Liu Heng, Wang Gangyue
Department of Breast Surgery, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100006, P.R. China.
Exp Ther Med. 2021 Sep;22(3):945. doi: 10.3892/etm.2021.10377. Epub 2021 Jul 1.
Breast cancer is one of the most frequently diagnosed malignancies among women. Triple-negative breast cancer (TNBC) represents a significant challenge for breast oncologists, as the availability of effective therapies for this aggressive disease is limited. The molecular mechanisms underlying TNBC development are not fully understood. Previous studies have demonstrated that microRNAs (miRNAs/miRs) play important roles in the development of various types of cancer, including breast cancer; however, the role of miRNAs in TNBC remains undetermined. The results of the present study revealed that miR-301a-3p may function as an oncogenic miRNA in TNBC. Based on The Cancer Genome Atlas data, miR-301a-3p expression levels were found to be upregulated in breast cancer tissues. Reverse transcription-quantitative PCR analysis demonstrated that the expression levels of miR-301a-3p were upregulated in TNBC tissues compared with non-TNBC tissues, and in MDA-MB-231 cells compared with normal MCF-10A breast cells. miR-301a-3p mimics and inhibitors were subsequently used to overexpress and knock down miR-301a-3p expression, respectively, in MDA-MB-231 cells. Biological functional experiments demonstrated that miR-301a-3p overexpression increased the viability, and the migratory and invasive abilities of MDA-MB-231 cells. By contrast, miR-301a-3p knockdown exerted the opposite effects on MDA-MB-231 cells. Cell apoptosis was negatively regulated by miR-301a-3p. Moreover, overexpression of miR-301a-3p was found to downregulate the expression levels of mesenchyme homeobox 2 (MEOX2). The expression levels of miR-301a-3p were negatively correlated with the expression levels of MEOX2 in clinical tissue specimens from patients with TNBC. Subsequently, the knockdown of MEOX2 expression promoted the viability of MDA-MB-231 cells. In conclusion, the results of the present study suggested that miR-301a-3p may serve as an oncogenic miRNA in TNBC by regulating MEOX2 expression.
乳腺癌是女性中最常被诊断出的恶性肿瘤之一。三阴性乳腺癌（TNBC）对乳腺肿瘤学家来说是一项重大挑战，因为针对这种侵袭性疾病的有效治疗方法有限。TNBC发生发展的分子机制尚未完全明确。以往研究表明，微小RNA（miRNA/miR）在包括乳腺癌在内的各种癌症发生发展中发挥重要作用；然而，miRNA在TNBC中的作用仍未确定。本研究结果显示，miR - 301a - 3p在TNBC中可能作为一种致癌性miRNA发挥作用。基于癌症基因组图谱数据，发现miR - 301a - 3p在乳腺癌组织中表达上调。逆转录定量PCR分析表明，与非TNBC组织相比，TNBC组织中miR - 301a - 3p的表达水平上调，与正常MCF - 10A乳腺细胞相比，MDA - MB - 231细胞中miR - 301a - 3p的表达水平上调。随后，分别使用miR - 301a - 3p模拟物和抑制剂在MDA - MB - 231细胞中过表达和敲低miR - 301a - 3p的表达。生物学功能实验表明，miR - 301a - 3p过表达增加了MDA - MB - 231细胞的活力、迁移和侵袭能力。相比之下，miR - 301a - 3p敲低对MDA - MB - 231细胞产生相反的影响。细胞凋亡受到miR - 301a - 3p的负调控。此外，发现miR - 301a - 3p过表达下调间充质同源框2（MEOX2）的表达水平。在TNBC患者的临床组织标本中，miR - 301a - 3p的表达水平与MEOX2的表达水平呈负相关。随后，MEOX2表达的敲低促进了MDA - MB - 231细胞的活力。总之，本研究结果表明，miR - 301a - 3p可能通过调节MEOX2表达在TNBC中作为致癌性miRNA发挥作用。
