Regulation of NCAPG by miR-99a-3p (passenger strand) inhibits cancer cell aggressiveness and is involved in CRPC.

Regulation of NCAPG by miR-99a-3p (passenger strand) inhibits cancer cell aggressiveness and is involved in CRPC.
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DOI:
10.1002/cam4.1455
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发表时间:
2018-05
期刊:
影响因子:
4
通讯作者:
Seki N
Seki N
中科院分区:
医学3区
文献类型:
--
作者:
Arai T;Okato A;Yamada Y;Sugawara S;Kurozumi A;Kojima S;Yamazaki K;Naya Y;Ichikawa T;Seki N

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尚未建立针对去势抵抗性前列腺癌(CRPC)患者的有效治疗方法。需要新的方法来识别 CRPC 的假定治疗靶点。对 microRNA (miRNA) 表达的 RNA 测序分析表明,miR-99a-3p(过客链)在多种类型的癌症中显着下调。在这里,我们的目的是确定新的 miR-99a-3p 调控网络和 CRPC 的治疗靶点。 miR-99a-3p 的异位表达显着抑制 PCa 细胞中癌细胞的增殖、迁移和侵袭。非 SMC 凝缩蛋白 I 复合物亚基 G (NCAPG) 是 PCa 细胞中 miR-99a-3p 的直接靶标。在 CRPC 临床标本中检测到 NCAPG 过度表达,并且与较短的无病生存期和晚期临床分期显着相关。 NCAPG 的敲低抑制了癌细胞的侵袭性。过客链 miR-99a-3p 在初始 PCa 和 CRPC 中充当抗肿瘤 miRNA。 NCAPG 受 miR-99a-3p 调控,其过表达参与 CRPC 发病机制。 miRNA 过客链参与癌症发病机制是一个新概念,鉴定 CRPC 中的抗肿瘤 miRNA 调控网络可能会为该疾病提供新的预后标志物和治疗靶点。
Effective treatments for patients with castration‐resistant prostate cancer (CRPC) have not yet been established. Novel approaches for identification of putative therapeutic targets for CRPC are needed. Analyses of RNA sequencing of microRNA (miRNA) expression revealed that miR‐99a‐3p (passenger strand) is significantly downregulated in several types of cancers. Here, we aimed to identify novel miR‐99a‐3p regulatory networks and therapeutic targets for CRPC. Ectopic expression of miR‐99a‐3p significantly inhibited cancer cell proliferation, migration, and invasion in PCa cells. Non‐SMC condensin I complex subunit G (NCAPG) was a direct target of miR‐99a‐3p in PCa cells. Overexpression of NCAPG was detected in CRPC clinical specimens and was significantly associated with shorter disease‐free survival and advanced clinical stage. Knockdown of NCAPG inhibited cancer cell aggressiveness. The passenger strand miR‐99a‐3p acted as an antitumor miRNA in naïve PCa and CRPC. NCAPG was regulated by miR‐99a‐3p, and its overexpression was involved in CRPC pathogenesis. Involvement of passenger strand of miRNA in cancer pathogenesis is novel concept, and identification of antitumor miRNA regulatory networks in CRPC might be provided novel prognostic markers and therapeutic targets for this disease.
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