cancer cells compared to non-cancerous samples. Knocking out of the HDAC2 and overexpression of miR-646 inhibited breast cancer cell growth but promoted cell death, while untreated groups showed inverse results. Furthermore, we showed that in the breast cancer cells, miR-646 regulates the progression and proliferation by suppressing HDAC2.
Taken together, our study identified a miR-646/HDAC2 regulatory function in the breast cancer development and introduced a therapeutically target for breast cancer.
乳腺癌是一种全球发病率和死亡率都很高的癌症。表观遗传机制的改变促进了癌细胞的进展。组蛋白去乙酰化酶 2（HDAC2）已被发现在不同的恶性肿瘤中作为潜在的癌基因发挥作用。为了更好地了解与乳腺癌发展相关的机制，我们研究了 HDAC2 在乳腺癌中的作用以及 miR-646 对这种癌基因的抑制作用。
本研究共纳入 30 例癌组织和 30 例相邻非癌组织，以及 3 种乳腺癌细胞系。采用定量逆转录聚合酶链反应（qRT-PCR）检测研究样本中 HDAC2 和 miR-646 的表达水平。通过操纵乳腺癌细胞中 HDAC2 或 miR-646 的表达水平来研究 HDAC2 和 miR-646 的生物学作用。最后，我们评估了 HDAC2 是否是 miR-646 的直接靶标。
在本研究中，我们发现与非癌组织和正常细胞系相比，癌组织和细胞系中 HDAC2 的表达显著上调。另一方面，与非癌样本相比，临床标本和乳腺癌细胞中 miR-646 的表达降低。敲除 HDAC2 和过表达 miR-646 抑制乳腺癌细胞生长但促进细胞死亡，而未处理组则显示相反的结果。此外，我们表明在乳腺癌细胞中，miR-646 通过抑制 HDAC2 来调节肿瘤的进展和增殖。
综上所述，我们的研究鉴定了 miR-646/HDAC2 在乳腺癌发展中的调节功能，并为乳腺癌提供了一个治疗靶标。
