Research Papers:

LncRNA H19 confers chemoresistance in ERα-positive breast cancer through epigenetic silencing of the pro-apoptotic gene BIK

Xinxin Si, Ruochen Zang, Erbao Zhang, Yue Liu, Xiao Shi, Ershao Zhang, Lipei Shao, Andi Li, Nan Yang, Xiao Han, Beijing Pan, Zhihong Zhang, Luan Sun and Yujie Sun _

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Oncotarget. 2016; 7:81452-81462. https://doi.org/10.18632/oncotarget.13263

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Xinxin Si1,4, Ruochen Zang1,4, Erbao Zhang5, Yue Liu1,4, Xiao Shi1,4, Ershao Zhang1,4, Lipei Shao1,4, Andi Li1,4, Nan Yang1,5, Xiao Han1,5, Beijing Pan6, Zhihong Zhang6, Luan Sun1,4, Yujie Sun1,2,3,4

1Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu, China

2Collaborative Innovation Center for Cancer Medicine, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Nanjing Medical University, Nanjing, Jiangsu, China

3State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China

4Department of Cell Biology, Nanjing Medical University, Nanjing, Jiangsu, China

5Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, China

6Department of Pathology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

Correspondence to:

Yujie Sun, email: [email protected]

Luan Sun, email: [email protected]

Keywords: breast cancer, chemoresistance, lncRNA H19, apoptosis, estrogen receptor

Received: May 01, 2016     Accepted: October 21, 2016     Published: November 10, 2016


Breast cancer is a common malignancy in women. Acquisition of drug resistance is one of the main obstacles encountered in breast cancer therapy. Long non-coding RNA (lncRNA) has been demonstrated to play vital roles in both development and tumorigenesis. However, the relationship between lncRNAs and the development of chemoresistance is not well established. In the present study, the high expression of lncRNA H19 was identified as a powerful factor associated with paclitaxel (PTX) resistance in ERα-positive breast cancer cells, but not in ERα-negative breast cancer cells. LncRNA H19 attenuated cell apoptosis in response to PTX treatment by inhibiting transcription of pro-apoptotic genes BIK and NOXA. H19 was further confirmed to suppress the promoter activity of BIK by recruiting EZH2 and by trimethylating the histone H3 at lysine 27. Interestingly, our data showed that lncRNA H19 was one of the downstream target molecules of ERα. Altered ERα expression may therefore change H19 levels to modulate the apoptosis response to chemotherapy in breast cancer cells. Our data suggest that the ERα-H19-BIK signaling axis plays an important role in promoting chemoresistance.

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