LOXL1-AS1, a recently characterized long non-coding RNA (lncRNA), has been reported to modulate tumor progression in several types of cancer. However, the expression and role of LOXL1-AS1 in breast cancer remain unclear. In this study, we sought to identify novel lncRNA regulators engaged in breast cancer metastasis. To this end, we examined 42 cancer-related lncRNAs between MCF7 (with low metastatic potential) and MDA-MB-231 (with high metastatic potential) cells. These lncRNAs have been found to affect the invasiveness of several cancer types, but they are still undefined in breast cancer. Among the 42 candidates, LOXL1-AS1 is significantly increased in MDA-MB-231 cells relative to MCF7 cells. We also show that LOXL1-AS1 is upregulated in breast cancer tissues and cells compared to noncancerous counterparts. Increased LOXL1-AS1 expression is correlated with tumor stage and lymph node metastasis in breast cancer patients. Biologically, overexpression of LOXL1-AS1 enhances and knockdown of LOXL1-AS1 suppresses breast cancer cell migration and invasion. In vivo studies demonstrate that depletion of LOXL1-AS1 inhibits breast cancer metastasis. Mechanistically, LOXL1-AS1 sponges miR-708-5p to increase nuclear factor κB (NF-κB) activity. LOXL1-AS1 can also interact with EZH2 protein to enhance EZH2-mediated transcriptional repression of miR-708-5p. Rescue experiments indicate that co-expression of miR-708-5p attenuates LOXL1-AS1-induced invasiveness in breast cancer. In addition, there is a negative correlation between LOXL1-AS1 and miR-708-5p expression in breast cancer specimens. Overall, LOXL1-AS1 upregulation facilitates breast cancer invasion and metastasis by blocking miR-708-5p expression and activity. LOXL1-AS1 serves as a potential therapeutic target for breast cancer treatment.

据报道，LOXL1-AS1是最近鉴定的长非编码RNA（lncRNA），可调节多种类型癌症中的肿瘤进展。但是，LOXL1-AS1在乳腺癌中的表达和作用仍不清楚。在这项研究中，我们试图确定参与乳腺癌转移的新型lncRNA调节剂。为此，我们检查了MCF7（具有低转移潜力）和MDA-MB-231（具有高转移潜力）细胞之间的42种与癌症相关的lncRNA。已经发现这些lncRNAs影响几种癌症类型的侵袭性，但是在乳腺癌中它们仍不确定。在42个候选对象中，相对于MCF7细胞，MDA-MB-231细胞中LOXL1-AS1显着增加。我们还显示，与非癌性对应物相比，LOXL1-AS1在乳腺癌组织和细胞中表达上调。LOXL1-AS1表达增加与乳腺癌患者的肿瘤分期和淋巴结转移有关。从生物学上讲，LOXL1-AS1的过度表达增强，而LOXL1-AS1的敲低则抑制乳腺癌细胞的迁移和侵袭。体内研究表明，LOXL1-AS1的耗竭抑制了乳腺癌的转移。从机理上讲，LOXL1-AS1使miR-708-5p变海绵，以增加核因子κB（NF-κB）的活性。LOXL1-AS1还可以与EZH2蛋白相互作用，以增强EZH2介导的miR-708-5p转录抑制。救援实验表明，miR-708-5p的共表达可减弱LOXL1-AS1诱导的乳腺癌侵袭性。此外，乳腺癌样本中LOXL1-AS1和miR-708-5p表达之间呈负相关。总体而言，LOXL1-AS1的上调通过阻止miR-708-5p的表达和活性而促进乳腺癌的侵袭和转移。LOXL1-AS1可用作乳腺癌治疗的潜在治疗靶标。