Knockdown of long noncoding RNA FGFR3- AS1 induces cell proliferation inhibition, apoptosis and motility reduction in bladder cancer

Abstract Background Growing evidence has shown that the association of long noncoding RNA/microRNA/mRNA is implicated in tumor initiation, development, and progression. Long noncoding RNA (lncRNA) HAND2-AS1 exhibits anti-cancer effects in diverse cancers. However, the knowledge of HAND-AS1 in bladder cancer development remains unknown. Methods LncRNA and miRNA microarray were conducted to explore different expressed RNA in primary bladder cancer specimens. RNA-RNA interaction prediction tools miRcode (http://www.mircode.org/), DIANA-lncBase v2 (https://carolina.imis.athena-innovation.gr/diana_tools/web/index.php?r=lncbasev2%2Findex-experimental), DIANA-TarBase v.8 (https://carolina.imis.athena-innovation.gr/diana_tools/web/index.php?r=tarbasev8%2Findex) and miRDB (http://www.mirdb.org/) were employed to predict the interactions between RNA. Bladder cancer cell lines were used to perform cell proliferation and apoptosis assays. Western blot and quantitative Real-time Polymerase Chain Reaction were used to determine the expression of protein and RNA, separately. Dual luciferase assay was conducted to determine the activity of 3’untranslational region of RARB. Furthermore, 5637 human bladder cancer mouse models were established to investigate the interactions of lncRNA: miRNA: mRNA in vivo.Results Based on the analysis of RT2 lncRNA PCR Arrays, we validated HAND2-AS1 declined in bladder cancer and correlated with the depth of invasion and grades negatively. Overexpression of HAND2-AS1 in human bladder cancer cells 5637 and RT4 hampered cell proliferation by provoking Caspase 3-triggered cell apoptosis. Besides, one of the HAND2-AS1 sponge, miR-146, upregulated in bladder cancer and targeted the tumor suppressor, retinoic acid receptor beta (RARB). We further demonstrated the HAND2-AS1: miR-146: RARB complex promoted Caspase 3-mediated apoptosis by suppressing COX-2 expression. Finally, results observed in mouse xenografts suggested that HAND2-AS1 diminished miR-146 expression, thereby reversing the suppression of miR-146 on RARB-mediated apoptosis and contributing to bladder cancer regression. Conclusion The present study shed light on the fact that lncRNA HAND2-AS1 exerted as a tumor suppressor by releasing RARB from miR-146, leading to inhibition of tumor proliferation and invasion. The findings expanded the knowledge of HAND2-AS-mediated regulatory networks, provided novel insights to improve the RARB-targeted regimens against bladder cancer.

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The YAP1 oncogene contributes to bladder cancer cell proliferation and migration by regulating the H19 long noncoding RNA

Urologic Oncology Seminars and Original Investigations ◽

10.1016/j.urolonc.2015.06.003 ◽

2015 ◽

Vol 33 (10) ◽

pp. 427.e1-427.e10 ◽

Cited By ~ 22

Author(s):

Shi Li ◽

Zhe Yu ◽

San-San Chen ◽

Fei Li ◽

Cheng-Yong Lei ◽

...

Keyword(s):

Cell Proliferation ◽

Bladder Cancer ◽

Cancer Cell ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Bladder Cancer Cell ◽

Cancer Cell Proliferation ◽

Cell Proliferation And Migration ◽

And Migration ◽

Proliferation And Migration

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Downregulation of Long Noncoding RNA LUCAT1 Suppresses the Migration and Invasion of Bladder Cancer by Targeting miR-181c-5p

BioMed Research International ◽

10.1155/2020/4817608 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Yifan Chen ◽

Wentao Zhang ◽

Liliang Shen ◽

Aimaitiaji Kadier ◽

Jianhua Huang ◽

...

Keyword(s):

Cell Proliferation ◽

Bladder Cancer ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Molecular Mechanisms ◽

Migration And Invasion ◽

Cancer Tissue ◽

Dependent Manner ◽

Normal Bladder ◽

Bladder Cells

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.

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