Open AccessMiR‐129‐5p promotes docetaxel resistance in prostate cancer by down‐regulating CAMK2N1 expression
Author(s) -
Wu Cheng,
Miao Chunqing,
Tang Qingsheng,
Zhou Xunrong,
Xi Pengshan,
Chang Ping'an,
Hua Lixin,
Ni Haodong
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14050
Subject(s) - docetaxel , apoptosis , cancer research , flow cytometry , cancer cell , transfection , prostate cancer , chemistry , cell culture , cancer , biology , microbiology and biotechnology , medicine , genetics , biochemistry
This study focuses on the effect of miR‐129‐5p on docetaxel‐resistant ( DR ) prostate cancer ( PC a) cells invasion, migration and apoptosis. In our study, the expression of CAMK 2N1 was assessed by qRT ‐ PCR in PC a patient tissues and cell lines including PC ‐3 and PC ‐3‐ DR . Cells transfected with miR‐129‐5p mimics, inhibitor, CAMK 2N1 or negative controls ( NC ) were used to interrogate their effects on DR cell invasions, migrations and apoptosis during docetaxel ( DTX ) treatments. The apoptosis rate of the PC a cells was validated by flow cytometry. Relationships between miR‐129‐5p and CAMK 2N1 levels were identified by qRT ‐ PCR and dual‐luciferase reporter assay. CAMK 2N1 was found to be down‐expressed in DR PC a tissue sample, and low levels of CAMK 2N1 were correlated with high docetaxel resistance and clinical prediction of poor survival. CAMK 2N1 levels were decreased in DR PC a cells treated with DXT . We further explored that up‐regulation of miR‐129‐5p could promote DR PC a cells viability, invasion and migration but demote apoptosis. Involved molecular mechanism studies revealed that miR‐129‐5p reduced downstream CAMK 2N1 expression to further impact on chemoresistance to docetaxel of PC a cells, indicating its vital role in PC a docetaxel resistance. Our findings revealed that miR‐129‐5p contributed to the resistance of PC ‐3‐ DR cells to docetaxel through suppressing CAMK 2N1 expression, and thus targeting miR‐129‐5p may provide a novel therapeutic approach in sensitizing PC a to future docetaxel treatment.