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Long Noncoding RNA Regulator of Reprogramming Regulates Cell Growth, Metastasis, and Cisplatin Resistance in Gastric Cancer via miR-519d-3p/HMGA2 Axis.
Cancer Biother Radiopharm. 2020 Jul 02 [Online ahead of print]CB

Abstract

Background:

Gastric cancer (GC) is a common tumor found worldwide, and cisplatin is the first-line agent for the treatment of GC. However, the resistance to cisplatin is an obstacle. Here, we aim to explore the biological mechanism of long noncoding RNA regulator of reprogramming (ROR) in the cisplatin resistance of GC. Materials and

Methods:

ROR, miR-519d-3p, and high mobility group protein A2 (HMGA2) expression in GC tissues and cells were measured by quantitative real-time polymerase chain reaction and Western blot. Cell viability, migration, invasion, and apoptosis were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, transwell assay, and flow cytometry, respectively. The relative protein expression was detected by Western blot. The interactions between miR-519d-3p and ROR, HMGA2 were predicted using miRcode and starBase v2.0 online database, and then verified by dual luciferase reporter assay and RNA immunoprecipitation assay. In addition, the xenograft tumor mouse model was constructed to verify the biological role of ROR in vivo.

Results:

The levels of ROR, HMGA2 were significantly upregulated, and miR-519d-3p was apparently downregulated in GC tissues and cells. The miRcode and starBase v2.0 online websites and dual luciferase reporter assay validated that miR-519d-3p directly interacted with ROR and HMGA2. Furthermore, ROR knockdown downregulated HMGA2 to restrain cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and cisplatin resistance in GC cells by targeting miR-519d-3p. In addition, the depletion of ROR repressed the xenograft tumor growth in vivo.

Conclusion:

In conclusion, we first found the ROR/miR-519d-3p/HMGA2 regulatory network to regulate cell proliferation, migration, invasion, EMT, and cisplatin resistance in GC, and this may shed light on the GC tumorigenesis.

Authors+Show Affiliations

Department of Gastroenterology, The People's Hospital of Zhangqiu, Jinan, China.Department of Gastroenterology, The People's Hospital of Zhangqiu, Jinan, China.Department of Computer Tomography (CT), The People's Hospital of Zhangqiu, Jinan, China.Department of Gastroenterology, The Second Hospital of Shandong University, Jinan, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32614615

Citation

Jin, Wenhua, et al. "Long Noncoding RNA Regulator of Reprogramming Regulates Cell Growth, Metastasis, and Cisplatin Resistance in Gastric Cancer Via miR-519d-3p/HMGA2 Axis." Cancer Biotherapy & Radiopharmaceuticals, 2020.
Jin W, Zhang H, Li M, et al. Long Noncoding RNA Regulator of Reprogramming Regulates Cell Growth, Metastasis, and Cisplatin Resistance in Gastric Cancer via miR-519d-3p/HMGA2 Axis. Cancer Biother Radiopharm. 2020.
Jin, W., Zhang, H., Li, M., & Lin, S. (2020). Long Noncoding RNA Regulator of Reprogramming Regulates Cell Growth, Metastasis, and Cisplatin Resistance in Gastric Cancer via miR-519d-3p/HMGA2 Axis. Cancer Biotherapy & Radiopharmaceuticals. https://doi.org/10.1089/cbr.2019.3525
Jin W, et al. Long Noncoding RNA Regulator of Reprogramming Regulates Cell Growth, Metastasis, and Cisplatin Resistance in Gastric Cancer Via miR-519d-3p/HMGA2 Axis. Cancer Biother Radiopharm. 2020 Jul 2; PubMed PMID: 32614615.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long Noncoding RNA Regulator of Reprogramming Regulates Cell Growth, Metastasis, and Cisplatin Resistance in Gastric Cancer via miR-519d-3p/HMGA2 Axis. AU - Jin,Wenhua, AU - Zhang,Hua, AU - Li,Meng, AU - Lin,Sen, Y1 - 2020/07/02/ PY - 2020/7/3/entrez PY - 2020/7/3/pubmed PY - 2020/7/3/medline KW - HMGA2 KW - cisplatin KW - gastric cancer KW - lncRNA ROR KW - miR-519d-3p JF - Cancer biotherapy & radiopharmaceuticals JO - Cancer Biother. Radiopharm. N2 - Background: Gastric cancer (GC) is a common tumor found worldwide, and cisplatin is the first-line agent for the treatment of GC. However, the resistance to cisplatin is an obstacle. Here, we aim to explore the biological mechanism of long noncoding RNA regulator of reprogramming (ROR) in the cisplatin resistance of GC. Materials and Methods: ROR, miR-519d-3p, and high mobility group protein A2 (HMGA2) expression in GC tissues and cells were measured by quantitative real-time polymerase chain reaction and Western blot. Cell viability, migration, invasion, and apoptosis were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, transwell assay, and flow cytometry, respectively. The relative protein expression was detected by Western blot. The interactions between miR-519d-3p and ROR, HMGA2 were predicted using miRcode and starBase v2.0 online database, and then verified by dual luciferase reporter assay and RNA immunoprecipitation assay. In addition, the xenograft tumor mouse model was constructed to verify the biological role of ROR in vivo. Results: The levels of ROR, HMGA2 were significantly upregulated, and miR-519d-3p was apparently downregulated in GC tissues and cells. The miRcode and starBase v2.0 online websites and dual luciferase reporter assay validated that miR-519d-3p directly interacted with ROR and HMGA2. Furthermore, ROR knockdown downregulated HMGA2 to restrain cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and cisplatin resistance in GC cells by targeting miR-519d-3p. In addition, the depletion of ROR repressed the xenograft tumor growth in vivo. Conclusion: In conclusion, we first found the ROR/miR-519d-3p/HMGA2 regulatory network to regulate cell proliferation, migration, invasion, EMT, and cisplatin resistance in GC, and this may shed light on the GC tumorigenesis. SN - 1557-8852 UR - https://www.unboundmedicine.com/medline/citation/32614615/Long_Noncoding_RNA_Regulator_of_Reprogramming_Regulates_Cell_Growth,_Metastasis,_and_Cisplatin_Resistance_in_Gastric_Cancer_via_miR-519d-3p/HMGA2_Axis L2 - https://www.liebertpub.com/doi/10.1089/cbr.2019.3525?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -
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