miR‑214 reduces cisplatin resistance by targeting netrin‑1 in bladder cancer cells. 2018

Jiao Liu, and Jianbin Bi, and Zeliang Li, and Zhenhua Li, and Xiankui Liu, and Chuize Kong
Department of Urology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.

miR‑214 has been reported to be downregulated in several cancer types, such as bladder cancer. However, its involvement in apoptosis and chemoresistance has not been investigated. The present study aimed to clarify the biological function of miR‑214 and potential mechanisms in chemoresistance of bladder cancer cells. Reverse transcription‑quantitative polymerase chain reaction demonstrated that miR‑214 was downregulated in bladder cancer tissues compared with the level in normal tissues. miR‑214 was downregulated in bladder cancer cell lines compared with the level in the normal cell line SV‑HUC‑1. miR‑214 mimics were transfected into T24 and J82 cell lines to restore its expression. The results indicated that miR‑214 mimic inhibited proliferation and invasion in these cell lines. In addition, miR‑214 mimic reduced cisplatin resistance in T24 and J82 cells, indicated by the inhibition of cell viability and upregulation of cell apoptosis. Western blotting demonstrated that miR‑214 mimic was able to upregulate cleaved caspase‑3 and cleaved poly (ADP‑ribose) polymerase (PARP), while downregulate caspase‑3 and PARP expression, and AKT phosphorylation. Using prediction software, it was revealed that the netrin‑1 oncoprotein is on the target list of miR‑214. miR‑214 also downregulated netrin‑1 protein and mRNA expression levels in the T24 and J82 cell lines. Luciferase reporter assays demonstrated that netrin‑1 acted as a direct target of miR‑214. A negative correlation between netrin‑1 and miR‑214 expression in bladder cancer tissues was also observed. In addition, cisplatin treatment could induce netrin‑1 protein expression in bladder cancer cells and miR‑214 mimic partly blocked this phenomenon. Netrin‑1 plasmid transfection inhibited cisplatin‑induced apoptosis, upregulated AKT phosphorylation, and downregulated caspase‑3 and PARP cleavage. Netrin‑1 was restored in cells transfected with miR‑214 mimic using plasmid transfection. Netrin‑1 transfection restored AKT phosphorylation and blocked caspase/PARP cleavage in the T24 and J82 cell lines. In conclusion, the present study demonstrated that miR‑214 is downregulated in bladder cancer tissues and cell lines. miR‑214 reduces chemoresistance by targeting netrin‑1 in bladder cancer cell lines.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009361 Neoplasm Invasiveness Ability of neoplasms to infiltrate and actively destroy surrounding tissue. Invasiveness, Neoplasm,Neoplasm Invasion,Invasion, Neoplasm
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D001749 Urinary Bladder Neoplasms Tumors or cancer of the URINARY BLADDER. Bladder Cancer,Bladder Neoplasms,Cancer of Bladder,Bladder Tumors,Cancer of the Bladder,Malignant Tumor of Urinary Bladder,Neoplasms, Bladder,Urinary Bladder Cancer,Bladder Cancers,Bladder Neoplasm,Bladder Tumor,Cancer, Bladder,Cancer, Urinary Bladder,Neoplasm, Bladder,Neoplasm, Urinary Bladder,Tumor, Bladder,Tumors, Bladder,Urinary Bladder Neoplasm
D002945 Cisplatin An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. Platinum Diamminodichloride,cis-Diamminedichloroplatinum(II),cis-Dichlorodiammineplatinum(II),Biocisplatinum,Dichlorodiammineplatinum,NSC-119875,Platidiam,Platino,Platinol,cis-Diamminedichloroplatinum,cis-Platinum,Diamminodichloride, Platinum,cis Diamminedichloroplatinum,cis Platinum
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000075388 Netrin-1 A netrin that binds the DCC RECEPTOR or UNC5 receptors, resulting respectively in axon attraction or repulsion. Its interaction with these receptors also prevents APOPTOSIS; it may function as a tumor suppressor protein. NTN1 Protein,Netrin-1 Protein,Netrin 1,Netrin 1 Protein,Protein, NTN1,Protein, Netrin-1
D015536 Down-Regulation A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Down-Regulation,Down-Regulation (Physiology),Downregulation,Down Regulation,Down-Regulation, Receptor

Related Publications

Jiao Liu, and Jianbin Bi, and Zeliang Li, and Zhenhua Li, and Xiankui Liu, and Chuize Kong
April 2018, International journal of molecular medicine,
Jiao Liu, and Jianbin Bi, and Zeliang Li, and Zhenhua Li, and Xiankui Liu, and Chuize Kong
October 2018, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie,
Jiao Liu, and Jianbin Bi, and Zeliang Li, and Zhenhua Li, and Xiankui Liu, and Chuize Kong
January 2008, Cancer research,
Jiao Liu, and Jianbin Bi, and Zeliang Li, and Zhenhua Li, and Xiankui Liu, and Chuize Kong
October 2015, Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae,
Jiao Liu, and Jianbin Bi, and Zeliang Li, and Zhenhua Li, and Xiankui Liu, and Chuize Kong
February 2024, Journal of chemotherapy (Florence, Italy),
Jiao Liu, and Jianbin Bi, and Zeliang Li, and Zhenhua Li, and Xiankui Liu, and Chuize Kong
September 2015, Oncotarget,
Jiao Liu, and Jianbin Bi, and Zeliang Li, and Zhenhua Li, and Xiankui Liu, and Chuize Kong
August 2014, Anti-cancer drugs,
Jiao Liu, and Jianbin Bi, and Zeliang Li, and Zhenhua Li, and Xiankui Liu, and Chuize Kong
January 2021, Analytical cellular pathology (Amsterdam),
Jiao Liu, and Jianbin Bi, and Zeliang Li, and Zhenhua Li, and Xiankui Liu, and Chuize Kong
January 2016, International journal of biological sciences,
Jiao Liu, and Jianbin Bi, and Zeliang Li, and Zhenhua Li, and Xiankui Liu, and Chuize Kong
August 2017, Bioscience reports,
Copied contents to your clipboard!