PIWI-interacting RNA-36712 restrains breast cancer progression and chemoresistance by interaction with SEPW1 pseudogene SEPW1P RNA

Molecular Cancer

Bailin Zhang¹  Jie Yang²  Wen Tan²  Mei Li³  Xiaobing Jiang⁴  Jiachun Su⁵  Ling Pan⁵  Dongxin Lin⁵  Liping Tan⁵  Ruihong Bai⁵  Zexian Liu⁵  Qi Zhao⁵  Xiaoxing Li⁵  Jian Zheng⁵  Dongmei Mai⁵  Jialiang Zhang⁵  Xudong Huang⁵  Ying Ye⁵  Yanfen Zheng⁵  Zhixiang Zuo⁵ 

[1] Department of Breast Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College;Department of Etiology and Carcinogenesis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College;Department of Pathology, Sun Yat-sen University Cancer Center;Department of Surgical Oncology, Sun Yat-sen University Cancer Center;State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center;

关键词: piRNA;    Breast cancer;    P53;    Drug sensitivity;    SEPW1;   

DOI  :  10.1186/s12943-019-0940-3

来源: DOAJ

【 摘 要 】

Abstract Background Breast cancer is one of the most common malignancies and the major cause of cancer-related death in women. Although the importance of PIWI-interacting RNAs (piRNAs) in cancer has been increasingly recognized, few studies have been explored the functional mechanism of piRNAs in breast cancer development and progression. Methods We examined the top 20 highly expressed piRNAs based on the analysis of TCGA breast cancer data in two patient cohorts to test the roles of piRNAs in breast cancer. The effects of piRNA-36,712 on the malignant phenotypes and chemosensitivity of breast cancer cells were detected in vitro and in vivo. MS2-RIP and reporter gene assays were conducted to identify the interaction and regulation among piRNA-36,712, miRNAs and SEPW1P. Kaplan-Meier estimate with log-rank test was used to compare patient survival by different piRNA-36,712 expression levels. Results We found piRNA-36,712 level was significantly lower in breast cancer than in normal breast tissues and low level was correlated with poor clinical outcome in patients. Functional studies demonstrated that piRNA-36,712 interacts with RNAs produced by SEPW1P, a retroprocessed pseudogene of SEPW1, and subsequently inhibits SEPW1 expression through competition of SEPW1 mRNA with SEPW1P RNA for microRNA-7 and microRNA-324. We also found that higher SEPW1 expression due to downregulation of piRNA-36,712 in breast cancer may suppress P53, leading to the upregulated Slug but decreased P21 and E-cadherin levels, thus promoting cancer cell proliferation, invasion and migration. Furthermore, we found that piRNA-36,712 had synergistic anticancer effects with the paclitaxel and doxorubicin, two chemotherapeutic agents for breast cancer. Conclusions These findings suggest that piRNA-36,712 is a novel tumor suppressor and may serve as a potential predictor for the prognosis of breast cancer patients.

【 授权许可】

Unknown