Tehran University of Medical Sciences, School of Medicine, Department of Immunology - Tehran, Iran.
Tehran University of Medical Sciences, Children's Medical Center, Research Center for Immunodeficiencies - Tehran, Iran.
Rev Assoc Med Bras (1992). 2022 Apr;68(4):456-462. doi: 10.1590/1806-9282.20210966.
The phosphoinositide 3-kinase/protein kinase AKT/mammalian target of rapamycin signaling pathway is essential for proper cellular metabolism and cell growth. However, aberrant activation of this pathway has been linked to the progression and metastasis of breast cancer. Recently, the role of long non-coding RNAs in interfering with the cell signaling pathways involved in cell growth and metabolism has been identified. HOX antisense intergenic RNA is an long non-coding RNA whose abnormal expression has been associated with development, therapy resistance, and metastasis of breast cancer. The purpose of this study was to investigate whether the long non-coding RNA HOX antisense intergenic RNA is linked to the phosphoinositide 3-kinase/protein kinase AKT/mammalian target of rapamycin signaling pathway in breast cancer cells.
HOX antisense intergenic RNA was silenced in the breast cancer cell line MCF-7 using siRNAs. Subsequently, the gene expression level of HOX antisense intergenic RNA, PI3K, AKT, and mTOR was assessed using real-time RT-PCR. Also, the 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyl-tetrazolium bromide) assay was used to analyze cell proliferation.
The results revealed that HOX antisense intergenic RNA knockdown can downregulate the expression of PI3K, AKT, and mTOR RNAs compared to negative control in MCF-7 cells. In addition, the proliferation of breast cancer cells was significantly reduced following the HOX antisense intergenic RNA silencing.
This study may introduce HOX antisense intergenic RNA as a molecule involved in the upregulation of the phosphoinositide 3-kinase/protein kinase AKT/mammalian target of rapamycin signaling pathway in breast cancer cells that may contribute to breast cancer cell proliferation.
磷酸肌醇 3-激酶/蛋白激酶 AKT/雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR）信号通路对于细胞代谢和生长至关重要。然而，该通路的异常激活与乳腺癌的进展和转移有关。最近，长链非编码 RNA（long non-coding RNA，lncRNA）在干扰细胞生长和代谢相关细胞信号通路中的作用已被确定。HOX 反义基因间 RNA（HOX antisense intergenic RNA，HOTAIR）是一种 lncRNA，其异常表达与乳腺癌的发生、耐药和转移有关。本研究旨在探讨乳腺癌细胞中 lncRNA HOTAIR 是否与磷酸肌醇 3-激酶/蛋白激酶 AKT/mTOR 信号通路有关。
使用 siRNA 沉默乳腺癌细胞系 MCF-7 中的 HOTAIR。随后，使用实时 RT-PCR 评估 HOTAIR、PI3K、AKT 和 mTOR 的基因表达水平。此外，还使用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide，MTT）法分析细胞增殖。
结果显示，与阴性对照组相比，MCF-7 细胞中 HOTAIR 敲低可下调 PI3K、AKT 和 mTOR RNA 的表达。此外，沉默 HOTAIR 后乳腺癌细胞的增殖明显减少。
本研究可能将 HOTAIR 引入乳腺癌细胞中磷酸肌醇 3-激酶/蛋白激酶 AKT/mTOR 信号通路的上调机制中，这可能有助于乳腺癌细胞的增殖。
