Abstract
Purpose The long noncoding RNA LUCAT1 (lung cancer-associated transcript 1) has been reported to be highly expressed in bladder cancer samples, but its role and molecular mechanisms need to be elucidated. Methods Bioinformatics methods show that miR-181c-5p is a target of LUCAT1. Here, we aimed to reveal whether LUCAT1 participates in the development of bladder cancer via targeting miR-181c-5p. The expression levels of LUCAT1 and miR-181c-5p were detected by RT-PCR technology in bladder cells and tissues. The effects of the LUCAT1/miR-181c-5p axis on cell proliferation, migration, invasion, and apoptosis were tested by CCK-8, wound healing, Transwell chambers, and flow cytometry assays. The expressions of apoptosis/migration-related proteins were detected by western blotting assays. Results The results demonstrated that LUCAT1 was overexpressed in bladder cancer tissue and cells, while miR-181c-5p showed a low expression pattern as compared to normal bladder cells and tissues. Cell proliferation, migration, and invasion capacities were significantly impaired, and cell apoptosis was enhanced when LUCAT1 was silenced in UM-UC-3 and T24 cell lines, but this effect was abolished by miR-181c-5p downregulation. In addition, miR-181c-5p downregulation impaired LUCAT1 downregulation which mediated the decreased expressions of Bcl2 and N-cadherin and the increased expressions of Bax and E-cadherin. Moreover, we found that KRAS was a direct target of miR-181c-5p and was under the positive regulation of LUCAT1. Conclusion Collectively, this study reveals that knockdown of LUCAT1 inhibits the migration and invasion of bladder cancer cells in a miR-181c-5p-dependent manner, which may be related to KRAS downregulation.
Highlights
Bladder cancer is a common malignant tumor which occurs in the urinary system [1] and ranks the fourth most common malignant cancer among males [2]
Using starBase, we identified that miR-181c-5p was a predicted target of LUCAT1, and the miR-181c-5p low expression level predicted a poor prognosis in bladder cancer, indicating that miR-181c-5p might play a role in LUCAT1-mediated bladder cancer progression
Great efforts were made in the investigation of bladder cancer progression, it still remains as a serious burden in worldwide due to its high recurrence rate and metastasis [16]
Summary
Bladder cancer is a common malignant tumor which occurs in the urinary system [1] and ranks the fourth most common malignant cancer among males [2]. Metastasis is a complex multistep process which contains cancer cell dissemination, transport, and colonization expansion [4, 5]. The molecular mechanisms underlying bladder cancer cell metastasis and invasion still remain incompletely clear. Long noncoding RNAs (lncRNAs) are transcripts which contain >200 nucleotides in length with no protein-coding capacity [6]. LncRNAs can modulate gene expression at chromatin organizational, transcriptional, or posttranscriptional levels [7]. Lots of studies have found that many lncRNAs are aberrantly expressed in cancers including bladder cancer, where they functions as tumor suppressors or oncogenes [6, 8, 9]. The lncRNA zinc finger E-box-binding homeobox 1-antisense 1 (ZEB1-AS1) was reported to be overexpressed in bladder cancer, and ZEB1-AS1 repression significantly inhibited cell migration and invasion [10]. Hu et al [11] demonstrated that lncRNA prostrate androgen-
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