Department of Nursing, Shanghai Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Department of General Surgery, Shanghai Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Cell Cycle. 2022 May;21(9):908-920. doi: 10.1080/15384101.2022.2034254. Epub 2022 Feb 3.
This study aimed to explore the role and potential mechanism of the long non-coding (lncRNA) MBNL1-AS1 in human breast cancer. We included 80 patients with breast cancer in this study. Breast cancer cell lines, including MCF7, SKBR3, MDA-MB-231 and MDA-MB-415, and the normal human breast cell line MCF10A were used in this study. MBNL1-AS1, miR-889-3p mimics, si-Krüppel-like factor 9 (KLF9) or their controls were transfected in the cells. Quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry assay were performed to detect the expression of MBNL1-AS1, miR-889-3p and KLF9. Cell proliferation, invasion and migration were detected. Luciferase reporter gene and pull-down assay were performed to verify the target relationship among MBNL1-AS1, miR-889-3p and KLF9. Glycolysis was also detected after transfection. The expression of the lncRNA MBNL1-AS1 was low in the breast cancer tissues and cells. Lower expression levels of the lncRNA MBNL1-AS1 were associated with poor prognosis of breast cancer. Overexpression of the lncRNA MBNL1-AS1 decreased proliferation, invasion, migration and glycolysis of breast cancer cells. The lncRNA MBNL1-AS1 could interact with miR-889-3p, and KLF9 was the downstream target of miR-889-3p. Moreover, miR-889-3p was negatively correlated with KLF9 and lncRNA MBNL1-AS1. Both miR-889-3p and si-KLF9 could reverse the overexpression of lncRNA MBNL1-AS1 in breast cancer development. The lncRNA MBNL1-AS1 decreased proliferation, invasion, migration and glycolysis of breast cancer via the miR-889-3p/KLF9 axis, which might be a potential biomarker for the diagnosis of breast cancer.
本研究旨在探讨长链非编码 RNA（lncRNA）MBNL1-AS1 在人乳腺癌中的作用及潜在机制。本研究纳入 80 例乳腺癌患者。本研究使用乳腺癌细胞系 MCF7、SKBR3、MDA-MB-231 和 MDA-MB-415 以及正常人类乳腺细胞系 MCF10A。细胞中转染 MBNL1-AS1、miR-889-3p 模拟物、si-Krüppel 样因子 9（KLF9）或其对照物。采用定量逆转录聚合酶链反应（qRT-PCR）、Western blot 及免疫组织化学检测 MBNL1-AS1、miR-889-3p 和 KLF9 的表达。检测细胞增殖、侵袭和迁移。进行荧光素酶报告基因和下拉检测以验证 MBNL1-AS1、miR-889-3p 和 KLF9 之间的靶标关系。转染后还检测了糖酵解。乳腺癌组织和细胞中 lncRNA MBNL1-AS1 的表达较低。lncRNA MBNL1-AS1 表达较低与乳腺癌的不良预后相关。lncRNA MBNL1-AS1 的过表达可降低乳腺癌细胞的增殖、侵袭、迁移和糖酵解。lncRNA MBNL1-AS1 可与 miR-889-3p 相互作用，KLF9 是 miR-889-3p 的下游靶标。此外，miR-889-3p 与 KLF9 和 lncRNA MBNL1-AS1 呈负相关。miR-889-3p 和 si-KLF9 均可逆转乳腺癌中 lncRNA MBNL1-AS1 的过表达。lncRNA MBNL1-AS1 通过 miR-889-3p/KLF9 轴降低乳腺癌的增殖、侵袭、迁移和糖酵解，可能是乳腺癌诊断的潜在生物标志物。
