SNP rs7430456 mediated LINC00578 drives triple negative breast cancer through regulating miR-143-5p expression
摘要
A large number of cancer-related single-nucleotide polymorphisms (SNPs) are distributed in the genomic regions of long non-coding RNAs (lncRNAs), yet the mechanisms linking them to cancer risk have not been fully clarified so far. This study explored LINC00578 rs7430456’s association with breast cancer susceptibility and LINC00578’s role/mechanism in triple-negative breast cancer (TNBC).
MethodsA total of 480 breast cancer patients and 460 controls were enrolled. LINC00578 rs7430456 genotyping and LINC00578 expression detection via RT-qPCR were performed. Functional assays (proliferation, migration, invasion) were conducted in TNBC cell lines, and the LINC00578-miR-143-5p interaction was explored by dual-luciferase reporter assay.
ResultsLINC00578 rs7430456 G allele and AG/GG genotypes reduced breast cancer risk. LINC00578 was upregulated in breast cancer (especially TNBC) with an AUC of 0.873 for diagnosis. LINC00578 knockdown inhibited TNBC cell proliferation, migration, and invasion. LINC00578 sponged miR-143-5p, and miR-143-5p mediated its oncogenic effects.
ConclusionsLINC00578 rs7430456 is associated with breast cancer susceptibility, and LINC00578 promotes TNBC progression via sponging miR-143-5p, being a potential biomarker and therapeutic target for breast cancer, particularly TNBC.