Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of University of South China, No. 35 Jiefang Avenue, Fengxiang District, Hengyang, 421001, Hunan province, China.
Hengyang Medical College, University of South China, Hengyang, 421001, Hunan province, China.
Breast Cancer Res Treat. 2021 Jul;188(1):1-14. doi: 10.1007/s10549-021-06190-y. Epub 2021 Mar 29.
Breast cancer (BC) is the most prevalent cancer in women with an estimated incidence of 10% and the leading cause of mortality due to its heterogenous property and high metastasis rate. Development of novel therapy is very necessary and requires an understanding of molecular mechanisms. We investigated the function of SNHG6/miR-543/LAMC1 axis in BC.
Human BC tissues were obtained from diagnosed patients. BC cell lines and normal breast cells were used. QRT-PCR and Western blotting were employed to measure expression levels of SNHG6, miR-543, LAMC1, EMT-related proteins, and PI3K/AKT pathway. Dual-luciferase assay was performed to validate interactions of SNHG6/miR-543 and miR-543/LAMC1. Colony formation assay, flow cytometry, scratch wound healing assay, and transwell assay were utilized to assess the proliferation, apoptosis, migration, and invasion of BC cells. Nude mouse xenograft model was used the evaluate the function of SNHG6/miR-543 in tumor growth in vivo.
SNHG6 and LAMC1 were elevated, but miR-543 was reduced in BC tissues and cells. SNHG6 interacted directly with miR-543, while miR-543 targeted LAMC1. Knockdown of SNHG6 suppressed BC cell proliferation, migration, invasion, EMT, and PI3K/AKT pathway, but promoted cell apoptosis, while miR-543 inhibitor or overexpression of LAMC1 reversed those effects. Overexpression of LAMC1 also blocked the effects of miR-543 on BC cell proliferation, migration, invasion, and EMT. Knockdown of SNHG6 restrained BC growth in vivo, while miR-543 inhibitor inhibited that suppression.
SNHG6 promoted EMT and BC cell proliferation and migration by acting as a miR-543 sponge and disinhibiting LAMC1/PI3K/AKT pathway. SNHG6/miR-543/LAMC1 axis could serve as candidates for the development of therapeutic strategies for BC.
乳腺癌（BC）是女性中最常见的癌症，发病率估计为 10%，由于其异质性和高转移率，是导致死亡的主要原因。开发新的治疗方法非常必要，需要了解分子机制。我们研究了 SNHG6/miR-543/LAMC1 轴在 BC 中的作用。
从诊断为 BC 的患者中获得人 BC 组织。使用 BC 细胞系和正常乳腺细胞。采用 QRT-PCR 和 Western blot 检测 SNHG6、miR-543、LAMC1、EMT 相关蛋白和 PI3K/AKT 通路的表达水平。双荧光素酶报告实验验证 SNHG6/miR-543 和 miR-543/LAMC1 的相互作用。集落形成实验、流式细胞术、划痕愈合实验和 Transwell 实验用于评估 BC 细胞的增殖、凋亡、迁移和侵袭。裸鼠异种移植模型用于评估 SNHG6/miR-543 在体内肿瘤生长中的作用。
SNHG6 和 LAMC1 在 BC 组织和细胞中升高，而 miR-543 降低。SNHG6 与 miR-543 直接相互作用，而 miR-543 靶向 LAMC1。SNHG6 敲低抑制 BC 细胞增殖、迁移、侵袭、EMT 和 PI3K/AKT 通路，但促进细胞凋亡，而 miR-543 抑制剂或 LAMC1 过表达则逆转这些作用。LAMC1 的过表达也阻断了 miR-543 对 BC 细胞增殖、迁移、侵袭和 EMT 的作用。SNHG6 敲低抑制体内 BC 生长，而 miR-543 抑制剂抑制了这种抑制作用。
SNHG6 通过充当 miR-543 海绵和解除 LAMC1/PI3K/AKT 通路的抑制作用，促进 EMT 和 BC 细胞增殖和迁移。SNHG6/miR-543/LAMC1 轴可作为开发 BC 治疗策略的候选物。
