Long non-coding RNA HNF1A-AS1 promotes cell proliferation and invasion via regulating miR-17-5p in non-small cell lung cancer

Abstract

Long non-coding RNA HNF1A-antisense 1 (lncRNA HNF1A-AS1) plays important roles in the progression of human tumors. The aim of this study is to unravel the underlying mechanism of HNF1A-AS1 in non-small cell lung cancer (NSCLC). In the present study, we found that HNF1A-AS1 was upregulation in NSCLC tissues and cell lines. High HNF1A-AS1 expression was associated with patients’ advanced TNM stage and lymph node metastasis. Reduced HNF1A-AS1 expression inhibited lung cancer cells proliferation, invasion and increased cells apoptosis rate. Bioinformatics analysis and luciferase reporter assay revealed that HNF1A-AS1 interacted with miR-17-5p by directly targeting it. Rescue experiments showed that miR-17-5p suppression reversed the tumor-suppressing role of HNF1A-AS1 knockdown on NSCLC progression. Conclusion, our data indicated that lncRNA HNF1A-AS1 promoted lung cancer cells proliferation and invasion via regulating miR-17-5p, suggesting that HNF1A-AS1 could act as a potent therapeutic strategy for the treatment of NSCLC patients.

Introduction

Lung cancer is the top leading cause of cancer-related death worldwide [1]. Non-small cell lung cancer (NSCLC) accounts for approximately 75–80% of all lung cancer [2]. Unfortunately, despite the recent advances in surgery, chemotherapy and molecular-targeted therapy, the outcome of NSCLC patients remain unsatisfied. The 5-year survival of lung cancer patients is still very poor mostly due to metastasis [3,4]. Therefore, the identification of potential therapeutic strategies is an urgent need to define new molecular-targeted therapy for NSCLC.

Long non-coding RNAs (lncRNAs) are a class of transcripts longer than 200 nt and lack of protein-coding capacity [5]. Increasing number of studies demonstrated that lncRNAs play crucial regulatory roles in various biological processes, such as transcriptional regulation, cellular proliferation and differentiation [6,7]. Dysregulated expression of lncRNAs have been established in various cancers and are generally related to oncogenic or cancer-suppressive processes. For example, Zhang et al showed that lncRNA HCG11 was downregulated and correlated with advanced clinical pathologic features in prostate cancer [8]. Xiong et al. showed that lncRNA HEIRCC promoted renal cell carcinoma metastasis by inducing epithelial-mesenchymal transition [9]. Zhao et al. found that lncRNA ANRIL promoted the invasion and metastasis of thyroid cancer cells through TGF-β/Smad signaling pathway [10]. However, the role of lncRNAs in tumor progression remains unclear.

Recently, A growing body of evidence has suggested that many lncRNAs could function as competing endogenous RNAs (ceRNA) to prevent a single miRNA or multiple miRNAs from binding to their regulatory targets [11]. For example, Jin et al found that lncRNA SPRY4-IT1 promoted proliferation and invasion by acting as a ceRNA of miR-101-3p in colorectal cancer cells [12]. Zhao et al found that lncRNA PVT1 promoted pancreatic cancer cells proliferation and migration through acting as a molecular sponge to regulate miR-448 [13]. Wang et al showed that STAT3-mediated upregulation of lncRNA HOXD-AS1 as a ceRNA facilitates liver cancer metastasis by regulating SOX4 [14]. However, the functional role and underlying molecular mechanism of HNF1A-AS1 in lung cancer remain unclear.

In the present study, we aim to investigate the impact of lncRNA HNF1A-AS1 on NSCLC progression. Our data showed that expression of HNF1A-AS1 was upregulated in NSCLC. HNF1A-AS1 is involved in the proliferation and invasion progress of NSCLC cells by regulating miR-17-5p expression.