Li Zhenghu, Ling Zhi-Qiang, Guo Weiwei, Lu Xiao-Xiao, Pan Yi, Wang Zhenzhen, Chen Yan
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, China.
Oncotarget. 2015 May 20;6(14):12357-68. doi: 10.18632/oncotarget.3657.
PAQR3 is a newly discovered tumor suppressor and its functional role in breast cancer has not been well characterized. We report here that PAQR3 is associated with the progression and survival of human patients with breast cancer, as well as cell proliferation and migration of human breast cancer cells. PAQR3 mRNA level was robustly downregulated in human breast cancer samples compared with their corresponding para-cancerous histological normal tissues (n = 82, P < 0.0001). The mRNA level of PAQR3 was negatively correlated with HER2 expression (P < 0.0001) and disease-free survival of the patients (P < 0.0001). PAQR3 overexpression inhibited cell proliferation, colony formation and migration of breast cancer cells including MCF7, SKBR3, MDA-MD-231, MDA-MD-468 and MDA-MD-453 cells. Knockdown of PAQR3 in MDA-MD-231 cells elevated cell proliferation and migration. Inhibition of HER2 by trastuzumab increased PAQR3 expression in SKBR3 cells. In conclusion, PAQR3 expression is frequently downregulated in human breast cancers inversely correlated with HER2 expression. PAQR3 is able to modulate the proliferation and migration of breast cancer cells. Our data indicate that PAQR3 functions as a tumor suppressor in the development of human breast cancers.
PAQR3是一种新发现的肿瘤抑制因子，其在乳腺癌中的功能作用尚未得到充分阐明。我们在此报告，PAQR3与人类乳腺癌患者的病情进展和生存情况相关，也与人类乳腺癌细胞的增殖和迁移有关。与相应的癌旁组织学正常组织相比，PAQR3 mRNA水平在人类乳腺癌样本中显著下调（n = 82，P < 0.0001）。PAQR3的mRNA水平与HER2表达呈负相关（P < 0.0001），与患者的无病生存期也呈负相关（P < 0.0001）。PAQR3过表达抑制了包括MCF7、SKBR3、MDA-MD-231、MDA-MD-468和MDA-MD-453细胞在内的乳腺癌细胞的增殖、集落形成和迁移。在MDA-MD-231细胞中敲低PAQR3可提高细胞增殖和迁移能力。曲妥珠单抗抑制HER2可增加SKBR3细胞中PAQR3的表达。总之，PAQR3表达在人类乳腺癌中经常下调，与HER2表达呈负相关。PAQR3能够调节乳腺癌细胞的增殖和迁移。我们的数据表明，PAQR3在人类乳腺癌发生发展中起肿瘤抑制作用。
