Long non-coding RNA heart and neural crest derivatives expressed 2-antisense RNA 1 overexpression inhibits the proliferation of cancer cells by reducing RUNX2 expression in triple-negative breast cancer

长链非编码RNA心脏和神经嵴衍生物表达2-反义RNA 1过表达通过降低三阴性乳腺癌中RUNX2表达来抑制癌细胞增殖

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作者:Min Wei, Lei Liu, Zhiwei Wang

Abstract

The role of long non-coding RNA heart and neural crest derivatives expressed 2-antisense RNA 1 (lncRNA HAND2-AS1) in tumor suppression has been reported in a number of cancer types, while its functionality in triple-negative breast cancer (TNBC) remains unclear. The present study aimed to investigate the involvement of lncRNA HAND2-AS1 in TNBC using different methodologies. HAND2-AS1 and RUNX2 expression was analyzed using reverse transcription-quantitative PCR and western blot analysis. Diagnostic analysis was performed using receiver operating characteristic curve. Overexpression experiments were performed to analyze the interaction between HAND2-AS1 and RUNX2 while the Cell Counting Kit-8 assay was performed to analyze cell proliferation. In patients with early-stage TNBC, the expression level of lncRNA HAND2-AS1 was downregulated, whilst runt-related transcription factor 2 (RUNX2) mRNA was upregulated in tumor tissues, compared with paired healthy tissues. Expression levels of lncRNA HAND2-AS1 and RUNX2 mRNA were inversely correlated in tumor tissues, but not in paired healthy tissues. Decreased plasma expression levels of lncRNA HAND2-AS1 were observed in TNBC patients compared with those in healthy controls, and the downregulation of lncRNA HAND2-AS1 distinguished patients with TNBC from healthy controls. lncRNA HAND2-AS1 overexpression inhibited RUNX2 expression, whilst RUNX2 overexpression did not significantly affect lncRNA HAND2-AS1 expression in the MDA-MB-231 and BT-20 cell lines. lncRNA HAND2-AS1 overexpression resulted in the inhibition of cell proliferation, while RUNX2 overexpression promoted the proliferation of TNBC cells. RUNX2 overexpression partially reversed the effects of lncRNA HAND2-AS1 overexpression on cancer cells. Therefore lncRNA HAND2-AS1 may inhibit the proliferation of cancer cells by inhibiting RUNX2 expression in TNBC.

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