Department of Plastic and Esthetic Surgery, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China.
Key Laboratory of Reproductive and Stem Cell Engineering, National Health and Family Planning Commission, Institute of Reproductive and Stem Cell Engineering, Basic Medicine College, Central South University, Changsha, Hunan 410078, China.
Oxid Med Cell Longev. 2021 Dec 15;2021:4586319. doi: 10.1155/2021/4586319. eCollection 2021.
Breast cancer (BRCA) is a malignant tumor with a high incidence and poor prognosis in females. However, its pathogenesis remains unclear. In this study, based on bioinformatic analysis, we found that LINC00467 was highly expressed in BRCA and was associated with tumor metastasis and poor prognosis. The genomic and epigenetic analysis showed that LINC00467 may also be regulated by copy number amplification (CNA), chromatin openness, and DNA methylation. In vitro experiments showed that it could promote the proliferation, migration, and invasion of BRCA cells. Competitive endogenous RNA (ceRNA) regulatory network analysis and weighted gene coexpression network analysis (WGCNA) suggested that LINC00467 may play a role in signaling pathways of peroxisomal lipid metabolism, immunity, and others through microRNAs (miRNAs) targeting transforming growth factor beta 2 (TGFB2). In addition, copy number amplification and high expression of LINC00467 were associated with the low infiltration of CD8+ and CD4+ T cells. In conclusion, we found that LINC00467, driven by copy number amplification and DNA demethylation, may be a potential biomarker for the diagnosis and prognosis of BRCA and a tumor promoter acting as a potential therapeutic target for BRCA as well.
乳腺癌（BRCA）是女性中发病率和预后不良的恶性肿瘤。然而，其发病机制尚不清楚。在这项研究中，我们基于生物信息学分析发现 LINC00467 在 BRCA 中高表达，与肿瘤转移和不良预后相关。基因组和表观遗传分析表明，LINC00467 也可能受到拷贝数扩增（CNA）、染色质开放性和 DNA 甲基化的调控。体外实验表明，它可以促进 BRCA 细胞的增殖、迁移和侵袭。竞争性内源 RNA（ceRNA）调控网络分析和加权基因共表达网络分析（WGCNA）表明，LINC00467 可能通过靶向转化生长因子 beta 2（TGFB2）的 microRNAs（miRNAs），在过氧化物酶体脂质代谢、免疫等信号通路中发挥作用。此外，LINC00467 的拷贝数扩增和高表达与 CD8+和 CD4+T 细胞浸润水平低有关。总之，我们发现 LINC00467 可能是 BRCA 诊断和预后的潜在生物标志物，同时作为一种潜在的治疗靶点，其通过拷贝数扩增和 DNA 去甲基化促进了 BRCA 的发生。
