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Platycodin D (PD) regulates LncRNA-XIST/miR-335 axis to slow down bladder cancer progression in vitro and in vivo.
- Source :
-
Experimental cell research [Exp Cell Res] 2020 Nov 01; Vol. 396 (1), pp. 112281. Date of Electronic Publication: 2020 Sep 10. - Publication Year :
- 2020
-
Abstract
- Recently, increasing evidences indicated that Platycodin D (PD) served as an effective anti-tumor drug for cancer treatment in clinic. However, the molecular mechanisms are still unclear. In the present study, we proved that PD regulated LncRNA-XIST/miR-335 axis to hamper the development of bladder cancer in vitro and in vivo. Mechanistically, PD inhibited malignant phenotypes, including cell proliferation, invasion, migration and epithelial-mesenchymal transition (EMT), and promoted cell apoptosis in bladder cancer cells in a time- and dose-dependent manner. In addition, the following experiments validated that PD inhibited LncRNA-XIST expressions, while increased miR-335 expression levels in bladder cancer cells. Next, by conducting the dual-luciferase reporter gene system assay and RNA pull-down assay, we validated that LncRNA-XIST inhibited miR-335 expressions through acting as RNA sponges, and the promoting effects of PD stimulation on miR-335 levels were abrogated by upregulating LncRNA-XIST. Interestingly, both silencing LncRNA-XIST and miR-335 overexpression enhanced the inhibiting effects of PD on the malignant phenotypes in bladder cancer cells. Consistently, the xenograft tumor-bearing mice models were established, and the data indicated that PD slowed down tumor growth and inhibited tumorigenesis in vivo, which were also aggravated by downregulating LncRNA-XIST. In general, analysis of data proved that targeting LncRNA-XIST/miR-335 axis was novel to enhance the anti-tumor effects of PD in bladder cancer in vitro and in vivo, and this study provided alternative therapeutic strategies for bladder cancer treatment in clinic.<br /> (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Apoptosis drug effects
Apoptosis genetics
Carcinogenesis genetics
Carcinogenesis metabolism
Carcinogenesis pathology
Cell Line, Tumor
Cell Movement drug effects
Cell Proliferation drug effects
Disease Progression
Epithelial Cells metabolism
Epithelial Cells pathology
Epithelial-Mesenchymal Transition drug effects
Epithelial-Mesenchymal Transition genetics
Gene Expression Regulation, Neoplastic
Humans
Ki-67 Antigen genetics
Ki-67 Antigen metabolism
Mice
Mice, Nude
MicroRNAs metabolism
RNA, Long Noncoding antagonists & inhibitors
RNA, Long Noncoding metabolism
RNA, Small Interfering genetics
RNA, Small Interfering metabolism
Signal Transduction
Tumor Burden drug effects
Urinary Bladder Neoplasms genetics
Urinary Bladder Neoplasms metabolism
Urinary Bladder Neoplasms pathology
Xenograft Model Antitumor Assays
Antineoplastic Agents, Phytogenic pharmacology
Carcinogenesis drug effects
MicroRNAs genetics
RNA, Long Noncoding genetics
Saponins pharmacology
Triterpenes pharmacology
Urinary Bladder Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2422
- Volume :
- 396
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Experimental cell research
- Publication Type :
- Academic Journal
- Accession number :
- 32919956
- Full Text :
- https://doi.org/10.1016/j.yexcr.2020.112281