文章：

miR-622通过抑制缺氧诱导因子1α上调miR-30a表达改善人侵袭性乳腺癌细胞的转移与化疗耐药性

miR-622 Increases miR-30a Expression through Inhibition of Hypoxia-Inducible Factor 1α to Improve Metastasis and Chemoresistance in Human Invasive Breast Cancer Cells

原文发布日期：3 February 2024

DOI: 10.3390/cancers16030657

类型: Article

开放获取: 是

英文摘要：

Hypoxia-inducible factor 1α (HIF-1α) plays a pivotal role in the survival, metastasis, and response to treatment of solid tumors. Autophagy serves as a mechanism for tumor cells to eliminate misfolded proteins and damaged organelles, thus promoting invasiveness, metastasis, and resistance to treatment under hypoxic conditions. MicroRNA (miRNA) research underscores the significance of these non-coding molecules in regulating cancer-related protein synthesis across diverse contexts. However, there is limited reporting on miRNA-mediated gene expression studies, especially with respect to epithelial–mesenchymal transition (EMT) and autophagy in the context of hypoxic breast cancer. Our study reveals decreased levels of miRNA-622 (miR-622) and miRNA-30a (miR-30a) in invasive breast cancer cells compared to their non-invasive counterparts. Inducing miR-622 suppresses HIF-1α protein expression, subsequently activating miR-30a transcription. This cascade results in reduced invasiveness and migration of breast cancer cells by inhibiting EMT markers, such as Snail, Slug, and vimentin. Furthermore, miR-30a negatively regulates beclin 1, ATG5, and LC3-II and inhibits Akt protein phosphorylation. Consequently, this improves the sensitivity of invasive MDA-MB-231 cells to docetaxel treatment. In conclusion, our study highlights the therapeutic potential of inducing miR-622 to promote miR-30a expression and thus disrupt HIF-1α-associated EMT and autophagy pathways. This innovative strategy presents a promising approach to the treatment of aggressive breast cancer.

摘要翻译： 

缺氧诱导因子1α（HIF-1α）在实体肿瘤的存活、转移及治疗反应中发挥关键作用。自噬作为肿瘤细胞清除错误折叠蛋白和受损细胞器的机制，在缺氧条件下可促进肿瘤侵袭、转移及治疗抵抗。MicroRNA（miRNA）研究揭示了这些非编码分子在不同背景下调控癌症相关蛋白合成的重要性。然而，目前关于miRNA介导的基因表达研究报道有限，特别是在缺氧性乳腺癌背景下与上皮-间质转化（EMT）及自噬相关的研究。本研究发现，与非侵袭性乳腺癌细胞相比，侵袭性乳腺癌细胞中miRNA-622（miR-622）和miRNA-30a（miR-30a）水平降低。诱导miR-622可抑制HIF-1α蛋白表达，进而激活miR-30a转录。这一级联反应通过抑制Snail、Slug和波形蛋白等EMT标志物，降低乳腺癌细胞的侵袭和迁移能力。此外，miR-30a负向调控beclin 1、ATG5和LC3-II，并抑制Akt蛋白磷酸化，从而增强侵袭性MDA-MB-231细胞对多西他赛治疗的敏感性。综上所述，本研究揭示了诱导miR-622以促进miR-30a表达、进而破坏HIF-1α相关EMT和自噬通路的治疗潜力，为侵袭性乳腺癌的治疗提供了创新策略。

原文链接：

miR-622 Increases miR-30a Expression through Inhibition of Hypoxia-Inducible Factor 1α to Improve Metastasis and Chemoresistance in Human Invasive Breast Cancer Cells