J Cancer 2020; 11(12):3645-3654. doi:10.7150/jca.39463

Research Paper

LncRNA NONHSAT141924 promotes paclitaxel chemotherapy resistance through p-CREB/Bcl-2 apoptosis signaling pathway in breast cancer

Ming Gu1, Wenhui Zheng2, Mingdi Zhang3, Xiaoshen Dong1, Yan Zhao1, Shuo Wang1, Haiyang Jiang1, Xinyu Zheng1,4✉

1. Department of Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, People's Republic of China
2. Department of anesthesiology, The Shengjing Hospital of China Medical University, Shenyang, Liaoning 110001, People's Republic of China
3. Department of Breast Surgery, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, People's Republic of China
4. Lab 1, Cancer Institute, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, People's Republic of China

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Citation:
Gu M, Zheng W, Zhang M, Dong X, Zhao Y, Wang S, Jiang H, Zheng X. LncRNA NONHSAT141924 promotes paclitaxel chemotherapy resistance through p-CREB/Bcl-2 apoptosis signaling pathway in breast cancer. J Cancer 2020; 11(12):3645-3654. doi:10.7150/jca.39463. Available from http://www.jcancer.org/v11p3645.htm

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Abstract

Breast cancer is the most prevalent malignant neoplasm among women worldwide. Despite continuous improvement of breast cancer individualized comprehensive therapy, local recurrence and distant metastasis still remain the challenges due to the development of acquired drug-resistance. Long non-coding RNAs (LncRNAs) is known to participated in the development of breast cancer. However, the mechanisms of LncRNAs involving in drug-resistance of breast cancer during chemotherapy remain to be further elucidated. Aiming to screen for candidate LncRNAs responsible for breast cancer mechanism, we first investigated the expression patterns of LncRNAs and mRNAs in paired breast cancer tissues and normal tissues using Agilent Human lncRNA array. The microarray results clearly demonstrated multiple differentially expressed mRNAs and LncRNAs including LncRNA NONHSAT141924. The remarkable up-regulation of LncRNA NONHSAT141924 in breast cancer MCF-7 was further confirmed by quantitative real-time PCR. GO and KEGG pathway analysis demonstrated that LncRNA NONHSAT141924 was most closely associated with paclitaxel (PTX)-resistant phenotype. To further explore the mechanism by which LncRNA NONHSAT141924 contributes to PTX-resistant characteristics, LncRNA NONHSAT141924 was transfected into MCF-7 breast cancer cell line. Overexpression of LncRNA NONHSAT141924 significantly reduced MCF-7 cell survivability through modulation of p-CREB/Bcl-2 apoptosis signaling pathway, one of the major pathways participated in LncRNAs-mediated chemotherapy resistance. Taken together, our study provides a new LncRNA-mediated regulatory mechanism for PTX-resistance of breast cancer and suggests that therapeutic inhibition of LncRNA NONHSAT141924 might be an efficient strategy for PTX-resistant breast cancer treatment.

Keywords: LncRNA, paclitaxel-resistance, p-CREB/Bcl-2 apoptosis signaling pathway, breast cancer