Breast Cancer

SNHG6[LncRNA]

miR-543[miRNA]

LAMC1[mRNA]

BC cell lines

Homo sapiens (human)

Breast Cancer Res Treat. 2021 Mar 29. doi: 10.1007/s10549-021-06190-y.

LncRNA SNHG6 promotes breast cancer progression and epithelial-mesenchymal transition via miR-543/LAMC1 axis.

qRT-PCR;Western blot;Flow Cytometry assay;luciferase assay;

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.