miR-93/miR-106b/miR-375-CIC-CRABP1: a novel regulatory axis in prostate cancer progression.
miR-93/miR-106b/miR-375-CIC-CRABP1: a novel regulatory axis in prostate cancer progression.
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DOI：
10.18632/oncotarget.4372
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发表时间：
2015-09-15
期刊：
影响因子：
--
通讯作者：
Lee Y
中科院分区：
文献类型：
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作者：
Choi N;Park J;Lee JS;Yoe J;Park GY;Kim E;Jeon H;Cho YM;Roh TY;Lee Y
Capicua（CIC）与脊髓小脑共济失调1型（SCA 1）神经退行性疾病和某些类型的癌症的发病机制有关;然而，CIC在前列腺癌中的作用仍然未知。在这里，我们表明，CIC抑制前列腺癌的进展。CIC在前列腺癌中的表达明显降低。CIC过表达抑制前列腺癌细胞增殖、侵袭和迁移，而CIC RNAi发挥相反的作用。我们发现，敲低CIC分别在LNCaP和PC-3细胞中去抑制ETV 5和CRABP 1的表达，从而促进细胞增殖和侵袭。我们还发现，已知在前列腺癌患者中频繁过表达的miR-93、miR-106 b和miR-375协同下调CIC水平以促进癌症进展。总之，我们认为miR-93/miR-106 b/miR-375-CIC-CRABP 1是前列腺癌进展的一个新的关键调控轴。
Capicua (CIC) has been implicated in pathogenesis of spinocerebellar ataxia type-1 (SCA1) neurodegenerative disease and some types of cancer; however, the role of CIC in prostate cancer remains unknown. Here we show that CIC suppresses prostate cancer progression. CIC expression was markedly decreased in human prostatic carcinoma. CIC overexpression suppressed prostate cancer cell proliferation, invasion, and migration, whereas CIC RNAi exerted opposite effects. We found that knock-down of CIC derepresses expression of ETV5 and CRABP1 in LNCaP and PC-3 cells, respectively, thereby promoting cell proliferation and invasion. We also discovered that miR-93, miR-106b, and miR-375, which are known to be frequently overexpressed in prostate cancer patients, cooperatively down-regulate CIC levels to promote cancer progression. Altogether, we suggest miR-93/miR-106b/miR-375-CIC-CRABP1 as a novel key regulatory axis in prostate cancer progression.