HOTAIRM1 competed endogenously with miR-148a to regulate DLGAP1 in head and neck tumor cells

HOTAIRM1 与 miR-148a 内源性竞争调节头颈部肿瘤细胞中的 DLGAP1

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作者:Mei Zheng, Xingguang Liu, Qin Zhou, Gangli Liu

Abstract

This study is aimed to explore the regulatory effect of lncRNA HOTAIR/miR-148a/DLGAP1 axis on head and neck tumor (HNT) cell growth, cell mobility, and invasiveness. HOTAIRM1, miR-148a, and DLGAP1 level in HNT tissues and adjacent normal tissues were measured by qRT-PCR. Cell Counting Kit-8 (CCK-8) and Transwell (migration and invasion) assay were used to survey the influence of HOTAIRM1, miR-148a, and DLGAP1 on Fadu cells. Nude mouse xenograft was utilized to validate the influence of HOTAIRM1 in vivo. Dual-luciferase reporter assay confirms the relationship between HOTAIRM1 and miR-148a, miR-148a, and DLGAP1. The expression level of HOTAIRM1 was downregulated in human HNT tissues and cells. Overexpression of HOTAIRM1 significantly moderated Fadu cells proliferation, apoptosis, migration, and invasion in vitro and impaired the tumorigenesis in vivo. The expression level of miR-148a was upregulated in human HNT tissue compared to the adjacent tissues. We identified that miR-148a was a target of HOTAIRM1 and its expression levels were reduced by HOTAIRM1. Transfection of miR-148a mimics increased proliferation, migration, and invasion of Fadu cells. DLGAP1 was identified as a novel target of miR-148a and its expression level was promoted by either HOTAIRM1 overexpression or miR-148a knockdown. Overexpression of DLGAP1 also facilitated the cell viability and metastasis of Fadu cells. HOTAIRM1 was confirmed as a tumor suppressor via sponging miR-148a and promote the expression of DLGAP1, which could be regarded as an important target for the prevention and treatment of HNT.

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