Breast cancer (BC) is considered the leading cause of
cancer- related death in women worldwide [1–4]. At pre-
sent, 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.
Noncoding RNAs (ncRNAs) have become the focus of
“next generation” biology , which consist of long non-
coding RNAs (lncRNAs) and microRNAs (miRNAs). Until
now, a few lncRNAs have been demonstrated to be dys-
regulated in breast cancer, which is closely related to breast
cancer diagnosis and prognosis [8, 9]. HOX transcript
antisense intergenic RNA (HOTAIR) located in chromo-
some 12 and owned 2.2 kb in length approximately, which
is transcribed from the HOXC locus and epigenetically
acts as a repressor of HOXD . In addition, lncRNA
HOTAIR has been found to be closely associated with
cell metastasis in multiple cancers, such as colorectal ,
hepatocellular , pancreatic , gastrointestinal stromal
, lung , and breast  carcinomas. Notably,
LncRNA HOTAIR inﬂuences cell growth, migration, invasion,
and apoptosis via the miR- 20a- 5p/HMGA2 axis in breast
, Donghua Geng
, Shuqiang Li
, Zhaofu Chen
& Ming Sun
Department of General Surgery, Shengjing Hospital Afﬁliated China Medical University, Shenyang 110004, Liaoning, China
Department of Urology, Shengjing Hospital Afﬁliated China Medical University, Shenyang 110004, Liaoning, China
© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use,
distribution and reproduction in any medium, provided the original work is properly cited.
Breast cancer, HMGA2, lncRNA HOTAIR,
Ming Sun, Department of Urology, Shengjing
Hospital Afﬁliated China Medical University,
No. 36 Sanhao Street, Heping District,
Shenyang 110004, Liaoning, China.
Tel: +86 024 96615;
No funding information provided.
Received: 3 November 2017; Revised: 18
December 2017; Accepted: 30 December
Cancer Medicine 2018; 7(3):842–855
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 as-
sessed by qRT- PCR. Cell viability was conﬁrmed using MTT and colony forma-
tion 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 correla-
tion 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 HO-
TAIR. 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 HO-
TAIR affected cell growth, metastasis, and apoptosis via the miR- 20a- 5p/HMGA2
axis in breast cancer.