Downregulation of miR-129-2 by promoter hypermethylation regulates breast cancer cell proliferation and apoptosis
Downregulation of miR-129-2 by promoter hypermethylation regulates breast cancer cell proliferation and apoptosis
复制标题
启动子高甲基化下调 miR-129-2 可调节乳腺癌细胞增殖和凋亡。
DOI：
10.3892/or.2016.4647
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发表时间：
2016-05-01
期刊：
影响因子：
4.2
通讯作者：
Lv, Xiao-Bin
中科院分区：
文献类型：
--
作者：
Tang, Xiaofeng;Tang, Jianjun;Lv, Xiao-Bin
miR-129家族的异常表达已在几种类型的癌症中发现，但其在乳腺癌中的表达和潜在的生物学作用在很大程度上仍然未知。在本研究中，我们发现miR-129-2在乳腺癌标本和细胞系中持续下调。过表达miR-129-2- 3 p可显著抑制乳腺癌细胞增殖并诱导其凋亡。此外，荧光素酶报告基因测定显示miR-129-2- 3 p抑制BCL 2L 2表达。此外，BCL 2L 2能够逆转miR-129-2- 3 p介导的细胞凋亡，表明BCL 2L 2在介导miR-129-2- 3 p的肿瘤抑制作用中起关键作用。此外，亚硫酸氢盐DNA测序PCR（BSP）分析表明，启动子甲基化是导致乳腺癌中miR-129-2下调的原因。总的来说，我们的研究结果表明，miR-129-2在乳腺癌细胞中通过启动子超甲基化下调。此外，miR-129-2的下调导致乳腺癌患者中BCL 2L 2过表达和疾病进展。
Aberrant expression of the miR-129 family has been found in several types of cancer, yet its expression and potential biologic role in breast cancer remain largely unknown. In the present study, we found that miR-129-2 was consistently downregulated in the breast cancer specimens and cell lines. Overexpression of miR-129-2-3p markedly suppressed breast cancer cell proliferation and induced its apoptosis. In addition, a luciferase reporter assay revealed that miR-129-2-3p suppressed BCL2L2 expression. Furthermore, BCL2L2 was able to reverse miR-129-2-3p-mediated cell apoptosis, indicating that BCL2L2 plays a crucial role in mediating the tumor-suppressive role of miR-129-2-3p. Moreover, bisulfite DNA sequencing PCR (BSP) analysis identified that promoter hypermethylation was responsible for the downregulation of miR-129-2 in breast cancer. Collectively, our findings indicate that miR-129-2 is downregulated in breast cancer cells by promoter hypermethylation. Moreover, downregulation of miR-129-2 results in BCL2L2 overexpression and disease progression in breast cancer patients.