Abstract

Emerging evidences have indicated that long non-coding RNAs (lncRNAs) are pivotal regulators of tumor development and progression. HNF1A-AS1 (HNF1A antisense RNA 1, C12 or f27) is a novel long non-coding RNA that acts as a potential biomarker and is involved in development and progression of several cancers. Nevertheless, we know nothing about the clinical significance and molecular mechanism of HNF1A-AS1 in bladder cancer. In this study, we found that HNF1A-AS1 is significantly up-regulated in bladder cancer. Further experiments had demonstrated that silencing HNF1A-AS1 in bladder cancer cells could inhibit the proliferation and induce apoptosis. Mechanistically, we found down-regulated of HNF1A-AS1 increased the expression of miR-30b-5p and subsequently inhibited the expression of Bcl-2, in a ceRNA-dependent way. Moreover, knockdown of miR-30b-5p reversed cell proliferation inhibition and cell apoptosis induced by silencing HNF1A-AS1. In conclusions, we demonstrated that HNF1A-AS1 plays an important regulatory role in bladder cancer and shed new light on lncRNA-directed diagnostic and therapeutics in bladder cancer.

Highlights

  • Bladder cancer is the ninth most common malignancy all over the world and it is estimated that there are 386,000 new cases are diagnosed worldwide annually [1,2,3,4]

  • HNF1A-AS1 was up-regulated in bladder cancer cell lines compared to corresponding normal urothelial cell line SV-HUC-1 (Figure 1E)

  • There are no specific symptoms for patents with bladder cancer at the early stage, some bladder cancers are found at advanced stage when treatments are less effective [35]

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Summary

Introduction

Bladder cancer is the ninth most common malignancy all over the world and it is estimated that there are 386,000 new cases are diagnosed worldwide annually [1,2,3,4]. The long non-coding RNAs (lncRNAs) are important new members of the ncRNA family with greater than 200 nucleotides in length [15, 16]. The rapid development of RNA genomics has highlighted the role of long non-coding RNAs (lncRNAs) in many human diseases, especially in cancers [17, 18]. Recent evidences have showed that many lncRNAs play important regulatory roles in diverse biological processes of cancers, such as UCA-1, HOTAIR, H19, MALAT1, ZEB1-AS1, PVT-1, PANDAR and etc [19,20,21,22,23,24,25]. HNF1A-AS1 (HNF1A antisense RNA 1) is a novel identified lncRNA with 2455 nucleotides in length and localized at the chromosome 12 [26]. The biological function and underlying mechanism of action of HNF1AAS1 in bladder cancer is completely unknown

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