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. 2025 Jul 22.
doi: 10.1111/cas.70157. Online ahead of print.

Androgen Receptor-Controlled microRNA-124-3p.2 Suppresses Prostate Cancer Progression via CCL2 Inhibition

Shuhei Aoyama  1 , Kouji Izumi  1 , Kaoru Hiratsuka  1 , Takahiro Inaba  1 , Yoshiki Koketsu  1 , Ryunosuke Nakagawa  1 , Ren Toriumi  1 , Taiki Kamijima  1 , Hiroshi Kano  1 , Tomoyuki Makino  1 , Renato Naito  1 , Suguru Kadomoto  1 , Hiroaki Iwamoto  1 , Hiroshi Yaegashi  1 , Shohei Kawaguchi  1 , Kazuyoshi Shigehara  1 , Takahiro Nohara  1 , Hiroki Nakata  2 , Yohei Saito  3 , Kyoko Nakagawa-Goto  3 , Wen-Jye Lin  4 , Atsushi Mizokami  1
Affiliations

Androgen Receptor-Controlled microRNA-124-3p.2 Suppresses Prostate Cancer Progression via CCL2 Inhibition

Shuhei Aoyama et al. Cancer Sci. .

Abstract

We previously reported that androgen receptor (AR) signaling blockade induces chemotactic-C-C-motif-chemokine-ligand-2 (CCL2) secretion from prostate cancer cells and activates cancer cells through an autocrine manner. However, the mechanism of how AR negatively regulates CCL2 expression is still unclear. As various microRNAs participate in prostate cancer development, we hypothesized that there are AR-controlled miRs that regulate CCL2 production. Using LNCaP and C4-2B cells, miR-124-3p.2 was found as a potential miR from the miRNA PCR array and public database. The expression of miR-124-3p.2 was inhibited by knockdown AR, and the introduction of miR-124-3p.2 mimic decreased CCL2 expression and suppressed cell migration. Dihydrotestosterone led to miR-124-3p.2 upregulation and CCL2 downregulation. To examine whether miR-124-3p.2 and CCL2 are involved in prostate cancer progression, their expression levels and clinical parameters were analyzed using prostate biopsy samples and whole blood RNAs obtained from the biopsied patients. Patients with low miR-124-3p.2 and high CCL2 levels showed a shorter time to castration-resistant prostate cancer development than those with high miR-124-3p.2 and low CCL2 levels. Our study demonstrated that AR suppresses CCL2 expression via miR-124-3p.2, and the miR-124-3p.2-CCL2 axis may be a novel therapeutic target and a useful blood prognostic biomarker for advanced prostate cancer.

Keywords: CCL2; androgen receptor; castration‐resistant prostate cancer; microRNA; whole blood RNA.

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