Open AccessGli2 mediates the development of castration‑resistant prostate cancer
Author(s) -
Lu Xia,
Hakim Bouamar,
Xiang Gu,
Carla Zeballos,
Tai Qin,
Bingzhi Wang,
You Zhou,
Yuhui Wang,
Junhua Yang,
Haiyan Zhu,
Weishe Zhang,
Peter J. Houghton,
LuZhe Sun
Publication year - 2020
Publication title -
international journal of oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.405
H-Index - 122
ISSN - 1019-6439
DOI - 10.3892/ijo.2020.5044
Subject(s) - lncap , prostate cancer , cancer research , oncogene , gli2 , gene knockdown , biology , cell cycle , cancer , molecular medicine , hedgehog signaling pathway , medicine , apoptosis , microbiology and biotechnology , signal transduction , genetics
Glioma‑associated oncogene family zinc finger 2 (Gli2), a key component of the hedgehog signaling pathway, has been previously demonstrated to promote the malignant properties of prostate cancer in vitro. However, the role of Gli2 in the development of castration‑resistant prostate cancer (CRPC) has yet to be fully elucidated. In the present study, Gli2 expression was knocked down in androgen‑responsive prostate cancer cells using an inducible Gli2 short hairpin RNA. Suppression of Gli2 expression resulted in significant reduction of cell viability, increased the proportion of cells in the G0/G1 phases of the cell cycle and reduced the expression of genes associated with cell cycle progression. Gli2 knockdown sensitized both androgen‑dependent and ‑independent prostate cancer cells to the antiandrogen drug Casodex and prevented the outgrowth of LNCaP prostate cancer cells. In addition, Gli2 knockdown significantly suppressed the development of CRPC in a LNCaP xenograft mouse model, which was reversed by the re‑expression of Gli2. In conclusion, to the best of our knowledge, the present study was the first occasion in which the essential role of Gli2 in the development of CRPC was demonstrated, providing a potential therapeutic target for the intervention of CRPC.