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

• Published in: Cancer medicine (Malden, MA) MA), 2018-05, Vol.7 (5), p.1988-2002
• Main Authors: Arai, Takayuki, Okato, Atsushi, Yamada, Yasutaka, Sugawara, Sho, Kurozumi, Akira, Kojima, Satoko, Yamazaki, Kazuto, Naya, Yukio, Ichikawa, Tomohiko, Seki, Naohiko
• Format: Article
• Language: English
• Subjects: Aged; Base Sequence; Cancer; Cancer Biology; Castration; Castration‐resistant prostate cancer; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Condensin; Down-Regulation - genetics; Ectopic expression; Gene Expression Regulation, Neoplastic - genetics; Humans; Male; microRNA; MicroRNAs - genetics; Middle Aged; miRNA; miR‐99a‐3p; miR‐99a‐5p; Neoplasm Invasiveness - genetics; non‐SMC condensin I complex subunit G; Original Research; Pathogenesis; Prostate cancer; Prostatic Neoplasms, Castration-Resistant - genetics; Prostatic Neoplasms, Castration-Resistant - pathology; RNA Interference; RNA, Small Interfering - genetics; Sequence Analysis, RNA; Therapeutic applications
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.1455

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. 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.