Abstract
To study the regulatory effect of lncRNA HOTAIR/miR‐20a‐5p/HMGA2 axis on breast cancer (BC) cell growth, cell mobility, invasiveness, and apoptosis. The microarray data of lncRNAs and mRNAs with differential expression in BC tissues were analyzed in the Cancer Genome Atlas (TCGA) database. LncRNA HOX transcript antisense RNA (lncRNA HOTAIR) expression in BC was assessed by qRT‐PCR. Cell viability was confirmed using MTT and colony formation assay. Cell apoptosis was analyzed by TdT‐mediated dUTP nick‐end labeling (TUNEL) assay. Cell mobility and invasiveness were testified by transwell assay. RNA pull‐down and dual luciferase assay were used for analysis of the correlation between lncRNA HOTAIR and miR‐20a‐5p, as well as relationship of miR‐20a‐5p with high mobility group AT‐hook 2 (HMGA2). Tumor xenograft study was applied to confirm the correlation of lncRNA HOTAIR/miR‐20a‐5p/HMGA2 axis on BC development in vivo. The expression levels of the lncRNA HOTAIR were upregulated in BC tissues and cells. Knockdown lncRNA HOTAIR inhibited cell propagation and metastasis and facilitated cell apoptosis. MiR‐20a‐5p was a target of lncRNA HOTAIR and had a negative correlation with lncRNA HOTAIR. MiR‐20a‐5p overexpression in BC suppressed cell growth, mobility, and invasiveness and facilitated apoptosis. HMGA2 was a target of miR‐20a‐5p, which significantly induced carcinogenesis of BC. BC cells progression was mediated by lncRNA HOTAIR via affecting miR‐20a‐5p/HMGA2 in vivo. LncRNA HOTAIR affected cell growth, metastasis, and apoptosis via the miR‐20a‐5p/HMGA2 axis in breast cancer.
Highlights
Breast cancer (BC) is considered the leading cause of cancer-related death in women worldwide [1,2,3,4]
LncRNA HOX transcript antisense intergenic RNA (HOTAIR) had been reported to act as tumor-promoting molecular in multiple tumors, and it was significantly upregulated in BC tissues, predicting its expression and biological function in BC tumorigenesis (Fig. 1A and B)
The prognosis analysis of long noncoding RNAs (lncRNAs) HOTAIR and the results showed that the high expression of lncRNA HOTAIR brought out an adverse role in survival depending on Kaplan-M eier analysis (Fig. 1C)
Summary
Breast cancer (BC) is considered the leading cause of cancer-related death in women worldwide [1,2,3,4]. Gene therapy against neoplasms has been a novel research focus in cancer treatment [5, 6]. Using gene therapy against BC, it is an urgent need to elucidate novel mechanisms correlated with BC development. LncRNA HOTAIR has been found to be closely associated with cell metastasis in multiple cancers, such as colorectal [11], hepatocellular [12], pancreatic [13], gastrointestinal stromal [14], lung [15], and breast [16] carcinomas.
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