Chen Guanglei, Sun Lisha, Han Jianjun, Shi Sufang, Dai Yuna, Liu Weiguang
Department of Breast Surgery, Shengjing Hospital of China Medical University Shenyang 110004, Liaoning Province, China.
Department of Breast Surgery, Affiliated Hospital of Hebei University of Engineering Handan 056000, Hebei Province, China.
Am J Cancer Res. 2019 Aug 1;9(8):1583-1606. eCollection 2019.
Breast cancer (BC) is the most common malignancy in women and is one of the leading causes of cancer-associated deaths. The analysis of data obtained from online databases revealed that RILPL2 expression in BC tissues is lower than that in normal tissues, and that RILPL2 upregulation is correlated with prolonged recurrence-free survival (RFS), overall survival (OS), and distant metastasis-free survival (DMFS). However, the function of RILPL2 in tumor proliferation and metastasis remains unclear. In this study, we demonstrated that RILPL2 had lower expression in BC tissues than in adjacent normal tissues, and that RILPL2 expression was significantly negatively correlated with tumor size, histological grade, and lymph node metastasis. Univariate analysis showed a positive correlation between RILPL2 and estrogen receptor (ER) expression and a negative correlation between RILPL2 and human epidermal growth factor receptor 2 (HER2) expression. Overexpression of RILPL2 inhibited BC cell proliferation and metastasis and . In addition, the interaction of exogenous RILPL2 with TUBB3 resulted in the downregulation of BC cell proliferation and migration and upregulation of PTEN expression by promoting destabilization of TUBB3. Furthermore, RILPL2 could reverse BC cell resistance to taxotere-mediated apoptosis by regulating the TUBB3/PTEN/AKT pathway. In conclusion, these results suggest that RILPL2 could be a novel biomarker for the diagnosis and treatment of BC.
乳腺癌（BC）是女性中最常见的恶性肿瘤，也是癌症相关死亡的主要原因之一。对从在线数据库获得的数据进行分析后发现，BC组织中RILPL2的表达低于正常组织，且RILPL2的上调与无复发生存期（RFS）延长、总生存期（OS）和无远处转移生存期（DMFS）相关。然而，RILPL2在肿瘤增殖和转移中的功能仍不清楚。在本研究中，我们证明RILPL2在BC组织中的表达低于相邻正常组织，且RILPL2表达与肿瘤大小、组织学分级和淋巴结转移显著负相关。单因素分析显示RILPL2与雌激素受体（ER）表达呈正相关，与人类表皮生长因子受体2（HER2）表达呈负相关。RILPL2的过表达抑制了BC细胞的增殖和转移。此外，外源性RILPL2与TUBB3的相互作用通过促进TUBB3的不稳定导致BC细胞增殖和迁移下调以及PTEN表达上调。此外，RILPL2可通过调节TUBB3/PTEN/AKT途径逆转BC细胞对多西他赛介导的凋亡的抗性。总之，这些结果表明RILPL2可能是BC诊断和治疗的一种新型生物标志物。
