Premium
Rs6265 polymorphism in brain‐derived neurotrophic factor (Val/Val and Val/Met) promotes proliferation of bladder cancer cells by suppressing microRNA‐205 and enhancing expression of cyclin J
Author(s) -
Zhang Jin,
Song Ni,
Duan Zhongqi
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.28004
Subject(s) - rs6265 , brain derived neurotrophic factor , neurotrophic factors , microrna , microbiology and biotechnology , western blot , gene expression , medicine , biology , chemistry , endocrinology , gene , genetics , receptor
Background In this study, we evaluated the effect of rs6265 polymorphism on the expression of brain‐derived neurotrophic factor (BDNF) and relevant downstream targets, as well as the involvement of this polymorphism in bladder cancer. Method A computational analysis and luciferase assays were used to explore the interaction among BDNF, miR‐205, and cyclin J (CCNJ). Real‐time polymerase chain reaction (RT‐PCR) and Western blot analysis were carried out to determine the effect of rs6265 polymorphism on the expression of BDNF and relevant downstream genes. Result BDNF directly inhibited miR‐205 expression but enhanced the expression of CCNJ, which was identified as a virtual target gene of miR‐205. Furthermore, the inhibitory effect of BDNF carrying the Val genotype, defined as BDNF (Val), on miR‐205 expression was much stronger than that of BDNF (Met), while the inductive effect of BDNF (Val) on CCNJ expression was much weaker than that of BDNF (Met). miR‐205 and CCNJ small interfering RNA (siRNA) were found to reduce cell proliferation and arrest the cells in G0/G1 phase. In addition, miR‐205 expression in patients carrying BDNF genotyped as Met/Met (defined as Met/Met group) was much higher than patients carrying BDNF genotyped as Val/Val and Val/Met (defined as Val/Val group and Val/Met group). As an inhibitor of CCNJ expression, the inhibitory effect of miR‐205 was much higher in the Met/Met group than that in the Val/Val and Val/Met groups. Conclusion In summary, we suggested that the rs6265 polymorphism in BDNF upregulates the expression of CCNJ in bladder cancer via the inhibition of miR‐205 expression, which leads to the promoted proliferation of bladder cancer cells.