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LncRNA AFAP1-AS1 modulates the sensitivity of paclitaxel-resistant prostate cancer cells to paclitaxel via miR-195-5p/FKBP1A axis.

Authors
  • Leng, Weiping1
  • Liu, Qingzuo2
  • Zhang, Shidong3
  • Sun, Dekang2
  • Guo, Yongshun3
  • 1 Department of Pharmacy, Yantaishan Hospital , Yantai, Shandong, China. , (China)
  • 2 Department of Urology, Yantai Yuhuangding Hospital , Yantai, Shandong, China. , (China)
  • 3 Department of Urology, Weifang People's Hospital , Weifang, Shandong, China. , (China)
Type
Published Article
Journal
Cancer Biology & Therapy
Publisher
Landes Bioscience
Publication Date
Nov 01, 2020
Volume
21
Issue
11
Pages
1072–1080
Identifiers
DOI: 10.1080/15384047.2020.1829266
PMID: 33138677
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

LncRNA AFAP1-AS1 has been corroborated to function in diverse cancers. Our aim was to investigate the molecular mechanism of AFAP1-AS1 in PTX resistance in PCa. The levels of AFAP1-AS1, miR-195-5p, and FKBP1A were checked by qRT-PCR. 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium Bromide (MTT) assay was employed to assess the resistance of PTX-resistant PCa cells to PTX. Flow cytometry was introduced to evaluate cell apoptosis. The protein levels of C-caspase 3 were determined by western blot. The starBase was used to predict the interaction between miR-195-5p and AFAP1-AS1. Xenograft tumor model was established to investigate the biological role of AFAP1-AS1 in PTX resistance in vivo. The levels of AFAP1-AS1 and FKBP1A were upregulated in PCa tissues and cells, as well as PTX-resistant PCa cells, while the expression of miR-195-5p was declined. Knockdown of AFAP1-AS1 promoted the sensitivity of PTX-resistant PCa cells to PTX, induced apoptosis of PTX-resistant PCa cells, whereas the impacts could be reversed by reducing the expression of miR-195-5p. FKBP1A overexpression could rescue the effects of miR-195-5p-mediated enhancement on the sensitivity of PTX-resistant PCa cells to PTX, promotion on apoptosis of PTX-resistant PCa cells. AFAP1-AS1 interacted with miR-195-5p and miR-195-5p could bind to the 3'UTR of FKBP1A. AFAP1-AS1 silencing inhibited the tumor growth in mice implanted with PC3-TXR cell. The protein level of PCNA was decreased in PC3-TXR cells transfected with sh-AFAP1-AS1, while the expression of C-caspase 3 was upregulated. AFAP1-AS1 silencing attenuated the resistance of PTX-resistant PCa cells to PTX by downregulating FKBP1A via sponging miR-195-5p.

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