Long Non-coding RNA HOTAIR Drives Breast Cancer Progression Through miR-3619-5p/MGAT5 Axis

HOX Transcript Antisense Intergenic RNA (HOTAIR) is a long-noncoding RNA that plays important roles in tumorigenesis. However, the underlying molecular mechanism of HOTAIR in breast cancer is not fully understood.

In this study, high-throughput sequencing was carried out to analyze breast cancer transcriptomic changes after HOTAIR was overexpressed in MCF-7 cells. Gain- and loss-of-function assays were used to examine the effects of HOTAIR on the progression of breast cancer. A double-luciferase reporter assay was used to verify the possible correlation among HOTAIR, miR-3619-5p, and MGAT5.

We found that HOTAIR was overexpressed in breast cancer tissues and was related to the prognosis of breast cancer patients. Overexpression of HOTAIR promoted the proliferation, migration, and invasion of breast cancer cells. MiR-3619-5p was downregulated, and MGAT5 was upregulated in HOTAIR-overexpressing breast cancer cells compared with the negative cells. MiR-3619-5p was verified to be the target of HOTAIR, and MGAT5 was identified as a target of miR-3619-5p. MiR-3619- 5p rescued the effect of HOTAIR on the proliferation of breast cancer cells. MGAT5 silencing inhibited the proliferation of breast cancer cells. In addition, high-throughput sequencing indicated that HOTAIR overexpression altered the whole transcriptome of breast cancer.

Our findings suggested that HOTAIR may drive breast cancer progression through the miR-3619-5p/MGAT5 axis.

HOTAIR might be a potential therapeutic target for breast cancer.