MicroRNA-382-5p aggravates breast cancer progression by regulating the RERG/Ras/ERK signaling axis
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Jar-Yi Ho1,*, Ren-Jun Hsu1,2,3,*, Jui-Ming Liu4, Szu-Chi Chen1, Guo-Shiou Liao5, Hong-Wei Gao1, Cheng-Ping Yu1,2,3
1Department of Pathology, and Graduate Institute of Pathology and Parasitology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
2Biobank Management Center of Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
3Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan
4Division of Urology, Department of Surgery, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan
5Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
*These authors have contributed equally to this work
Cheng-Ping Yu, email: [email protected]
Keywords: miR-382-5p, RERG, Ras/ERK pathway, breast cancer
Received: March 29, 2016 Accepted: September 20, 2016 Published: September 29, 2016
Aberrant activation of the Ras/ERK pathway mediates breast cancer initiation and aggressiveness. Therefore, it is important to identify miRNAs that modulate the Ras/ERK pathway during breast carcinogenesis and progression. The Ras GTPase superfamily member RERG (Ras-related and estrogen-regulated growth inhibitor) acts as a tumor suppressor to reduce breast cancer cell proliferation and tumor formation and has been suggested to have a regulatory role in the Ras/ERK pathway. In this study, we found that RERG exerted its tumor suppressor role by attenuating the activation of Ras/ERK signaling effectors. Furthermore, we found that miR-382-5p directly targets and represses RERG to attenuate the inhibitory effects of RERG on the oncogenic Ras/ERK pathway. Thereby, miR-382-5p promoted breast cancer cell viability, clonogenicity, survival, migration, invasion and in vivo tumorigenesis/metastasis. In clinical interpretation, miR-382-5p expression was negatively correlated with RERG expression, and it also significantly functioned as an independent oncomiR for the higher incidence and poorer prognosis of breast cancer. This novel connection highlights new diagnostic and prognostic roles for miR-382-5p and RERG in breast cancer.
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