Hsa_circ_0005221 promotes prostate cancer progression through the miR-339-5p/STAT5a pathway

OBJECTIVE: To investigate the molecular mechanism of hsa_circ_0005221 regulating the progression of PCa through the miR-339-5p/STAT5a pathway.

METHODS: Localizations of hsa_circ_0005221 and miR-339-5p in cells were detected by nuclear-cytoplasmic isolation. MiRNA-339-5p was selected as the target miRNA bound to hsa_circ_0005221 by RNA pull-down assay. The binding site of the luciferase reporter gene was predicted by software and the binding capability of miR-339-5p validated by luciferase assay. The expression of hsa_circ_0005221 in the prostatic epithelial and PCa cells was determined by qPCR. The hsa_circ_0005221-overexpressed plasmid and siRNA were transfected into the PCa cells for measurement of their proliferation, invasion and migration abilities and the levels of epithelial-mesenchymal transformation (EMT) and apoptosis. After knockdown of hsa_circ_0005221 and transfection of miR-339-5p mimics and miR-339-5p inhibitor, the proliferation, invasion and migration abilities of the DU145 and LNCaP cells were detected, and so were the levels of the EMT signature protein, STAT5a and cell apoptosis.

RESULTS: The expression of hsa_circ_0005221 was significantly higher in the PCa than in the prostatic epithelial cells. Nuclear-cytoplasmic isolation experiments showed that hsa_circ_0005221 and miR-339-5p were mainly located in the cytoplasm. The proliferation, invasion and migration abilities and EMT were decreased and the apoptosis increased in the DU145 and LNCaP cells with knockdown of hsa_circ_0005221, which was just the reverse in those with overexpressed hsa_circ_0005221. Among the top 5 miRNAs predicted by software, miR-339-5p, miR-17 and miR-520h were shown by pull-down assay to be bound to hsa_circ_0005221, with most obvious changes in miR-339-5p when hsa_circ_0005221 knocked down or overexpressed. Luciferase reporter gene assay showed the binding of hsa_circ_0005221 to miR-339-5p. Knockdown of hsa_circ_0005221 and transfection of miR-339-5p mimics into the DU145 and LNCaP cells significantly reduced the proliferation, invasion and migration abilities of the cells and the N-cad level, increased their apoptosis and E-cad level, and up-regulated the expression of STAT5a, while overexpression of hsa_circ_0005221 and transfection of miR-339-5p mimics induced just the opposite effects.

CONCLUSIONS: Hsa_circ_0005221 enhances the progression of prostate cancer through the miR-339-5p/STAT5a pathway.

Medienart:

Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:27

Enthalten in:

Zhonghua nan ke xue = National journal of andrology - 27(2021), 4 vom: 07. Apr., Seite 301-308

Sprache:

Chinesisch

Beteiligte Personen:

Chen, Sai-Sai [VerfasserIn]
Zhang, Yu-Wei [VerfasserIn]
Wang, Ya-Li [VerfasserIn]
Gao, Yue [VerfasserIn]
Wang, Can [VerfasserIn]
Hu, Qiang [VerfasserIn]
Wu, Tian-Ge [VerfasserIn]
Tao, Shu-Chun [VerfasserIn]
Zhao, Jian-Xin [VerfasserIn]
Chen, Ming [VerfasserIn]

Themen:

Hsa_circ_0005221
Journal Article
MIRN339 microRNA, human
MiR-339-5p
MicroRNAs
Prostate cancer
RNA, Circular
RNA, Small Interfering
STAT5 Transcription Factor
STAT5A protein, human
STAT5a
Tumor Suppressor Proteins

Anmerkungen:

Date Completed 20.12.2021

Date Revised 31.05.2022

published: Print

Citation Status MEDLINE

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM334504287