LncRNA-BC069792通过针对KCNQ4抑制乳腺癌的肿瘤进展。
LncRNA-BC069792 suppresses tumor progression by targeting KCNQ4 in breast cancer.
发表日期:2023 Mar 01
作者:
Yunxiang Zhang, Xiaotong Dong, Xiangyu Guo, Chunsen Li, Yanping Fan, Pengju Liu, Dawei Yuan, Xialin Ma, Jingru Wang, Jie Zheng, Hongli Li, Peng Gao
来源:
Molecular Cancer
摘要:
乳腺癌是最常见的威胁女性健康的恶性肿瘤。研究长非编码RNA(lncRNA)在乳腺癌中的作用已受到关注,但具体机制尚不清楚。在本研究中,我们探讨了lncRNA BC069792在乳腺癌中的作用。我们在细胞培养和小鼠模型中进行了体外和体内功能实验。利用高通量下一代测序技术和实时荧光定量PCR技术评估差异表达基因和mRNA表达量,利用Western blot和免疫组化染色检测蛋白质表达。RNA免疫共沉淀实验和双荧光素酶活性实验用于评估竞争内源性RNA(ceRNA),并通过救援和突变实验进行验证。我们发现,在乳腺癌组织中,lncRNA BC069792的表达水平较低,并在高病理分级、淋巴结转移和高Ki-67指数组的乳腺癌中显著降低。此外,BC069792能够抑制体内外的乳腺癌细胞增殖、侵袭和转移。机械地说,BC069792作为分子海绵吸附hsa-miR-658和hsa-miR-4739,上调钾电压门控通道Q4(KCNQ4)的蛋白表达,抑制JAK2和p-AKT的活性,从而发挥抑制乳腺癌生长的作用。LncRNA BC069792在乳腺癌中扮演肿瘤抑制基因的角色,并且是乳腺癌的新的诊断指标和治疗靶点。©2023年作者。
Breast cancer is the most common malignant tumor that threatens women's health. Attention has been paid on the study of long- non-coding RNA (lncRNA) in breast cancer. However, the specific mechanism remains not clear.In this study, we explored the role of lncRNA BC069792 in breast cancer. In vitro and in vivo functional experiments were carried out in cell culture and mouse models. High-throughput next-generation sequencing technology and real-time fluorescence quantitative PCR technology were used to evaluate differentially expressed genes and mRNA expression, Western blot and immunohistochemical staining were used to detect protein expression. RNA immunoprecipitation assay and dual-luciferase activity assay were used to evaluate the competing endogenous RNAs (ceRNA), and rescue and mutation experiments were used for verification.We found that lncRNA BC069792 was expressed at a low level in breast cancer tissues, and significantly decreased in breast cancer with high pathological grade, lymph node metastasis and high Ki-67 index groups. Moreover, BC069792 inhibited the proliferation, invasion and metastasis of breast cancer cells in vitro and in vivo. Mechanically, BC069792 acts as a molecular sponge to adsorb hsa-miR-658 and hsa-miR-4739, to up-regulate the protein expression of Potassium Voltage-Gated Channel Q4 (KCNQ4), inhibits the activities of JAK2 and p-AKT, and plays a role in inhibiting breast cancer growth.LncRNA BC069792 plays the role of tumor suppressor gene in breast cancer and is a new diagnostic index and therapeutic target in breast cancer.© 2023. The Author(s).